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Utskriftsdato (24.3.2017)

Gestational Trophoblastic Disease

/upload/trofoblastsykdom/trofoblast.gifTrophoblastic cells constitute the outer layer of an embryo.

Trophoblastic diseases originate during pregnancy, and consequently contain genetic material, which is foreign for the woman. The disease can occur after normal pregnancy, ectopic pregnancy, as well as spontaneous and induced abortion. 

During fertilization, trophoblastic cells invade the endometrium, blood vessels and myometrium to establish fetomaternal circulation.  In a normal pregnancy, a large number of trophoblasts circulate in the mother's blood system. In trophoblastic diseases, there is uninhibited invasion of trophoblasts in the mother's myometrium and blood system.

Trophoblastic diseases are separated into:

Premalign:

  • Complete hydatidiform mole
  • Partial hydatidiform mole

Malignant:

  • Persistent trophoblastic disease/Invasive mole
  • Choriocarcinoma
  • Placental-site trophoblastic tumor
  • Epithelioid trophoblastic tumor

Incidence 

Incidence in Norway (1):

  • Invasive persistent mole occurs in 0.9 cases per 1000 births, and constitutes about 50 cases per year.
  • Choriocarcinoma occurs in 0.2 cases per 1000 births.
  • Placenta-site trophoblastic tumor occurs once per 500,000 births, and equals about 1 case per 10 years.

The incidence of trophoblastic diseases is higher in China and southeast Asia and occurs in 3 cases per 1000 births (2).  

Etiology of gestational trophoblastic disease

The cause is unknown in most cases, but development of trophoblastic disease is observed in association with earlier occurrence of hydatidiform mole. The risk for a recurrent mole is 0.6–2%.

Histology of gestational trophoblastic disease

Mola hydatidosa is an abnormal pregnancy of paternal origin that is divided into the following entities (according to WHO):

Benign

  • Complete hydatidiform mole – genetically diploid, both chromosome sets are from the father. The complete mole lacks embryo and membranes. The placental tissue is completely changed and consists of large chorionic villi, and hyperplastic trophoblasts, that produce vesicles.
  • Partial hydatidiform mole – often genetically triploid with two chromosomal sets from the father and one from the mother. There is often an embryo with malformations that dies early in the pregnancy. The placental changes are focal and less pronounced compared to a complete mole.

Microscopically it can be difficult to separate complete from partial mole. In addition degenerative changes in the placenta can simulate these conditions.  In complete mole chorionic villi demonstrates hydropic swelling and central cisternas, and a general growth of trophoblasts on the surface of the chorionic villi. Partial mole often shows two populations of chorionic villi, one with ordinary and the other with hydropic villi. Also in the partial mole there is trophoblast proliferation. In addition indentations into the surface of the chorionic villi are seen and it can look like "Norwegian fjords". Embryonic tissue can sometimes appear in partial mole. The microscopic diagnosis requires experience and often additional methods such as immunohistochemistry (p75 kip2), DNA ploidy or molecular methods

Malignant

Photomicrograph demonstrating a choriocarcinoma. Click to enlarge.
  • Persistent trophoblastic disease – after evacuation of a mola hydatidosa serum hCG will  spontaneously normalize. This is a sign of remaining trophoblastic  tissue that must be further investigated.
  • Invasive mola –the molar tissue invades the myometrium and can result in a uterine perforation and intraabdominal bleeding. Metastases can appear in the pelvic region or distant organs.
  • Choriocarcinoma  – can appear in all forms of pregnancies (including birth, abortion, extrauterine pregnancy complete mole or partial mole). It differs from invasive mole by lacking chorionic villi  and growing in a biphasic pattern with syncytio- and cytotrophoblasts. There is often bleeding a large necrosis. This tumor grows rapidly and metastasizes early. 
  • Placenta-site-trophoblasic tumor   – originate from trophoblasts in the placental implantation site. This is a rare tumor with malignant differentiation of mainly cytotrophoblasts, and to some degree also of the syncytiotrophoblasts, and thus demonstrate a lower serum hCG compared to choriocarcinomas. It can be associated with an elevated HPL level.
  • Epithelioid  trophoblastic tumor – supposed to originate from specialized intermediate trophoblastic cells in the implantation site and chorion leave similar to placental site tumor. These tumors are difficult to diagnose and require special pathologic expertise.

Common for the two types of moles is the trophoblastic proliferation producing the increased level of hCG in serum. Moles are considered a premalignant condition. About  2–5 % of the partial and 8–15 % of complete moles develop into persistent trophoblastic disease or choriocarcinoma. 

Staging of gestational trophoblastic disease

Trophoblastic diseases are staged according to FIGO (The International Federation of Gynecology and Obstetrics) and WHO (World Health Organization) risk scores.

Staging according to FIGO

Stage I: The tumor does not extend beyond the uterus.  

/upload/trofoblastsykdom/stadier/trofoblast_stadium1.gif

Stage II: The tumor extends to the adnexa, parametria, or vagina.

 /upload/trofoblastsykdom/stadier/trofoblast_stadium2.gif

Stage III: Lung metastases. Only lung metastases visible on conventional lung X-ray are included in the scoring system. Small metastases visible only on CT are not included, unless there are many of them. 

Stage IV: Metastases to other localization.

WHO risk score
Factors 0 1 2 4
Age < 40
> 40
   
Pregnancy Molar Abortion Full-term  
Interval*  < 4 4-6 7-12 > 12
Serum h-CG (lU/L)** < 103 103-104 104-105 > 105
Largest tumor (cm)***   3-5 > 5  
Metastases localization  Lung****/vaginal Spleen/kidney Intestines Brain/liver
Number of metastases  0 1-4 4-8 > 8
Previous chemotherapy     1 drug Multiple drugs

*   The number of months from last finished pregnancy to start of chemotherapy

** hCG value at the time of initiation of treatment

*** Including tumor in uterus

**** Lung metastases are assessed on chest X-ray, not on CT

***** All metastases should be counted, regardless of localization

Low risk group: <=6

  • Non-metastatic: Stage I
  • Metastatic: > Stage I

High risk group: > 6

Placental-site trophoblastic tumors are a special disease group which are only classified according to FIGO stage.   

Metastatic patterns gestational trophoblastic disease

Trophoblastic diseases metastasize primarily hematogenously. The most common localization is the lungs. Metastasis to the brain, liver, and kidney may occur as well as to the vagina, cervix, and uterus.

Placental-site tumors usually spread via the lymphatic system.

Symptoms gestational trophoblastic disease

  • Vaginal bleeding
  • Excessive uterine size
  • Prominent ovarian theca-lutein cysts
  • Toxemia, preclampsia
  • Hyperemesis
  • Hyperthyroidism (high hCG)
  • Trophoblastic emboli, respiratory distress

Symptoms of distant metastases:

  • Hemoptysis from lung metastasis
  • Neurologic findings from brain metastasis
  • Hematuria

Some cases start with symptoms from metastases in the absence of local symptoms. Trophoblastic disease should always be considered in women of fertile age with multiple lung metastases.

Differential diagnoses of gestational trophoblastic disease

  • Normal pregnancy
  • Ectopic pregnancy

Germinal cell tumors, lung cancer, and brain tumors may produce hCG.   

Prognosis of gestational trophoblastic disease

Patients in the low risk group have a 100% cure rate. Fertility can be spared in the large majority of cases. 

Patients in the high-risk group have 60–80% possibility for cure (2,3).

References on gestational trophoblastic disease

  1. Cancer in Norway 2011, Cancer Registry of Norway, Institute of Population-based Research. Oslo, Norway
  2. Berkowitz RS, Goldstein DP. Gestational Trophoblastic Neoplasia. I: Berek JS, Hacker NF, eds. Practical Gynecologic Oncology. Baltimore : Williams & Wilkins, 1994: 457–78.
  3. Hancock BW, Newlands ES, Berkowitz RS, eds. Gestational trophoblasic disease. London : Chapman & Hall; Medical, 1997: 1–258.
  4. Kohorn EI. Evaluation of the Criteria Used to Make the Diagnoses of Nonmetastatic Gestational Trophoblastic Neoplasia. Gynecol Oncol 1993; 48: 139–47.
  5. Kohorn EI. Clinical Opinion. The Trophoblastic Tower of Babel : Classification Systems of Metastatic Gestational Trophoblastic Neoplasia. Gynecol Oncol 1995; 56: 280–8.
  6. Soper JT, Lewis Jr JL, Hammond C. Gestational trophoblastic disease. I: Hoskins WJ, Perez CA, Toung R (eds.) Principles and Practise of Gynecologic Oncology (2. edition). Philadelphia: Lippincott Williams & Wilkins, 2005, Chapter 36, 1039–77.
  7. Gestational trophoblastic disease. Semin Oncol 1995; 22: 95–171.
  8. Baergen RN, Rutgers JL, Young RH, Osann K, Scully RE: Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 2006;100 (3);511–20.

Diagnostics of gestational trophoblastic disease

Findings

  • Excessive uteri enlargement related to gestational age
  • Bilaterally enlarged ovaries (thecalutein cysts)
  • Ovarian hyperstimulation. This condition may lead to ascites and pleural fluid.
  • Ultrasonography shows a characteristic vesicular pattern, a "snowstorm" pattern.

Examinations

  • Gynecological examination
  • Vaginal ultrasound examination (bladder formation in the uterus)
  • Serum hCG
  • Lung X-ray and CT
  • Abdominal CT or ultrasound abdomen
  • MRI of brain for high risk patients

A biopsy of metastasis-suspect lesions should not be performed due to risk of bleeding.

Trophoblastic disease should always be considered in women of fertile age with multiple lung metastases. Lung biopsies may cause fatal bleeding in these patients. 

Treatment of gestational trophoblastic disease

The choice of treatment depends on the extent of the disease and hCG level (WHO score).

Treatment for mole and choriocarcinoma

  • Uterine evacuation. The uterine cavity is completely evacuated and all material sent for histological examination.
  • Serum hCG is monitored every other week for 8 weeks. With normal serum hCG (<1 IE) after 8 weeks, hCG is monitored monthly for 6 months. For elevated hCG after 8 weeks, s-hCG is monitored every other week to normalization, thereafter monthly follow-up.
  • Re-evacuation should not be carried out.
  • Birth control usually in the form of birth control pills is recommended for 6 months, thereafter the woman may become pregnant again. 

