Treatment of Nausea Induced by Chemotherapy

Medical editor Gustav Lehne MD
Oncologist
Oslo University Hospital
Norway

General

The majorities of chemotherapy drugs are emetic to varying degrees and may cause nausea and vomiting. Today, there are efficient antiemetic drugs that can significantly reduce the side effects.

Other factors that can aggravate or prolong the presence of nausea and vomiting are: pain, anxiety, electrolyte disturbances, constipation, dyspepsia, and ulcers.

There is a distinction between acute nausea, which occurs within the first 24 hours, and late nausea, which occurs later than 24 hours after the treatment.

Acute nausea can be effectively treated with 5HT3-antagonists (ondansetron, tropisetron, palonosetron), and possibly combined with steroids. Dopamine antagonists (metoklopramid, metopimazine) also have some effect on acute nausea. If this treatment is not effective, it may be improved with aprepitant.

If standard prophylaxis and treatment of nausea is not satisfactory, other nausea regimens should be tried.

Indication

Nausea induced by chemotherapy drugs.

Goal

Prevention and treatment of nausea and vomiting.

Definitions

Chemotherapies according to emetic potential
High emetogenicity Group 1	Moderate emetogenicity Group 2	Low/minimal emetogenicity Group 3
All cisplatin-containing regimens (CiFu, GemCis, BEP, TIP, VIP, PV, AP, EDP, DHAP, ECX, weekly dose cisplatin, and others)	BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosfamide, vincristine, prokarbazine, prednisolone)	Doxorubicin/epirubicine weekly dose
Doxorubicin/ifosfamide	Bendamustine	Docetaxel
FEC-60 og FEC-100 (fluorouracil, epirubicin, cyklophosfamide)	Carboplatin	ENAP (etoposide, mitoxsantrone, cytarabine, prednisolone)
ABVD (doxorubicin, bleomycin, vinblastine, dakarbazine	Carboplatin/pemetrexed	FLv (fluorouracil)
FOLFIRINOX	Carboplatin/vinorelbine	FuMi (fluorouracil, mitomycin)
	CHOP (cyclophosfamide, doxorubicin, vincristine, prednisolone)	Gemcitabine
	CHOEP (cyclophosfamide, doxorubicin, vincristine, etoposide, prednisolone)	Methotrexate weekly dose
	Dakarbazine	Navelbine
	ECO/ACO (epirubicin/doxorubicin, cyclophosfamide, vincristine)	Paclitaxel
	EOX (epirubicin, oxaliplatin, capecitabine)	Pemetrexed
	EPOCH-F (etoposide, prednisolone, vincristine, cyclofosfamide, doxorubicin, fludarabine)
	EPOCH-F (etoposide, prednisolone, vincristine, cyclophosfamide, doxorubicin, fludarabine)
	FLIRI (fluorouracil, irinotecan)
	FLOX (fluorouracil, oxaliplatin)
	Gemcitabine/carboplatin
	HD-Cytarabine
	HD-Methotrexate
	IGEV (ifosfamide, gemcitabine, vinorelbine)
	IME (ifosfamide, methotreksate, etoposide)
	Irinotecan
	Streptozocin
	Vorphase (cyclophosfamide)

References

Lehne G, Melien Ø, Bjordal K, Aas N, Mella O. Kvalme og oppkast ved cytostatikabehandling i: Dahl O, Christoffersen T, Kvaløy S, Baksaas. Cytostatic Medication cancer treatment. 7. edition. Oslo. Department of Pharmacotherapeutics and The Norwegian Cancer Society, 2009, p 119-130.

Preparation

Nausea regimens are selected according to the emetogenicity of the relevant drugs.

Inform about the risk for and treatment of nausea.
In the event of anxiety or conditional nausea, give tranquilizers if necessary.

Implementation

Start with an optimal antiemetic regimen starting with the first cycle of chemotherapy in order to counteract the amplification of the nausea that often occurs with a new treatment.
Start the oral antiemetic regimen 1-2 hours before chemotherapy and approx. 15-30 minutes before an intravenous injection.
If the patient is already nauseous, the medication should be administered parenterally or rectally.

Antiemetic regimens

Mildly emetic chemotherapy

Metoclopramide 10 mg is given intravenously before treatment with cytostatic agents.
Metoclopramide 10 mg is given orally uptil 3 times.

Moderately emetic chemotherapy

Ondansetron 8 mg orally 2 x daily. In the event of nausea before treatment, give ondansetron intravenously. If this has little effect, try ondansetron 8 mg x 3 or change to a 5HT3-antagonist, for example, tropisetron 5 mg orally/intravenously or palonosetron 250 µg intravenously.

Highly emetic chemotherapy, or if other treatment does not help

For highly emetic chemotherapy drugs, or if other treatment is not adequate, a 5HT3-antagonist can be given orally or intravenously. It should be combined with dexamethasone 8-16 mg intravenously ½-1 hour before treatment, and further, 8 mg x 2 intravenously or orally on the first day.

In addition, dopamine antagonists may be given, for example, metoclopramide 10 mg x 3.

In some cases, traditional nausea treatment is not sufficient. In this case, the patient can be treated with aprepitant. Aprepitant is used for highly emetic regimens and for patients where the usual antiemetic treatment has failed during moderate emetogenic treatment. Aprepitant is given orally 1 hour before chemotherapy and is combined with dexamethasone and 5HT3-antagonists: 125 mg capsules orally on day 1, then 80 mg orally on days 2-5, depending on the duration of the treatment. Aprepitant can enhance the effect of taxane and etoposide, as well as vinorelbine, and can reduce the effect of warfarin.

The regimen is repeated daily if highly emetic treatment is given over a number of days.

Delayed nausea

Aprepitant in combination with dexamethasone and 5HT3-antagonists is preferable if there is a high risk of delayed nausea and vomiting. This is offered especially to patients who have previously experienced delayed nausea.

Conditional nausea

In the event of conditional nausea, diazepam or other tranquilizers may be considered. Diversion or desensitization can be tried in more serious cases.

Follow-up

Ondansetron can have a constipating effect. Use of a laxative for several days should be considered.