Gynecologic cancer

Gynecologic oncology includes malignant tumors originating from the female genitalia including:

• Vulva
• Vagina
• Uterus 
• Adnexa
  • Ovary
  • Fallopian tubes
  • Broad ligament of the uterus
• Tumors originating from the placenta (trophoblastic tumors)

Incidence

It was estimated about 98,000 new cases of gynecologic cancers in the United States during 2015, according to American Cancer Society (4).

PROSEDYRER

Gyn_BEP

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Gyn_cisplatin

Gyn_Cisplatin_Caelyx_Hypersensitivitetskur

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Gyn_Caelyx

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Gyn_Cisplatin Etoposid

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Gyn_Cisplatin_Gemcitabin

Gyn_Cisplatin Paklitaksel

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Gyn_Cisplatin ukentlig

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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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Gyn_Doksorubicin

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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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Gyn_EP_5_dager

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Gyn_Gemcitabin

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Gyn_Karboplatin

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Gyn_Karboplatin Caelyx

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Gyn_Karboplatin_Docetaxel

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Gyn_Karboplatin Epirubicin

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Gyn_Karboplatin_Etoposid_3_dager

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Gyn_Karboplatin_Gemcitabin

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Gyn_Karboplatin Paklitaxel

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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.

Gyn_Paklitaxel_hver_3_uke

Gyn_Paklitaksel_Topotekan

Gyn_Paklitaxelukentlig

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Gyn_Topotecan

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