The Norwegian Radium Hospital should be contacted if:

  • increasing hCG levels after evacuation. Control test should be taken after 1 week.
  • serum hCG plateau for more than 4 weeks
  • histological diagnosis of choriocarcinoma or placental-site trophoblastic tumor
  • confirmation of metastasic disease 

Determining factors for choosing chemotherapy (5,6):

  • Course of serum hCG values over time
  • Choriocarcinoma, placental-site tumor and metastatic disease 
  • WHO risk score and FIGO stage

Surgery of gestational trophoblastic disease

In older patients without fertility wishes, a hysterectomy may be considered for localized disease.

Placental-site trophoblastic tumors are treated primarily by hysterectomy since these tumors are relatively chemo-resistent. Metastases from placental-site tumors are treated by surgical extirpation if possible, often in combination with cisplatin-based combination chemotherapy. 

Drug therapy of gestational trophoblastic disease

Drug therapy for trophoblastic tumors is centralized to the Norwegian Radium Hospital. Trophoblastic tumors are very sensitive to chemotherapy and the patient is cured in most cases. Fertility can almost always be preserved.

The choice of therapy depends on the extent of the disease. Low risk patients are treated with low-dose methotrexate. If adequate effect is not achieved, this is changed to dactinomycin, which is usually given for 2 -3 courses after normalization of s-hCG (hCG <1). If resistance to these drugs develops, combination chemotherapy is given. Patients in the low risk group are hospitalized for about 1 week for the first admittance. The treatment duration is about 3 months. 

High risk patients are treated with combination chemotherapy. For extensive lung metastases and metastases to the brain or liver, 1-2 courses of low-dose methotrexate are given before combination treatment, to avoid extensive tumor necrosis. The most common combination treatment is EMA-CO. The treatment continues normally for 6-8 weeks after normalization of  s-hCG (hCG <1). Patients in the high risk group are hospitalized for about 2-3 weeks at the first admittance. The treatment duration may be 4- 6 months, or longer.

 

PROSEDYRER

Dactinomycin

General

 

Indication

  • Gestational trophoblastic disease

The course is given only if:

  • Leukocytes ≥ 3.0 x 109/L
  • Trombocytes ≥ 100,000 x 109/L

If values are too low, the course can be postponed until the lowest acceptable values are reached.

Course duration 

4 days

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EMA-CO

General

 

Indication

  • Gestational trophoblastic disease

Preparation

 

A VAP is always inserted.

Blood tests before each course of chemotherapy

  • Hemoglobin
  • Leukocytes
  • Neutrophiles
  • Thrombocytes
  • S-creatinine
  • S-magnesium
  • S-bilirubin
  • LD
  • ALAT
  • ALP
  • hCG

The drug is given if:

  • Leukocytes ≥ 3,0 x 109/L
  • Granulocytes ≥ 1,5 x 109/L
  • Thrombocytes ≥ 100.000 x 109/L

EKG is taken before starting.

Before the next course of chemotherapy

  • Granulocytes ≥ 1.0 x 109/L V. If values are too low, the course can be given with Neupogen®/Neulasta®.  
  • Thrombocytes ≥ 75,000 x 109/L
Hematopoietic growth factor should be used to avoid postponement of the next chemotherapy course.

Antiemetic treatment

Patients should be given an oral antiemetic as prophylaxis. Navoban® or Zofran® can be given or other antiemetic, or supplemented with a steroid before the course.

Implementation

Interval between courses

2 weeks. New course starts on day 15.

4-6 week treatment after normalized hCG (<5).

Course duration

2 days + day 8  

Day 1

Hydration

NaCl 9 mg/ml 1000 ml with sodium bicarbonate 167 mmol

Infusion time: 1 hour

Antiemetic

5HT3 antagonist (Zofran®, Navoban® or other antiemetic) + dexamethasone. Given as infusion in 100 ml NaCl  9 mg/ml. Given parallel with hydration.       

Etoposide

Mixed with 500 ml NaCl 9 mg/ml

Infusion time: 1 hour

Oxygen and emergency supplies should be available during the infusion. 

Dactinomycin

Mixed with 100 ml NaCl 9 mg/ml

Infusion time: 10 minutes

The patient must be monitored during the entire infusion for extravasation. Using an infusion pump is not allowed due to the danger of extravasation. 

Methotrexate  

Mixed with 1000 ml NaCl 9 mg/ml with sodium hydrogen carbonate based on the weight of the patient.

Infusion time: 12 hours

  • Calcium folinate (leucovorin) 15 mg tablet, is given every 6 hours from 24 hours after starting MTX until serum MTX is < 50 mmol/l. The first serum measurement should be 24 hours after starting MTX.
  • Sodium hydrogen carbonate 1g is given every 6 hours after starting MTX and is given until serum MTX < 50 mmol/l. The first serum measurement should be 24 hours after starting MTX.
  • Urine pH is measured before starting MTX and thereafter every 4 hours until serum MTX < 50. For pH < 7, 3 g of sodium hydrogen carbonate is given in tablet form or 1000 sodium hydrogen carbonate 167 mmol/l intravenously (over 1 hour).
  • Diuresis is monitored from start of prehydration. Diuresis should be > 400 ml/4 hours around the clock. If diuresis < 400 ml/4 hours, Lasix 10-20 mg is given intravenously. 

Day 2

Hydration

1000 ml NaCl 9 mg/ml

Infusion time: 90 minutes

Given parallel with chemotherapy drugs. 

Antiemetic

5HT3 antagonist (Zofran®, Navoban® or other antiemetic) + dexamethasone. Given as infusion in 100 ml NaCl 9 mg/ml. Given simultaneously with hydration.

Etoposide

Mixed in 500 ml NaCl 9 mg/ml

Infusion time: 1 hour

Etoposide is given together with hydration.

Oxygen and emergency supplies should be available during the infusion. 

Dactinomycin

Mixed in 100 ml NaCl 9 mg/ml

Infusion time: 10 minutes

The patient must be monitored during the entire infusion for extravasation. Use of an infusion pump is not allowed due to the danger of extravasation.

Day 8 

This course is often given at the local hospital.

Hydration

500 ml NaCl 9 mg/ml

Infusion time: 1 hour

Given simultaneously with chemotherapy drugs.

Antiemetic

5HT3 antagonist (Zofran®, Navoban® or other antiemetic) + dexamethasone.  Given as infusion in 100 ml NaCl 9 mg/ml simultaneously with hydration.

Vincristine

Infused directly into the hydration drip. Use caution. Extremely tissue toxic.

Infusion time: 3 minutes

Cyclophosphamide

Mixed into 250 ml NaCl 9 mg/ml

Infusion time: 30 minutes

 

Follow-up

Side effects

  • Treatment with methotrexate, etoposide, and cyclophosphamide may cause bone marrow changes. 
  • Patients should be informed of the risk of febrile neutropenia during the interval between infusions, and that it is necessary to contact a doctor with a fever over 38°C.
  • Neuropathy. Vincristine may affect peripheral nerves and cause peripheral neuropathy.
  • CNS. Methotrexate may cause meningeal irritation with temporary or permanent paresthesia/encephalopathy. However, this is very rare at this dosage.
  • Kidney changes. Methotrexate may cause tubular necrosis. Good hydration with calcium folinate and sodium bicarbonate is important.
  • Liver changes. Long-term use of methotrexate may cause liver damage. Methotrexate is eliminated via the liver and therefore increases toxicity by reduced liver function. If the liver is affected and s-bilirubin > 2 x the upper normal limit, methotrexate should be stopped due to the increased risk for toxicity.
  • Lung changes. Methotrexate may cause pneumonitis.

Hypersensitivity reactions

Etoposide may cause allergic reactions. Symptoms of allergic reactions may be a feeling of warmth in the face, rash and itching, low blood pressure, labored breathing or pressure in the chest, and acute back pain. In rare cases, shock may occur. Fever may also occur.  

Emergency kit and oxygen should be available when etoposide is given.

Weight gain

A large amount of fluid is given with this regimen of chemotherapy. The patient is weighed daily to check for fluid retention. 

Change in bladder mucosa

Cyclophosphamide may change the mucosa of the bladder and cause blood in urine. To prevent this, fluid is given and possibly Mesna. 

Tissue irritation

Vincristine and dactinomycin are extremely tissue toxic. If there is suspicion of extravasation, the infusion must be stopped immediately and a surgeon contacted. Additional fluid should not be injected through the venflon, which should not be removed. 

The side drip should be given concomitant with dactinomycin and vincristine to reduce the risk of vein contraction.

Mucositis/Stomatitis

Mucositis/stomatitis may be prevented by adequate mouth and dental hygiene. Use mouth rinse such as saline water, leucovorin, or Düsseldorf rinse.

Sore eyes

Rinse with 15 mg leucovorin in 30 ml saline water.  

Hair loss

Moderate to total hair loss can be expected with this regimen.

EMA-EP

General

 

Indication

  • Gestational trophoblastic disease

Course is given day 1 and day 2 if:

  • Leukocytes ≥ 3.0 x 109/L
  • Neutrophile ≥ 1.5 x 109/L
  • Thrombocytes ≥ 100,000 x 109/L

Cycle starts again on day 8 if: 

  • Leukocytes ≥ 2.0 x 109/L
  • Neutrophile ≥ 1.0 x 109/L
  • Thrombocytes ≥ 75.000 x 109/L

If values are too low, the regimen is postponed until minimum values are reached.

Course duration 

2 days + day 8

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Methotrexate (low-dose)

General

 

Indication

  • Gestational trophoblastic disease

Preparation

 

Blood tests before each course

  • Hemoglobin
  • Leukocytes
  • Neutrophiles
  • Thrombocytes
  • S-creatinine
  • S-bilirubin
  • hCG

The course is given if:

  • Leukocytes ≥ 3.0 x 109/L
  • Neutrophiles ≥ 1.5 x 109/L
  • Thrombocytes ≥ 100,000 x 109/L  

Before next course

Before the next course is given, the granulocyte value should be 1.5 x 109/L, but the course can be given with lower values if Neupogen®/Neulasta® is given. 

The thrombocyte value should be 100,000 x 109/L.

Implementation

Course duration

4 days

Interval between courses

New course starts day 12

Number of courses

2 courses after hCG < 5 (lowest measurable limit)

Dosage

Methotrexate 25 mg injected intramuscularly

Special requirements

hCG should be taken on day 1.

Leucovorin (calcium folinate)

15 mg leucovorin (calcium folinate) is given orally 8 and 14 hours after the last methotrexate injection. If the patient is not able to take a tablet, the same dose can be given intravenously or intramuscularly.

 

Follow-up

Side effects|

Methotrexate can be toxic to the liver and kidneys.

Bone marrow toxicity is low. It is important to maintain intervals between courses.

