Nausea and Vomiting

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Side Effects of Cancer

Overview

Nausea and/or vomiting are frequent side effects of chemotherapy and radiation therapy. While these used to be among the most debilitating side effects of chemotherapy, the development of new and more effective antiemetic (anti-vomiting) drugs has provided relief and many patients no longer experience nausea or vomiting at all.

What is nausea and vomiting?

Nausea is feeling queasy or sick to your stomach, like you’re going to throw up. Vomiting is emptying your stomach by throwing up. Nausea and/or vomiting are frequent side effects of chemotherapy and radiation therapy. Chemotherapy-induced nausea and vomiting can be acute(within the first 24 hours), delayed (vomiting that occurs after 24 hours) and/or anticipatory. Anticipatory vomiting is a learned response, which means it happens in response to a stimulus, chemotherapy. With this type of nausea and vomiting, the symptoms usually occur afterinitial exposure to chemotherapy drugs and before subsequent treatments.

Why do cancer patients experience nausea and vomiting?

A specific location in the brain controls emesis (vomiting), called the vomiting center. Emesis occurs when the vomiting center receives a signal from the brain, the gastrointestinal tract, the heart and/or the inner ear, which detects motion. Chemotherapy causes the release of a substance called serotonin (5-HT), and of other chemicals in the small intestine, which through a series of signals stimulate the vomiting center in your brain to induce emesis.

How can nausea and vomiting be prevented?

The best way to treat nausea and vomiting is to prevent it from occurring in the first place. Many new and improved medicines for controlling nausea and vomiting, called antiemetics, have been developed over the last several years. These drugs block the signal in the brain that causes nausea and vomiting. As a result of widespread use of antiemetics, nausea and/or vomiting is not as severe and does not occur as frequently as in the past. There are many different kinds of antiemetics and you may need to try more than one before finding a prescription that works for you.

5-HT3 inhibitors: The 5HT-3 Inhibitors are the most effective antiemetics and constitute the single greatest advance in the management of nausea and vomiting in patients with cancer. These drugs are designed to block one or more of the signals that cause nausea and vomiting. The most sensitive signal during the first 24 hours after chemotherapy appears to be 5-HT3. Blocking the 5-HT3 signal is one approach to preventing acute emesis, or emesis that is severe, but relatively short-lived. Antiemetics that block 5-HT3, called 5-HT3 inhibitors, are the most effective agents developed to date for preventing emesis and are available to be administered orally or intravenously. The newest 5-HT3 inhibitor, Aloxi® (palonosetron), has a distinct advantage over the other 5-HT3 inhibitors because in addition to preventing acute nausea and vomiting, Aloxi® also prevents delayed nausea and vomiting, which occurs during the 2-5 days after treatment. [1],[2] Aloxi® is the only drug in its class that is approved by the FDA for the treatment of delayed nausea and vomiting.

Other examples of FDA-approved 5-HT3 inhibitors include:

  • Dolasetron (Anzemet®)
  • Granisetron (Kytril®)
  • Ondansetron (Zofran®)

Other drug therapy approaches: Other drugs commonly used to prevent or treat nausea and vomiting, either alone or in combination with antiemetics, include:

  • Corticosteroids (dexamethasone, methylprednisolone, Prednisone®, and others)
  • Dronabinol (Marinol®)—stimulates appetite and controls nausea
  • Prochlorperazine (Compazine®)
  • Benzodiazapines (Valium® and others)—may help control anticipatory nausea
  • Aprepitant (Emend®): Aprepitant is part of a three-drug therapy that works to prevent delayed nausea and vomiting. Aprepitant is not used to treat nausea and vomiting that you already have; it must be taken before the symptoms occur to be effective.[3] [4] This is because it blocks the NK1 receptor in the brain which helps with nausea and vomiting that persists beyond 2 days after treatment.

What can I do to help manage nausea and vomiting?

There are several things you can do to prevent nausea and vomiting. First and foremost, make sure you receive and take your antiemetics as your doctor has ordered. Let your doctor or nurse know if your drugstore does not have them, you cannot afford to pay for them, or you are not sure how to take them. Also, call your doctor if you experience any of the following:

  • You have vomiting and cannot take your medication
  • Your antiemetics help reduce your nausea and vomiting, but not as much as you would like. The dose may have to be changed or the doctor may change you to a different antiemetic.