Mucositis is a frequent side effect. Good oral hygiene is therefore important. Mouth wash (leucovorin/düsseldorf mixture), possibly a Decadron 4 mg tablet in 30 ml NaCl 9 mg/ml for mouth rinsing, or possibly antifungal treatment.

Moderate alopecia is normal.

Sun Exposure under Drug Therapy

General

Correct information about the possibility of sunbathing may affect patients health and quality of life.

Precautions in connection with sunbathing should be followed under medical cancer treatment and for 2-3 weeks after end of treatment.

Drug cancer treatment includes chemotherapy, antibodies and other drugs used in cancer treatment.

Indication

Sun exposure in connection with drug cancer treatment.

Goal

Prevent sun damage of the skin during and after cancer drug treatment.

Definitions

Photosensitivity

Increased sensitivity to ultraviolet light have been associated with certain drugs used in cancer treatment. Photosensitivity reactions can be expressed in various ways. They can be phototoxic, which is by far the most common, or photoallergic (8,14). Druginduced photosensitivity is mainly caused by wavelengths in the UVA range, but UVB rays may also be involved (8).

Phototoxicity

A phototoxic reaction is reminiscent of a reinforced sunburn, with redness, edema, pain and increased sensitivity in sun-exposed areas of the skin. This is caused by a photochemical reaction of a photosensitive drug and irradiation of sunlight on the skin, which leads to skin cell death. In severe cases, blistering can occur (14). Symptoms may appear immediately or as a delayed inflammatory reaction (3). Higher doses of medication will give an increased risk of skin reaction (14). Healing of skin area will often lead to a hyperpigmentation that can last from weeks to months before they might disappear (8). Although the incidence of drug-induced photosensitivity is unknown, phototoxic reactions is possibly more common than is diagnosed or reported.

Photoallergy

An immunological reaction usually occurring 24-72 hours after sun exposure. The reaction degenerates as an itchy, eczema-like eruptions. In acute cases, one can see rash liquids. The prevalence of eczema is usually limited to sun-exposed skin, but can in severe cases spread to larger areas of the body. Unlike a phototoxic reaction, photoallergy is less dependent on the dose of the causative drug (8).

Photoinstability

Some drugs can be degraded when exposed to light. This can happen both before administration and when the drug is circulating in the body. This degradation can cause redness/rash and edema of the skin. This applies especially for dacarbazine (9). It is unknown whether the effect of the drug is affected and it is therefore recommended that one avoids direct sunlight as long as the drug is active in the body.

PPE ( palmoplantar erythrodysesthesia = Acral erythema )

PPE is also called hand-foot syndrom. The condition starts with altered skin sensation that develops into burning pain, swelling and redness of palm of the hands and soles of the feet. The symptoms can also occur in other parts of the body that is subjected to pressure, for example under tight clothing. In severe cases large blisters and ulceration can develop. The pain can be so severe that daily activities is limited.

PPE is often seen with liposomal doxorubicin (Caelyx®) and high dose cytarabine, but may in principle occur with any anthracyclines, taxanes and fluorouracil (5- FU® ) (9,14) .

Acne-like rash

Pimple-like eruptions in skin areas with a lot of sebaceous glands such as the face, scalp, chest and neck. In contrast to common acne, the liquid-filled blisters does not contain any bacteria (9,10,15).

Hyperpigmentation

Hyperpigmentation is a common side effect in patients receiving chemotherapy, especially alkylating drugs and antibiotics with cytostatic effect. The area that has increased pigmentation may be localized or diffusely distributed. It can occur in the skin, mucous membranes, hair and nails. Pigment changes can be normalized upon discontinuation of the drug, but it may also persist.

Fluorouracil is one of the most common drugs which can provide hyperpigmentation. Others are; metotrexate, busulfan, doxorubicin liposomal, Hydroksyurea®, procarbazine, bleomycin, cyclophosphamide, doxorubicin , ifosfamide, tegafur, mitoxantrone, daunorubicin, fluorouracil, cisplatin, carmustine, thiotepa, docetaxel, vinorelbine, vincristine, imatinib and combination regimens (14).

An increased pigmentation in sun-exposed areas with the use of methotrexate, fluorouracil and capecitabine is described (16,17,18). Beyond that there is little evidence in the literature  that hyperpigmentation aggravates by sun exposure.

Radiation Recall Dermatitis (RRD)/Photo Toxic recall reaction

Flares of an inflammatory skin reaction in an area of ​​previous radiation damaged skin resulting from sunburn or external radiation. RRD can occur from months to years after the initial radiation damage.

Drugs that can provide RRD are; bleomycin, capecitabine, cyclophosphamide, dactinomycin, cytarabine, daunorubicin, docetaxel, doxorubicin liposomal, doxorubicin, etoposide, fluorouracil, gemcitabine, Hydroksyurea® , idarubicin, lomustine, melphalan, methotrexate, paclitaxel, tamoxifen and vinblastine (14). EGFR inhibitors (cetuximab , gefitinib and erlotinib) may also cause other skin reactions that may be exacerbated by sun exposure (9,10,19).

Preparation

The patient is given written and verbal information by the medical responsible doctor and nurse at the start of the drug cancer treatment, and it is repeated as necessary.

Implementation

General Precautions

Prevention and protection:
  • Limit sun exposure during the first days after the cure.
  • Observe skin daily to detect any skin reactions early.
  • Avoid getting sunburned.
  • View extra care between 12.00-15.00 (2).
  • Wear protective clothing and headgear (2,3,4,5,6).
  • Wide-brimmed hats protect better than caps (2.4).
  • Please note that the window glass does not protect against UVA rays (7).
  • Use sunscreen; to protect against UVA and UVB rays, a minimum SPF 15 (3,4,6,8) is applied several times daily.
  • Use mild skin care products without perfumes.

In case of an eruption, sun exposure (including solarium) should be avoided until the skin is healed. Adverse skin reactions can be alleviated with moist and cooling compresses. Mild cortisone salves can also be highly effective. For very severe cases, systemic cortisone might be necessary (3,6,7,9).

When a photosensitive reaction occurs, it is important to consider what other medications the patient is receiving which can also trigger such reactions. For example, steroids, some antibiotics, diuretics and NSAIDs.

Medicaments that most commonly cause skin reactions

Medicament Common reactions Remedial action
Dakarbazin (DTIC)


Phototoxic/photoinstability
See general precautions
Redness in skin, tingling of the scalp and general unwellness
Avoid sunlight completely the day of the treatment (9)
Methotrexate
Phototoxic

See general precautions
Acne-like rash
Avoid direct sun exposure, heat and humidity (9,10). Avoid soap, alcohol based skin products (9). Use moisturizing products and oil bath (4,9,10).
Palmoplantar erythrodysesthesia = Acral erythema (PPE)

Preventive: Pyridoxin (vitamine B6) (2,6,9)

Avoid sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths

(2, 9)

Fluorouracil (5-FU®)

 

Phototoxic See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2,6,9)

Avoid sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths   (2, 9)

Radiation recall
Treatment as with phototoxic

Kapecitabin (Xeloda®)

 

Phototoxic See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE)

Preventive: Pyridoxin (vitamin B6) (2, 6, 9). Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths (2, 9)

Vinblastin

 

Phototoxic
See general precautions
Radiation recall Treatment as with phototoxic
Doxorubicin liposomal (Caelyx®)
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths (2, 9)

Tegafur

 

Phototoxic
See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths    (2, 9)

EGFR-hemmere

(Cetuximab, panitumab, erlotinib, gefitinib, lapatinib, vandetanib)

Phototoxic
See general precautions
Acne-like rash
Avoid direct sun exposure, heat and humidity (9,10). Avoid soap, alcohol based skin products (9). Use moisturizing products and oil bath(4, 9, 10).

Beyond the medications listed in the table the literature gives som evidence that these substances may cause phototoxic skin reactions :

  • paclitaxel (Taxol®)
  • docetaxel (Taxotere®)
  • hydroxycarbamide ( Hydroksyurea® )
  • imatinib ( Glivec® ) and Dapson® and that paclitaxel can provide radiation recall .

References


  1. LOV-1999-07-02-63 Pasientrettighetsloven - pasrl. Lov om pasientrettigheter.
  2. Polovich M, White JM, Kelleher LO. Chemotherapy and biotherapy guidelines: recommendations for practice. Pittsburgh, PA: Oncology Nursing Society; 2005.
  3. González E, González S. Drug photosensitivity, idiopathic photodermatoses,and sunscreens. J Am Acad Dermatol 1996;35:871-85;quiz 886-7.
  4. Liffrig, JR. Phototrauma prevention. Wilderness Environ Med 2001;12:195-200.
  5. Tan E. Skin toxicity of chemotherapy drugs [created 2007, last updated  2010 Mar 5]. Hentet 1. desember 2010 fra: http://dermnetnz.org/reactions/chemotherapy-toxicity.html
  6. Gould JW, Mercurio MG, Elmets CA. Cutaneous photosensitivity diseases induced by exogenous agents. J Am Acad Dermatol 1995;33:551-73.
  7. Payne, AS & Bernandin, RM. Sunburn [topic last updated 2010 Oct 06]. I: BMJ Best Practice. Hentet 23. november 2010 fra http://bestpractice.bmj.com
  8. Zhang AY, Elmets CA. Drug-induced photosensitivity [updated 2010 Jan 15]. Hentet 1. desember 2010 fra: http://emedicine.medscape.com/article/1049648-overview
  9. Ulrich J, Hartmann JT, Dörr W, Ugurel S. Skin toxicity of anti-cancer therapy. J Dtsch Dermatol Ges 2008;6:959-77.
  10. Agero AL, Dusza SW, Benvenuto-Andrade C, Busam KJ, Myskowski P, Halpern AC.Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol 2006;55:657-70
  11. Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol 2002;14:212-6.
  12. Mangili G, Petrone M, Gentile C, De Marzi P, Viganò R, Rabaiotti E. Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling. Gynecol Oncol 2008;108:332-5.
  13. Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK. Predisposingrisk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. Gynecol Oncol 2009;114:219-24.
  14. Payne AS, Savarese DMF. Cutaneous complications of conventional chemotherapy agents. I: UpToDate [version 18.2 2010]. Hentet 1. desember 2010 fra: http://www.uptodate.com
  15. Heidary N, Naik H, Burgin S. Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol 2008;58:545-70.
  16. RELIS Sør. Hyperpigmentering av cytostatika og forverring av sollys. I: RELIS database 2010, Spm.nr 4736. Hentet 1. desember fra: http://relis.arnett.no/Utredning_Ekstern.aspx?Relis=2&S=4736
  17. Hendrix JD Jr, Greer KE. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol 1992;31:458-66.
  18. Schmid-Wendtner MH, Wendtner CM, Volkenandt M, Heinemann V. Clinical picture: leopard-like vitiligo with capecitabine. Lancet 2001;358(9293):1575.
  19. Segaert S, Tabernero J, Chosidow O, Dirschka T, Elsner J, Mancini L, et al. The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges 2005;3:599-606.

Preparation of Chemotherapy, Spills, and Cleaning a LAF Bench

General

Preparation of chemotherapy outside of a pharmacy

At Oslo University Hospital, the pharmacy primarily prepares chemotherapy for each patient. If it is necessary to dilute/mix the medicine at the department, then this should occur in a designated room with a LAF bench (laminar airflow bench). Many chemotherapy drugs are carcinogenic and teratogenic, and it is extremely important for health personnel to follow directions for preparation of of these medications. At Oslo University Hospital, all chemotherapy should be prepared and administered by a nurse who has completed a cytostatic treatment course at Oslo University Hospital, or by nurses who are certified cancer nurses from Oslo University College.

Pregnant women and employees under physician orders not to temporarily or permanently work with chemotherapy drugs, should not handle or be exposed to these chemicals. Nursing mothers may handle chemotherapy drugs as long as they follow the general guidelines for chemotherapy handling. For each work place, there should be written guidelines for handling of chemotherapy drugs and for first aid for spills and maintenance of fume hoods etc..

Designated room with LAF-bench to dilute/mix chemotherapy

  • The ventilation should be separate from the main ventilation and fumes should be vented to the outside and if necessary, filtered.
  • The room should be well illuminated for visual control of the fluid.
  • The LAF bench should be a workbench having sterile, filtered air from the ceiling with defined speed and an approved fume hood. The bench should be routinely tested and approved.

Goal

  • To protect nurses and surroundings from exposure to cytotoxic chemicals and to preserve the sterility of the drug.

Handling of chemotherapy spills

Chemotherapy drugs are a heterogeneous group of drugs in which many are known mutagens, teratogens and/or carcinogens. Allergic reactions have also been reported. Studies show that there is a health risk during exposure of chemotherapy drugs and there are guidelines for minimizing exposure of health personnel to these chemicals. Workers in daily contact with these drugs will be more at risk due to the increasing use of chemotherapy. Chemotherapy spills refers to spills during preparation and leakage from infusion bags.

Goal

  • To ensure that spills of chemotherapy drugs or waste materials that contain these chemicals are handled in a safe way to protect health and safety.

Cleaning of LAF-bench

The Norwegian Work Authority recommends that each workplace should have written guidelines for handling chemotherapy drugs, first aid for spills, and maintenance of fume hoods etc. A LAF-bench (laminar airflow bench) is a bench protecting workers from the drug being prepared and also protects from microbiological organisms. Those who carry out cleaning should have training and knowledge of the risk for exposure to chemotherapy drugs.

Goal

  • Maintain a clean LAF bench
  • Avoid contamination and preserve the sterility of the drug 
  • Protect people and surroundings from exposure

Source

Applicable directives and guidelines (www.lovdata.no)

  • Warn against exposure to chemicals at the workplace (Kjemikalieforskriften §24), mandated by The Norwegian Labour Inspection Agency from 5 May 2001, last edition from 26 April 2005.
  • Guidance for chemical directives attachment VII Cytostatica from September 2003 (www.arbeidstilsynet.no).

Equipment

  Preparation of chemotherapy in a hospital

  • 2 pairs of gloves: vinyl gloves inside and sterile, powder-free latex gloves outside
  • Protective coat with long arms/plastic apron
  • Arm protectors
  • LAF bench
  • Dilution fluid
  • Syringes and cannulas
  • Sterile compresses
  • Disposable cloths
  • 70% ethanol
  • Absorbent benchcoat with plastic underside for the work bench
  • If a LAF bench is not used, use a protective mask with aerosol filter and protective goggles.

Handling of chemotherapy spills

Spill kit includes:

  • 2 pairs of nitrile gloves, long
  • 2 pairs of latex gloves, long
  • 2 pairs of shoe covers
  • Plastic coat\apron
  • 1 mask
  • 2 diapers
  • 1 bed absorbent bed sheet
  • 2 plastic bags with zippers (30 x 40 cm)
  • 4 thin, white plastic bags (60 x 90 cm)
  • Absorbant material   
  • 8 disposable wash cloths

Washing of LAF-bench

  • Plastic apron
  • Arm protectors
  • Gloves: either double vinyl gloves or special gloves
  • Disposable cloths
  • 70% ethanol
  • Bucket and soapy water
  • Waste container with plastic bag for chemotherapy waste (biohazardous waste)

 

 

Preparation

Preparation of chemotherapy outside of the pharmacy

For preparation of chemotherapy drugs, use gloves and a protective lab coat with long arms or tight-fitting cuffs.   Use two pairs of gloves where the inner pair is vinyl or other latex-free material. The outer glove should be sterile and of latex or other material which is impenetrable.  The gloves are recommended to be changed every half hour for preparation of chemotherapy drugs, and right away with spills.

  • Start the LAF-bench a minimum of 30 minutes before use.
  • Wash hands
  • Put on the inner gloves
  • Disinfect the work surface with 70% ethanol
  • Cover the work surface with a benchcoat. This should not cover the vent; otherwise, the bench will not function properly.
  • Read the dilution directions and find the necessary equipment and medications as described.
  • Choice of dilution system/fluids
    • A transfer cannula should be used in preference to a syringe where possible to maintain a closed system as much as possible.
    • If a syringe is used: use a syringe with Luer lock connection. These have a better connection between the syringe and the cannula.
  • Check the expiration on the drug packaging and infusion fluid.
  • Check that the drug in liquid form does not contain particles or visible solids.
  • Check that the packaging does not have any cracks or leakages.
  • Perform necessary calculations, date, and sign the work form.
  • Obtain another nurse to double check: right patient, work form, drug, dosage, fluid type and volume, as well as calculations.  All checks should be against the original ordination. The person doing the check should sign and date it.
  • Set out necessary equipment on the LAF-bench or where the work will take place. The equipment should be placed in the corner within the ventilation of the LAF-bench.  Remove the outer packaging of the sterile gloves and lay the gloves on the bench.
  • Put on the protective clothing (coat/apron and arm protectors)
  • Put on the sterile gloves in the bench
  • Disinfect the rubber membrane on the infusion bag and hood windows as well as the ampules.
  • Make sure the protective glass on the LAF-bench is pulled down to the correct work level as recommended by the manufacturer of the bench.

Handling of chemotherapy spills

All, except the workers who clean the spill, should leave the room.  Preferably, two people should help each other to remove the spill.  This way, one can ensure that proper precautions are taken.

At Oslo University Hospital, a packet is available from the pharmacy for chemotherapy spills.

Washing of LAF-bench

  • The LAF-bench should be operating under cleaning.
  • The sash should be down, as under normal working conditions.
  • Use a plastic apron, arm protectors, and gloves.

 

 

Implementation

Preparation of chemotherapy drugs outside of a pharmacy

Aseptic procedure

  •   To avoid turbulence of the sterile, laminar air stream:
    • Work at least 15 cm inside the perforation with steady movements
    • Avoid hands or other objects from coming between the airflow and the medicine.
  • Make only one medicine at a time.
  • A full syringe or finished bag should be labeled for the next preparation.  The label should be labeled with the patients name, birthdate, drug and dosage, preparation date, expiration, and the name of the person who prepared and checked the medicine.
  • Avoid spills and aerosol formation
    • Use a dry, sterile compress around neck of the ampule when it is broken.
    • When the cannula is removed from the syringe, hold a sterile compress around the barrel neck to catch any spills.
    • Hold the syringe/ampule such that the opening is directed away from the face.
    • For solid substances, solvent should be added along the glass wall to avoid whirling of particles.
    • With positive/negative pressure in the hood glass: apply a filter cannula first to reduce pressure.
    • With use of adapter: place adapter first in the infusion bag and connect to the hood glass with medicine.
    • When the air is removed from the syringe, place the cannula cap on the cannula again while the syringe is held vertically with the cannula upright. A sterile compress should be held around the opening between the cannula and the syringe to collect spillage.
    • Clean up spills at once
  • After each addition, the contents of the infusion container should be mixed well by inverting and repeating 5-6 times.
  • Infusion fluid which has been added to should be marked satisfactorily.
  • The finished solution should be scrutinized for solid or foreign particles. All solid should be dissolved.
  • If visible changes occur under the mixing procedure, the physician should be contacted and the fluid should not be used. Store the infusion fluid and packaging of the added drug and contact the pharmacy (chemist) for further clarification.
  • All used equipment should be rolled up in the benchcoat (alternatively, all used equipment can be placed in a plastic bag which can be tied or closed with zipper) and disposed of in box with plastic bag for chemotherapy waste/biohazardous waste.
  • LAF-bench should be stopped at least 30 minutes after use.

Multiple additions

  • Addition of multiple drugs for chemotherapy solutions should be avoided. If it is still appropriate, there should be clear documentation of the mixture.
  • Different chemotherapies can mix if their mixing properties are documented (and checked with pharmacist).

Handling of chemotherapy spills

  • Use two pairs of disposable latex\nitrile gloves, plastic coat, mask, shoe covers (used with floor spills) and protective goggles.
  • Lay the smallest diaper in the middle of the spilled fluid. Then, place the absorbent bed sheet over the diaper and the rest of the fluid. Use more diapers and absorbent material if necessary.
  • Dispose of used diapers, absorbent material, bed sheets, and gloves is appropriate waste container, which can be closed.
  • Use new gloves and wash thereafter with soapy water and disposable wash cloths a minimum of three times. Use a new cloth before each wash. Used cloths should not be put back in the wash solution.  Used cloths and gloves should be disposed in the appropriate waste containers (in plastic bags which can be closed).
  • The plastic bags with used equipment should be disposed of in the appropriate containers which are properly labeled.

Washing of LAF-bench

  • Other than a cannula bucket, nothing should be stored in the bench after the last preparation.
  • Washing with 70% ethanol is sufficient if there are no visible spills.
  • For visible spills, wash the bench with soapy water and spray afterwards with 70% ethanol (see procedure under). Soapy water is the most effective for removing chemotherapy spills.

Routine washing

  • Washing should be done every 1-4 weeks depending on frequency of use.
  • Spills and dust pose risks for washing.
  • It is important that any remaining solution of chemotherapy is not spread under washing.
  • Use disposable cloths.
  • To avoid contamination of washing water, the washing hand should not be dipped in the water.
  • Wash with slow movements and use a new cloth as needed.
  • Cloths that have been in contact with the bench should not be put back in the washing water and should be discarded in proper waste container.
  • Wash first the walls from top to bottom with soapy water (the cleanest to the most contaminated) – place the cloth on a squeegee for hard-to-reach areas.
  • The filter in the ceiling of the bench should not be washed.
  • Wash the work surface in the bench – wash from back to forward (from the cleanest to the most contaminated).
  • Raise the work surface.
  • Wash the work surface on the underside, especially the closest, perforated part.
  • Then wash the underside bottom of the work surface.
  • Wash thereafter all surfaces (not the ceiling) with 70% ethanol.
  • Remove protective clothing.
  • Discard all protective clothing for one-time use and washcloths in the appropriate waste container.
  • Wash hands.
  • Replace the cannula bucket.
  • There should be a record for bench washing; the employee who washes should sign and date the record.

Follow-up

Aerosol formation with spraying or squirting can occur:
  • when a syringe is used and cannula is retracted for transfer
  • when an ampule is broken
  • when air is removed to measure volume
  • with a leak in a syringe or IV catheter
  • with waste handling

First aid if contact with chemotherapy drugs

  • Skin: Rinse well with water for 15 minutes. Wash contacted area with regular soap.
  • Eyes: Rinse well with water, or use spray bottle with NaCl 9 mg/ml (at least 20-30 minutes of continual rinsing).
  • Contact a doctor.

Radiation therapy of gestational trophoblastic disease

Radiation therapy is not routinely given for gestational trophoblastic disease.

Complication treatment of gestational trophoblastic disease

Surgery, chemotherapy, and radiation therapy cause side effects to varying degrees.

It is usually necessary to provide supportive care in order for the patient to complete the planned treatment and obtain its full effect.

Supportive care can also be provided to reduce side effects and improve the patient's quality of life during and after treatment.

PROSEDYRER

Nutrition during Cancer Treatment

General

Monitoring the patient's nutritional status is an important part of cancer treatment. The goal is to identify malnutrition as early as possible in order to initiate treatment as quickly as possible.

Measures include diet according to symptoms and the nutritional condition. The patient should be offered nutrition-rich food, snacks, nutritional drinks, tube feeding and intravenous nutrition.

Because cancer treatment breaks down both cancer cells and normal cells, the body requires an adequate supply of nourishment to increase growth of new cells. 

In cancer patients, the sensation of hunger is not always present to the necessary degree. In these cases, it is important to take actions to improve the nutritional status of the patient. The nutritional condition is easiest followed by monitoring body weight over time.

Indication

  • Cancer treatment (chemotherapy, radiation, surgery).

Goal

  • Maintain nutritional status in order for the patient to have the best possible conditions for implementing treatment.

Definitions

Subjective Global Assessment (SGA)

Subjective Global Assessment (SGA) is a scheme for classifying the patient's nutritional status.

Other tables that are frequently used are Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA) and Nutrition Risk Score (NRS). In principle, these schemes are prepared in the same way as SGA, but they are not validated for patients with cancer.

Weight loss is one of the most important signs of change in nutritional status. A weight loss of more than 15% over the past 6 months or more than 5% over the last month is a significant and serious weight loss. If the weight loss occurs in combination with low BMI (body mass index) (< 20 kg/m2 for adults) and/or a food intake of less than 60% of the calculated requirement over the past 10 days, the patient will be malnourished or be at nutritional risk.

Calculation of nutrition and fluid requirements

  • Ambulatory patients:  30-35 kcal/kg/day
  • Bed-ridden patients:  25-30 kcal/kg/day
  • Elderly above 70 years:  Recommended amount is reduced by 10%
  • Fluid requirement:  30-35 ml/kg/day

Nutritionally enriched diet / enrichment of food and beverages

Nutritional beverages may be used as a meal in itself or between meals. Nutritional drinks can be a more valuable snack than "normal" food, because it is often easier for the patient to drink than to eat. It has been shown that if nutritional drinks are introduced as snacks, it does not affect the energy intake during the main meals.

There are a number of ready-made nutritional drinks on the market. Some of the products are of nutritionally complete. They contain carbohydrates, protein and fat and are supplemented with all the necessary vitamins, minerals and trace minerals and possibly fiber. Some of these products can be used as the sole source of nutrition. The energy content varies from 85-200 kcal/100 ml and some products have a high protein content. Other nutritional drinks are supplement drinks adjusted to individual needs such as allergies, intolerance and special conditions associated with illnesses.

The products are also adapted to age, and the dose is determined individually by a clinical dietician/doctor.

Many patients prefer homemade nutritional drinks based on full fat milk, cream, ice cream, fruit and possibly flavor supplements. These are free of additives and have a fresher taste. The energy and protein content is close to the commercial products and at the same time they are more sensibly priced.

Tube feeding

Tube feeding is preferable to total parenteral nutrition (TPN) when the digestive system is working. Nutrition supply to the intestine is more physiological. It protects against bacterial growth, maintains the intestine's mucous membrane structure and function, and promotes motility. Tube feeding involves less risk of metabolic complications.

Tube feeding is used in the event of

  • insufficient food intake (less than 60% of energy requirements) over the past 5-7 days despite oral intake
  • weight loss >2 % over the past week, >5 % over the past month or >10% over the past 6 months
  • danger of weight loss due to planned treatment
  • low albumin values (under 35 g/l, lower limit for normal area)
  • stenosis with feeding obstacles in pharynx/gullet

Tube feeding must not be used for the following conditions.

  • Paralysis or ileus of the alimentary tract
  • Short bowel syndrome
  • Serious diarrhea
  • Serious acute pancreatitis
  • Obstruction of the intestine
  • Serious fluid problems

Tube feeding solutions

The tube feeding solution must be nutritionally complete because they shall be used as the sole source of nourishment. The most frequently used are standard (1 kcal/ml), fiber-containing (1 kcal/ml) or energy-rich (1.5 kcal/ml). There are also tube feeding solutions which are adapted to patients with digestion and absorption problems, patients with diabetes or lactose allergy, and intensive care patients.

Tube feeding solutions, which are adapted to cancer patients are energy-rich (1.5 kcal/ml). They contain extra omega-3 fatty acids, rich in MCT acid and enriched with extra vitamins and minerals. Recommended dosage is 500 ml/day.

Parenteral nutrition

Parenteral nutrition should only be used if food by mouth or tube feeding cannot be maintained. Parenteral nutrition can also be used as a supplement to tube feeding or ordinary food. 

Precautions must be taken for kidney failure, heart failure, lung failure, large fluid and electrolyte loss, diabetes mellitus and liver failure.

Preparation

The patient is classified as well-nourished, somewhat malnourished or seriously malnourished on the basis of information about weight development, food intake, symptoms and physical functioning. This classification has been shown to correlate well with more objective measurements of nutritional status and morbidity, mortality and quality of life.

Actions include individual adjustment of diet according to symptoms and nutritional status.

Tube feeding

The end of the tube is often inserted into the stomach. In the event of poor gastric function, total gastrectomy or pancreatic resection, the feeding tube should be inserted in the duodenum or jejunum. The position of the feeding tube is vital for the choice of feeding-tube solution and mode of administration.

The most common solution is to insert the tube nasogastrically, but it can also be done through the abdominal wall (PEG).

Parenteral nutrition

It is preferable to use intravenous or parenteral nutrition as a supplement to oral/tube feeding instead of only TPN (total parenteral nutrition).

  • Central veins must be used for TPN with high osmolality.
  • Peripheral veins can be used for short-term parenteral nutrition. In this case, a large vein on the forearm is used and a small needle. Nutrition is then given as more diluted solutions.

Implementation

All patients are weighed regularly (1–2 times each week). This is a prerequisite to being able to register changes in the nutritional status.

Varied and healthy food contributes to the growth of new cells and enhances the immune system.

  • Fruit, berries and vegetables are rich in vitamins, minerals, antioxidants and fiber, which contribute to enhances the immune system and contributes to keeping the digestive system working.
  • Fish, shellfish, poultry, meat, eggs, cheese, milk, beans and nuts are rich in proteins, which are the building blocks of new cells.
  • Bread, rice, pasta, porridge and breakfast cereals supplement the diet with proteins, carbohydrates, fiber, vitamins and minerals.
  • Oil, margarine, butter, mayonnaise products, nuts, cream, heavy cream, desserts etc. are fat and energy rich products, which are important to maintain the energy intake at a satisfactory level.
  • Cancer patients also have a requirement for plenty of fluid, especially during treatment, to discharge waste.

Often, the patients must have an individually adjusted diet. In the event of lack of appetite, it is generally more important that you eat (enough food) than what you eat (the right food). It is beneficial to have small portions and for the food to be as abundant in energy as possible. These patients will often have a need for 6–8 small meals everyday to obtain their energy requirements.

Enrichment of food and drink is done in order to increase the energy content of the food product without increasing the volume. Full-fat products such as full-fat milk, cream, butter, heavy cream, mayonnaise, sugar, honey, eggs and cheese etc. are primarily used. Enrichment powders from pharmacies may also be used. Some powders are nutritionally complete, i.e. they contain everything the body requires in terms of energy and nutrients, while others only contain pure energy (carbohydrates, fat and/or protein). 

Tube feeding

Tube feeding is given continuously with a low drop rate or by interval/bolus administration (individually adapted meals with high drop rate).

When the patient's energy and fluid requirements are fulfilled, it will be decided whether the patient will be given bolus or continuous supply at night, in order to increase mobilization during the day. However, this requires that the patient does not have diarrhea, nausea or other complaints associated with the supply of nutrition.

For a running feeding tube:

  • Every 4-8 hours, it should be aspirated in order to monitor the gastric emptying. This applies especially to immobile and weak patients.
  • Weekly or more often, the nutrition program/fluid balance, evaluation, edema control, blood tests (albumin, K, Mg, P, blood glucose) should be monitored weekly or more often.
  • Every 4-6 weeks, the tube should be changed. Alternate the uses of nostrils avoid irritation in the nose through prolonged feeding.

Experience shows that the use of infusion pumps causes fewer side effects and ensures correct volume and rate.

Bolus supply

Initiation of tube feeding with bolus supply is only recommended

  • if the patient been taking any food until the last 24 hours
  • if the patient is taking some food and requires tube feeding for additional nourishment

It is recommended to use pumps for bolus supply for the first 1–2 days.

Continuous supply

If the patient cannot tolerate bolus supply (vomiting, abdominal discomfort, nausea, diarrhea), reverting to continuous supply should be considered.

Tube feeding should always be administered continuously to very malnourished patients or if the tube end is located distally to the pylorus.

Parenteral nutrition

If the patient has a satisfactory nourishment status, begin with 100% of the requirement. If the patient is seriously malnourished, start with 80 % of the requirement and increase slowly to 100% over the course of three days.

The patient must be monitored closely in relation to

  • electrolytes (potassium, phosphate and magnesium).
  • infusion rate.
  • twenty-four hour urine sample and fluid balance should be calculated daily.
  • glucose in the blood and urine, and electrolyte in the blood should be examined daily at the start.
  • liver tests, kidney function tests and triglycerides should be taken examined at least once every week.

For TPN treatment longer than 1 month, vitamins and trace elements should be examined.

Follow-up

The patient's nutrition status should be monitored at follow-up visits after the end of treatment.

Antiemetisk behandling gyn

Kapitteloverskrift mangler!

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Bone Marrow Stimulation with G-CSF

General

Bone marrow stimulation with G-CSF (Neupogen®, Granocyte®) is only recommended for febrile neutropenia which does not respond to antibiotic treatment, severe neutropenia (granulocytes < 0.5 x 109 /L for more than 1 week), and in cases where it is necessary to administer curative treatment with sufficient dosage intensity.

Indications 

  • To maintain dosage intensity for curative treatment; when a reduction in dosage will significantly reduce the chance of cure.
  • As prophylaxis for treatments associated with a high risk for febrile neutropenia (> 40 %)
  • Febrile neutropenia that does not respond quickly to antibiotic treatment
  • Long-lasting neutropenia

Goal

  • Maintain treatment intensity

Preparation

The patient should be adequately informed about the treatment.

Implementation

  • The dosage of Neupogen® is 5 µg/kg daily. The treatment is initiated, at the earliest, 48 hours after the treatment is completed. The treatment continues for 10 days.
  • The dosage of Neulasta® is 6 mg subcutaneously administered 24 hours after chemotherapy is completed. The neutrophil cells are counted on day 15.
  • The subsequent course is started on day 21, if the neutrophil count is 0.5 or higher, and the patient has not had febrile neutropenia.
  • It is important not to postpone the treatment if the neutrophil count is 0.5 or higher. The neutrophil count will compulsory decline after ending Neupogen® stimulation. Low values at the start of treatment should not be alarming if the values during hospitalization have been high enough to avoid febrile neutropenia.
  • Stimulation late in the cycle should only be performed for long-lasting, severe neutropenia. At least 48 hours should pass after completed stimulation treatment before the next chemotherapy course  is started. In these cases, it is always important to check that the doses are correct and to recalculate GFR etc. Continuation of chemotherapy will either require a drastic dosage reduction or secondary prophylaxis with G-CSF.

 

Follow-up Care

It is of utmost importance that the patient is informed of the risk of infections associated with a low neutrophil count.

Patients at risk for developing  very low values, must be  informed to take their temperature if they feel unwell or  febrile. In case of  a temperature above 38 °C they should contact their doctor immediately.

Transfusions

General

Transfusions of blood components are often necessary for the patient to complete the planned cancer treatment.

Blood transfusions are appropriate for low hemoglobin (Hb) and thrombocyte transfusions for low thrombocytes (trc) which also poses a risk for serious bleeding.

Normal values

  • Hemoglobin 13.4–17 g/dl
  • Platelets 145–348 109/l

Indications

Blood transfusion

Assessment for a blood transfusion based on:

  • Hb/hct
  • symptoms/sign/function level
  • underlying disease (heart/lung, serious infection)
  • expected development of anemia (marrow function, current bleeding)
  • acute blood loss > 15% of total blood volume
  • Hb < 8.0 g/dl and symptom causing chronic anemia
  • Hb < 8.0 g/dl and reduced bone marrow production without sign of regeneration
  • Hb < 8.0 g/dl in perioperative period
  • Hb < 7.0 g/dl in patients without symptoms of other disease
  • Hb < 10.0 and receiving radiation therapy

Platelet transfusion

The patient is assessed for thrombocyte transfusion based on:

  • clinical status (bleeding, bleeding tendency, or fever/infection)
  • ongoing bleeding and thrombocytopenia < 50x19/l
  • degree of thrombocytopenia and cause of thrombocytopenia (reduced production or increased consumption)

Prophylactic platelet transfusion

  • For values < 10x109/l secondary to previous chemotherapy
  • Before invasive procedures
  • For spinal puncture and installation of central vein catheter, thrombocytes should be 30x109/l and 
  • Puncture biopsies (liver/kidney/tumor) > 40x109/l
  • For major surgeries, thrombocytes should be > 50x109/l. After surgery, thrombocytes should be monitored and transfusion repeated, if necessary.

Remember clinical evaluations: possible bleeding, other risk factors for bleeding, diagnosis, treatment, prognosis.

Goal

  • Complete the planned treatment
  • Ensure hemostasis 
  • Ensure adequate oxygen transport to peripheral tissue.
  • Maintain intravascular fluid volume for adequate circulations of vital organs

Definitions

Blood

For a blood transfusion for anemia, SAGMAN erythrocytes are used. One unit is obtained from 450 ml blood. Most of the plasma is removed and replaced with 100 ml SAGMAN solution (Saltwater-Adenine-Glucose-Mannitol). Hematocrit is about 0.60%.

Platelets

One unit contains 240-300 x 109 platelets and is prepared from blood donors with type O and A. In acute situations, the receiver's blood group is of minor importance.
Two kinds of platelet products are available:
  • Apheresis platelets produced from thrombophereses from one donor
  • Buffcoat platelets produced from buffy coat from 4 donors

All cellular blood products should be leukocyte filtered. Leukocyte filtration is done to remove antigen-presenting and virus-bearing cells. 99.99% of leukocytes in the unit are removed.

Radiation

Blood and thrombocytes are irradiated to a minimum of 25 Gy in the blood bank to eliminate T-lymphocytes.

This is done for:

  • Bone marrow transplant or stem cell transplant (1 month before or 3 months after HMAS until 1 year after allogeneic stem cell transplant)
  • For use of HLA-compatible platelet concentrations
  • For all transfusions from relatives
  • For use of fresh blood
  • For use of fludarabine

Preparation

Blood tests

Before the first blood transfusion, the following blood tests are performed:
  • Virus antigens
    • HCV
    • HBV
    • HIV
Every three days, and as needed, pre-transfusion tests are taken.

Compatibility

Erythrocyte concentration—Rh(D) negative products can usually be given to everyone while Rh(D) positive can only be given to Rh(D) positive receivers.

Thrombocyte concentration—Rh(D) negative girls and women in fertile ages who obtain Rh(D) positive thrombocyte products should be given a prophylaxis for Rh immunization. Boys/men and women who are over the fertile age may obtain thrombocytes regardless of Rh(D) type.

Implementation

Blood components should never be given together with other medications.
  • Premedication if the patient has reacted to previous transfusions.
  • Secure venous access
  • The blood product is checked to ensure the correct unit is given to the correct patient.
  • Use blood set with filter
  • Give SAGMAN over 1 hour and thrombocytes 20-30 minutes per unit.
  • Rinse the set with NaCl 9 mg/ml at the end of the infusion
  • Store the blood product bag for one day before discarding

Observations

The patient should be observed during the transfusion with emphasis on reactions. Most serious transfusion reactions occur within the first 20 minutes.

Symptoms of transfusion reaction:
  • chills
  • fever
  • feeling of heat in the face
  • breathing difficulty
  • itching
  • nervousness
  • fall in blood pressure
  • shock
Suspect/manifest blood transfusion reaction:
  • Stop transfusion immediately
  • Start treatment if necessary (intravenous fluid, adrenalin, steroids, oxygen, respirator)
  • Check blood bag and compatibility form. The residue should be sent to the blood bank.

Follow-up

Hemoglobin and thrombocytes are checked.

If poor effect of platelet transfusion, platelet value should be checked after approximately one hour. The value should have increased by approximately 30x109/l or more after a standard dose.

If the increase is drastically less, the cause may be:
  • Abnormally high consumption. This is an indication for more frequent transfusions.
  • Antigens against HLA or platelet-specific antigens. The patient must be examined in cooperation with the blood bank to find compatible donors.

Erythropoitin (EPO) for anemia

General

Anemia with hemoglobin < 11.0 mg/l is normal during chemotherapy. This will often lead to prominent fatigue. Anemia can be treated symptomatically with transfusion of erythrocytes, or bone marrow can be stimulated with erythropoitin (EPO).

Patients with chemotherapy-induced anemia will usually have sufficient iron storage, but some may need iron supplementation. 

Anemia should normally not cause postponement of treatment. It is quickly corrected by an erythrocyte transfusion – and treatment may then be started.

Indication

  • Patients with chemotherapy-induced anemia

Contraindications

  • Hypersensitivity to darbepoetin alfa, r-HuEPO or any of the additional ingredients.
  • Poorly-controlled hypertension
  • Reduced liver function (raised s-bilirubin). EPO is most likely eliminated via the liver. There is presently no toxicity data on patients with reduced liver function.
  • Some studies indicate a detrimental effect on patient survival by the use of EPO in cancer patients, and this treatment should be avoided for anemia in cancer patient for whom there is a curative goal with the treatment.

 

Goal

  • Reach hemoglobin level of 12–13 g/l

Preparation

  • Survey blood status
  • Evaluate iron status

Implementation

  • EPO is given in a dosage of 40,000 IE subcutaneously once daily
  • With use of Aranesp®, one dose of 500 μg subcutaneously is given every third week
  • For hemoglobin of 12 g/l, the dose is reduced by 25–50%, for example 300 μg every third week
  • For hemoglobin of 14 g/l, treatment is stopped until it has fallen to under 12 g/l where treatment is resumed with a 50% dose (for example, 300 μg or lower every third week). Repeated dosage reductions may be necessary. 
  • If the increase in hemoglobin rises above 2 g/dl (1.3 mmol/l) within 4 weeks, the dose should be reduced by 25–50%.

Assurance of efficient erythropoesis

  • Low s-iron and high ferritin implies iron deficiency. It is then recommended to give iron supplementation, for example slow-release iron tablets 100 mg x 2 daily for the first 4 weeks then once daily. If still no effect from this treatment, immediate action should be taken to find the cause.
  • Lack of iron, folic acid, or vitamin B12 reduces the effect of erythropoietin-stimulating drugs and should therefore be treated.
  • In the case of functional iron deficiency, iron storage is not released as needed and iron must be taken parenterally. Functional iron deficiency is characterized by normal or raised ferritin and normal serum iron/TIBC. 
  • Simultaneous infections, inflammatory or traumatic episodes, hidden blood loss, severe aluminum toxicity, or underlying hematological disease or bone marrow fibrosis can also impair erythropoietin response.
  • Reticulocyte count should be monitored as part of the evaluation.
  • If typical causes for no response have been excluded and the patient has reticulocytopenia, a bone marrow examination should be considered. If bone marrow assessment implies erythroaplasia (Pure Red Cell Aplasia – PRCA), testing with anti-erythropoietin antibodies should be done.

Follow-up

Follow-up of hemoglobin under EPO treatment is necessary because overstimulation can lead to polycytemia.

Smoking cessation in connection with cancer treatment

General

In patients treated with surgery, radiation and/or chemotherapy, the treatment efficacy may be affected by smoking. Smoking has an impact on both metabolism and pharmacokinetics.

Smoking may inhibit wound healing after surgery and increase the probability of surgical site infections. Because smokers generally have more mucus in the airways and are less able to remove it, they also may have a increased risk of serious lung complications during anesthesia. However, it is disputed whether or not it is beneficial to quit smoking directly prior to surgery and this should be considered in each case individually. (28,30-33). Smokers are more prone to stagnation of bronchial secretion than non-smokers and rapid postoperative extubation is important. 

Patients who continue smoking during radiation therapy have a lower risk of complete respons, development of secondary cancer, increased toxicity and several other side effects compared to non-smokers and smokers that quit before treatment. Continued smoking during radiation therapy is also associated with oral mucositis, impaired ability to taste, dry mouth, reduced voice quality, weight loss, cachexia, fatigue, pneumonia, bone-and soft tissue necrosis.

Tobacco may have an effect the metabolism and the mechanisms of chemotherapy and in this way may make the treatment less effective. Smokers undergoing chemotherapy may also experience a weakened immune system, increased rates of infection, exacerbation of common side effects, weight loss, cachexia, fatigue and cardiac or pulmonary toxicity. Some findings suggest that it may also apply to monoclonal antibodies.

Cancer patients who quit smoking before chemo- and radiation therapy get a total symptom burden equal to that of non-smokers, but those who continue to smoke state a higher symptom burden. Targeted measures in smoking cessation may increase quality of life and lead to less treatment interruptions.

A lot of patients wonder if there is any point to quit smoking after receiving a cancer diagnosis. tudies show that continued smoking is associated with increased treatment-related toxicity, increased risk of second primary cancers, reduced quality of life, reduced treatment effect and reduced survival in patients with cancer. This applies to both cancer diagnoses where smoking is a known causal factor, as with lung- and head and neck cancers and in cases where smoking has no known correlation with the diagnosis. Studies conducted on smoking and cancer diagnoses such as breast cancer, prostate cancer, colorectal cancer, esophageal cancer, cervical and ovarian cancer as well as leukemia and lymphoma cancers show that to continuation of smoking after a proven cancer diagnosis is associated with increased risk of mortality.

Studies support that quitting smoking improves cancer, and emphasizing the potential importance of targeted smoking cessation in cancerpatients during and after treatment. The link between tobacco and impact on cancer and cancer treatment is a complex matter.

Regarding the significance of the various components much is still unkown. When it comes to tobacco use in cancer treatment research is primarily done on the link between cigarette smoking and efficacy of cancer treatment. Nevertheless, it cannot be excluded that using other smokeless tobacco products such as snuff and chewing tobacco, may also impact the cancer treatment. According to international guidelines all tobacco use should be stopped during cancer treatment.


Benefits of smoking cessation and risks of continued smoking in patients with cancer
Quitting smoking results in the following benefits: Continued smoking results in a risk of :
  • improved treatment results.
  • less side effects
  • fewer infections
  • improved respiration and circulation
  • increased survival
  • reduced efficacy of treatment.
  • postoperative complications and longer recovery.
  • cardiovascular and respiratory complications.
  • recurrence of cancer, and secondary cancer.
  • shortened life expectancy.

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

Healthcare providers should convey evidence-based information to patients about how smoking affects cancer treatment, the risk of side effects and prognosis and also provide guidance and relevant treatment for smoking cessation.

Preparation

Patients require clear, formalized and fact-based guidance and continuous follow-up. Many patients want encouragement for smoking cessation early in the disease. Being hospitalized is a good opportunity because patients have access to support and help to reduce nicotine withdrawal symptoms and discomfort.

A patient recently diagnosed with cancer is often motivated to quit smoking and also receptive to conversations about how to do this. Motivation or willingness to quit often changes during the treatment, and use of tobacco and motivation should therefore be discussed at every consultation.

Clarifying the patient´s smoking habit is important. The time of day the patient lights their first cigarette says something about the degree of addiction. Making the patient aware of the situations in which he or she smokes most; at work, at home or in social settings, can help break unwanted patterns of behavior.

Implementation

The best and most direct approach to motivate the patient is telling that tobacco use will decrease the effectiveness of treatment and the most important thing the patient can do himself is to stop using tobacco.

  • Speak directly to the patient about how tobacco use may decrease the effectiveness of treatment.
  • Discuss smoking cessation with the patient at each visit.
  • Clarify any misunderstandings about the risks of tobacco use. Point out the importance of quitting.

Sometimes there may be misunderstandings about what kind of health risk smoking during and after cancer treatment may entail.

Advice to those who are not ready for smoking cessation
The smokers statement The response of health care professionals
Justifications
The damage from smoking is already done.
Some damage is done, but continued smoking will still damage your health and reduce the effects of treatment. Quitting smoking is more important now than ever.
This response tells the patient that it is not too late to quit smoking, and the effect of treatment will be positive.

I have reduced smoking.
That is great, and now you need to focus on quitting completely. What do you think keeps you from quitting altogether?
This response tells the patient the importance of quitting completely, as the benefits of quitting at baseline are documented.
This is not a good time to quit smoking.
The benefits of quitting are greatest now, before treatment begins. What is needed to make you feel ready to quit smoking?
 
This response make the patient aware of the fact that quitting smoking optimizes the cancer treatment.

Health professionals must assist the patient identifying realistic expectations and goals for smoking cessation. For some, it may feel easier to scale down the number of cigarettes than to quit completely. The patient should know that every puff affects their health, and that the total health benefits can only be achieved through smoking cessation. For patients unable to stop completely, a gradual reduction may be a step in the right direction.

The probability of success for smoking cessation significantly increases for those who receive professional help in combination with nicotine replacement therapy (NRT) or non-nicotine based products. For the best possible effect of NRT the patient needs professional guidance to find the right product and dosage. For some patients combining two products or receiving a higher dosage than recommended will give the best effect. Sometimes the product must be replaced during the treatment.

Treatment with nicotine replacement therapy

Topical products are patches (Nicorette®, Nicotinell®), chewing gum (Nicorette®, Nicotinell®), lozenges (Nicorette®, Nicotinell®), inhalator (Nicorette®) or a combination of these. These products contain nicotine and therefore reduce the withdrawal symptoms experienced after smoking cessation.

  • Patch: Nicorette® 5 mg,10 mg and 15 mg/16 hours up to 6 months or Nicotinell® 7 mg,14 mg og 21 mg/24 hours up to 3 months.
  • Chewing gum: Nicorette®/Nicotinell® 2 mg and 4 mg, 8-12 pcs/day up to 12 months.
  • Lozenges: Nicorette® 2 mg and 4 mg, typically 8-12 pcs/day, maximum respectively 15 pcs/day up to 9 months or Nicotinell® 1 mg and 2 mg, typically 8-12 pcs/day, maximum is respectively
    25 and 15 pcs/day up to 12 months.
  • Inhalator: Nicorette® 10 mg/dosage container, 4-12 pcs/day up to 6 months.

Combination therapy means combining patches with chewing gum, lozenges or an inhalator.

  • Nicorette® patch15 mg/16h and Nicorette chewing gum 2 mg. 5-6 chewing gums daily. Maximum 24 pcs/day
  • Nicorette® patch 15 mg/16h and Nicorette® inhalator 10 mg: 4-5 dosage-container daily. Maximum 8 pcs/day

Nicotine replacement therapy increases the chance of smoking cessation by 50 to 70% after six months. Two products used in combination increase the chance of smoking cessation compared to the use of only one product.

Side effects

  • Headache, dizziness, nausea, flatulence and hiccup.
  • Irritation in the mouth and esophagus using chewing gum/ lozenges/inhalator
  • Skin irritations while using patches.

Precautions

  • Precaution in acute cardiovascular disease, peripheral arterial disease, cerebrovascular disease, hyperthyroidism, diabetes mellitus, kidney- and liver failure and peptic ulcers.
  • Should not be used during pregnancy, unless the potential benefit outweighs the potential risk.
  • The products should not be used during breastfeeding.

Treatment with non-nicotine medications

Bupropion (Zyban®) is a selective reuptake inhibitor of dopamine and norepinephrine. The mechanism behind why the ability to refrain from smoking increases by using bupropin is unknown. A should be set for smoking cessation for the second week of treatment.

Bupropion increases the chance of smoking cessation after 6 months by nearly 70%.

Side effects

  • Dry mouth, nausea, insomnia, hypersensitivity reactions and seizures (convulsions)

Precautions

  • Contraindicated in people with disease that can cause convulsions,  people with substance abuse or other circumstances lowering the seizure threshold.
  • Depression, which in rare cases includes suicidal thoughts and – behavior including  suicide attempt.
  • Safety and efficacy have not been established for people under 18 years.
  • Should not be used during pregnancy.

Varenicline (Champix®) is a partial agonist by a subtype of nicotinic receptors. It has both agonistic activity with lower intrinsic efficacy than nicotine and antagonistic activity in the presence of nicotine.

A date for smoking cessation should be set. Treatment should start 1-2 weeks, or up to 35 days, before that date. The starting dose is 0,5 mg one time daily on days 1-3, then 0,5 mg two times daily on days 4-7, then 1 mg two times daily on day 8 and until the end of treatment. The treatment should last for 12 weeks.

Side effects

  • Nausea, sleep disturbances, headache, constipation, flatulence and vomiting

Precations

  • Links have been reported between the use of varenicline and an increased risk of cardiovascular events, suicidal thoughts, depression and aggressive and erratic behavior
  • Safety and efficacy have not been established for people under 18 years of age
  • Should not be used during pregnancy

Follow-up

If the patient experiences a relapse, it is important to inform them that this is completely normal, and encourage them to continue. If the most common measures do not work,
consideration should be given both to increase the NRP and to provide closer follow-up by health care providers.

Guidance in smoking cessation is described in the literature as brief and clear advice and then further follow-up with a telephone helpline offering treatment for addiction and behavior change/issues. It is not necessary for the patient to have decided to quit smoking in order to be referred to a quitline. If the patient agrees to receive a call from quitline, he or she will be followed up by a supervisor. Supervisors are bound by confidentiality, are up-to-date professionally and offer free follow-up counseling calls for up to a year.

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Follow-up after treatment of gestational trophoblastic disease

After mole evacuation

  • Serum hCG is monitored every other week until <1 IE/L for three repeated measurements. Serum hCG is then checked monthly for 6 months.
  • Birth control is recommended during the entire follow-up period after hcg is normalized (<1IE/L). Options include birth control pills, IUD or barrier method, or sterilization.

After chemotherapy for gestational trophoblastic disease

Serum hCG is checked:

  • before start of each course
  • weekly the first 3 months after treatment
  • every other week from 3-6 months after treatment
  • monthly from 6-12 months after treatment

Low risk patients do not need follow-up after one year. It is recommended the patient should use effective birth control for one year until after the first normal hCG (<1IE/L) measurement.

High risk patients have hCG testing as described above for 12 months, thereafter every 3 months for an additional 12 months. The patient is recommended to use effective birth control for 24 months after the first normal measurement of hCG.

Patients with placental-site trophoblastic tumors have hCG testing as described above for the first 2 years, then every 6 months for 5-10 years. Thereafter, the patient will have annual follow-up for life due to the risk for late recurrence. 

Pregnancy after gestational trophoblastic disease

Patients with normal hCG 8 weeks after evacuation are discouraged from becoming pregnant during the first 6 months. 

Patients with raised hCG 8 weeks after evacuation are discouraged from becoming pregnant during the first 12 months.

Pregnancy during the follow-up period often has a normal outcome. It is important the patient has follow-up with repeated hCG testing and early ultrasound to exclude a possible new molar pregnancy. New trophoblastic disease at the next pregnancy is rare, but may occur. For pregnancy after trophoblastic disease, a vaginal ultrasound should be performed early in the pregnancy. After the birth, the placental should be carefully inspected and sent for a histological examination.

Complications related to the disease:

  • Tumor bleeding
  • Uterine bleeding
  • Brain hemorrhaging
  • Hemoptysis

Complications related to treatment

  • Uterine perforation during evacuation/biopsy.

  • Respiratory insufficiency at the start of treatment in a patient with visible lung metastases.
  • Brain hemorrhage at the start of treatment of brain metastases.
  • Kidney, liver, and neurotoxicity from methotrexate.
  • Consider listing toxicities associated with EMA-CO. 

PROSEDYRER

Fatigue before, during, and after Cancer Treatment

General

There are many reasons why cancer patients feel fatigued. In many patients, the causes are synergistic. Cancer patients are often very sick during treatment periods and may experience extreme fatigue during intensive chemotherapy. It is also very important to be aware that fatigue is a symptom of many other medical conditions, both physical and psychological, which also affects cancer patients. Some known causes of fatigue associated with cancer and cancer treatment are: 

  • Cancer itself
  • An operation
  • Current or recently concluded chemotherapy
  • Current or recently finished radiation therapy
  • Severe anemia
  • Other symptoms such as pain and nausea 
  • Fever or infection
  • Too little fluid or food intake
  • Reduced lung function
  • Changes in sleep
  • Worries, anxiety, stress, or depression

For some of these conditions, such as infections, there is medical treatment available. Fatigue that occurs after an operation or during chemotherapy and radiation therapy will, for most, gradually disappear when strength is regained. If a patient was feeling healthy after treatment and all of the sudden experiences fatigue, they should contact their doctor. If a patient feels fatigue and at the same time feels stressed, worried, or down, they may be reluctant to speak to their doctor or health personnel about it. It is still recommended to talk about these problems. Talking about it may be therapeutic, and provides room for discussing measures with a qualified person with experience with patients that have the same problems. For cured patients experiencing chronic fatigue, it may be difficult to pinpoint a specific cause. Many of these patients experience improvement by changing their lifestyle to a lower tempo than before the diagnosis.

Definition

Everyone knows what it feels like to be tired, fatigued, or lethargic when sick. This feeling is the most common side effect of cancer and cancer treatment. A symptom is a condition or state that something is not right in the body. Other frequent symptoms associated with cancer and cancer treatment are reduced appetite and nausea. Most patients who experience fatigue associated with cancer say that the feeling does not improve with rest, and many describe a lack of energy or exhaustion.  

If fatigue arises during chemotherapy or radiation therapy, most patients experience that it will gradually go away when treatment is over and their strength is regained. This type of fatigue is considered acute. Improvement may take time depending on the intensity of treatment. Some patients experience that fatigue lasts for months, or even years. This is considered chronic fatigue. The ability to carry out daily activities, a lack of humor, health-related worries, a reduced capacity to carry out work functions, or less energy for family, can also accompany chronic fatigue. Most patients will find it difficult to be told by their doctor that they are considered healthy, while their friends and family expect them to be normal again, despite having a lack of energy and ability to perform activities they want to.  

For many, feeling fatigued is often accompanied by having difficulty concentrating, poor memory, and an increased need for sleep. Most patients will need more sleep than before they became sick. For many, sleep is not restful, and it may take time to "get going" in the morning. Many also experience that they quickly become drained of strength if they exert themselves, and that it takes a long time before regaining strength after exertion. Exertion in this context can mean both physically and mentally such as working on a task that requires concentration.

Preparation

Fatigue can occur in all phases of cancer illness. Some patients feel it before the diagnosis, and almost all patients experience fatigue during radiation therapy or chemotherapy. A minority of patients experience long term fatigue after cancer treatment is over and the disease is cured. Patients who cannot be cured will almost always feel tired, worn-out, and exhausted. The degree of fatigue in these patients varies depending on the cancer type, spreading, and other symptoms of the disease.

The patient should be given necessary information on both causes of fatigue and measures he/she can take.

Implementation

General measures that can reduce feeling tired and fatigued

Following suggestions are meant as general advice that may not necessarily apply to everyone in all situations. This advice is based on results from studies, experiences from cancer patients, and recommendations from experts. Each patient should assess what works for them. It is recommended to express concerns and seek advice for what measures you can take and what you should avoid.

General advice
  • Try to live as "normal" as possible.
  • Try to plan your day to include time to rest.
  • Take many small breaks during the day instead of a few long ones.
  • Rest after strenuous activity.
  • Plan your daily activities and do those that are most important for you.
  • Set realistic goals for yourself and try to be happy with those you accomplish.
  • Try to recognize activities that make you especially tired/fatigued and limit them, or spread them out over longer intervals. 
  • Try to accept that you do not have the energy to do the things you could previously.
  • Assess what is important for you to do yourself and what you can allow others to do.
  • Assume you will be tired after something strenuous even if you experience the activity as positive.

Physical activity and exercise

Exercise and physical activity that is appropriate for you will reduce the feeling of fatigue. Regular exercise is the most effective measure against chronic fatigue in cancer patients. Nevertheless, both too much and too little exercise can worsen fatigue, therefore, it is important to find a level (frequency and intensity) that suits you. You should never exercise so intensely that you must stop a session or exercise period because you are exhausted. Remember that daily form varies for everyone and adjust your exercise routine accordingly. Make long-term goals (months) and gradually increase activity, and carefully for a period. 

  • Activities such as walking, biking, swimming, dance, and aerobics are recommended.
  • Light exercise periods at regular intervals are better than intense, sporadic periods.
  • Always start with a slow tempo and increase gradually before finishing with a slow tempo again.
  • Always sit down and rest after exercise but try not to lay down and sleep.
  • Physical therapists and sport pedagogs can provide advice on exercises that are right for you. The principles are the same for all exercise, but it should be adjusted for your energy level.  

Sleep

Many cancer patients with chronic fatigue have sleep pattern disturbances. It is important to maintain a normal rhythm even if you feel like sleeping during the day.

  • Try to wake up at the same time every day and keep a regular bedtime.
  • Avoid too much activity right before bedtime.
  • Try not to sleep during the day because this will disturb your biological rhythm.
  • But, a short afternoon nap may be energizing!
  • Rest during the day by relaxing in a good chair, but try not to fall asleep.
  • Speak to your doctor about lasting sleep disturbances.

Nutrition

Having a reduced appetite or intake of food can also result in a lack of strength and energy. We recommend eating healthy food regularly, and to follow the national guidelines on nutrition. Special diets or supplements do not improve fatigue unless there is a deficiency.

Work situation

Some patients do not have the strength to continue working, or they must reduce their hours because of chronic fatigue. Consulting with a social worker may be beneficial for guidance regarding your work situation, your welfare rights, and financial situation. 

Some adjustments that you and your employer can make:

  • Discuss the possibility for more simple or easier tasks, especially if you have a physically demanding profession.
  • Assess the possibility of reducing your hours.
  • Remember to take regular breaks also at work, if possible.
  • Assess the possibility of flexi-time to work during the hours you have energy, as well as the possibility of working from home.

Care for children

Caring for children or adolescents may be very difficult when you are fatigued or lack energy and strength. There are, however, some measures you can take:

  • Explain to your children that you are tired and are not able to do as much as you used to.
  • Discuss what the children can help you with and allow them to take part in household chores.
  • Try to establish permanent household chores for all family members.
  • Try to do activities that suit you that do not require too much energy, and can be performed without too much exertion. 
  • Ask and accept help from others for driving to and from activities, school, etc. if this relieves you.

Drug therapy

In Norway, there is currently no specific drug therapy for chronic fatigue associated with cancer. If the fatigue is due to specific conditions, this is of course treated with medication, if possible. Sometimes, such treatments improve the fatigue, but other times they do not. Examples of treatment that often reduce fatigue are treatment for infections and depression. 

Treatment with medications that stimulate production of red blood cells is not recommended for cancer patients due the the danger of serious side effects.

Follow-up

Information about fatigue

Healthcare workers in cancer care will often have knowledge about fatigue and cancer. Most general care physicians have general experience with fatigue but meet relatively few cancer patients. There is a lot of information available on the internet of varying quality. Below is a list of web adresses and some literature. Be aware that you may find opposing advice because knowledge on treatment especially, is limited.

Some articles/books:

  • Armes J., m.fl. (2004). Fatigue in cancer. Oxford University Press.
  • Berger A.M., m.fl. (2009). NCCN Clinical Practice Guidelines in Oncology. Cancer-Related Fatigue. www.nccn.org
  • Patarca-Montero R. (2004). Handbook of cancer-related fatigue. Haworth Medical Press