In addition to taking your medication, the following general suggestions may help you prevent or control nausea and vomiting:

  • Try eating foods and drinking beverages that have been easier for you to take or have made you feel better when you had the flu, morning sickness or were nauseated from stress. These might be bland foods, sour candy, pickles, dry crackers, ginger ale, flat soda or others. Eat small, frequent meals (5-6), instead of 3 large meals each day.
  • Do not eat fatty or fried foods, very spicy foods or very sweet foods.
  • If possible, have somebody else make the meals when you are nauseated.
  • Do not eat your favorite foods when you are nauseated.
  • If you have nausea and vomiting only for a few days after chemotherapy, cook and freeze several meals that you can reheat during times when you are nauseated.
  • Eat foods that are at room temperature or cold. The smells from hot foods may make your nausea worse.
  • Keep your mouth clean; brush at least twice a day.
  • Consider shakes or liquid nutritional supplements to help maintain your nutrition.
  • Ask your doctor or nurse about using acupressure (BioBands) on your wrists, which may help to decrease your nausea.
  • Anticipatory nausea associated with chemotherapy is best controlled with relaxation techniques.
  • Ask your doctor or nurse if they can help you learn a relaxation exercise. This might make you feel less anxious and more in control, and decrease your nausea.

What if I have anticipatory nausea and vomiting?

Anticipatory nausea and vomiting is poorly controlled with standard antiemetic treatment. In some clinical studies, drugs that treat anxiety (benzodiazepines) have provided some relief. A number of non-drug approaches, also called cognitive and behavioral intervention, may help. These include:

  • Systematic desensitization
  • Distraction from the negative experience with guided imagery or relaxation
  • Elimination of consistently repeating patterns
  • Manipulation of the setting and personnel associated with chemotherapy administration
  • Biofeedback
  • Blocking taste sensation with another strong taste (e.g., lemon)

Are some treatments more likely to cause nausea and vomiting?

Certain chemotherapy drugs are more likely to cause nausea and vomiting than others. Chemotherapy drugs are classified as mildly, moderately or highly likely to cause nausea and vomiting.

The table below lists the degree of nausea and vomiting patients would experience without effective antiemetic drugs. High-dose chemotherapy is almost always associated with a high probability of nausea and vomiting and appropriate antiemetics are indicated. Most chemotherapy treatment regimens use more than one drug. The degree of nausea and vomiting produced by a combination chemotherapy treatment regimen is typically greater than the amount of nausea expected from the single drug producing the greatest amount of nausea and vomiting.

Drugs

Amount of nausea/vomiting
Trade Name Generic name

None

Mild

Mod

High
Chemotherapy drugs
5-FU fluorouracil

X
Adriamycin® doxorubicin

X

X
Alkeran® melphalan

X
Agrylin® anagrelide

X
Aredia® pamidronate

X
Arimidex® anastrozole

X
Aromasin® exemestane

X
Bexxar® tositumomab iodine 131

X
BiCNU® carmustine

X
Blenoxane® bleomycin

X
Campath® alemtuzumab

X
Camptosar® irinotecan

X
Casodex® bicalutamide, nilutamide

X
CeeNU® lomustine

X

X
Cerubidine® daunomycin

X

X
Cosmegen® dactinomycin

X

X
Cytadren® aminoglutethimide

X
Cytosar-U® cytarabine

X

X
Cytoxan® cyclophosphamide

X

X
DaunoXome® daunorubicin

X

X
dexamethasone dexamethasone

X
Doxil® liposomal doxorubicin

X
DTIC-Dome® dacarbazine

X
Ellence® epirubicin

X

X
Eloxatin® oxaliplatin

X
Elspar® asparaginase

X

X
Emcyt® estramustine

X
Ergamisol® levamisole

X
Evista® raloxifene

X
Faslodex® fulvestrant

X
Femara® letrozole

X
Floxuridine floxuridine

X
Fludara® fludarabine

X

X
Gemzar® gemcitabine

X
Gleevec® imatinib mesylate

X
Hexalen® hexamethylmelamine

X
Hycamtin® topotecan

X
Hydrea® hydroxyurea

X
Idamycin® idarubicin

X

X
Ifex® ifosfamide

X

X
Iressa® gefinitib

X
leucovorin leucovorin

X
Leukeran® chlorambucil

X
Leustatin® 2-chlorodeoxyadenosine (cladribine)

X
Lupron® leuprolide

X
Matulane® procarbazine

X

X
methotrexate methotrexate

X

X

X
Mithracin® plicamycin

X
Mustargen® mechlorethamine

X

X
Mutamycin® mitomycin

X
Myleran® busulfan

X
Mylotarg® gemtuzumab ozogamicin

X
Navelbine® vinorelbine

X
Nipent® pentostatin

X

X
Nolvadex® tamoxifen

X
Novantrone® mitoxantrone

X
Oncaspar®

X

X
Oncovin® vincristine

X
Paraplatin® carboplatin

X
Photofrin® porfimer sodium

X
Platinol® cisplatin

X
prednisone prednisone

X
Purinethol® mercaptopurine

X
Quadramet® samarium 153 lexidronan

X
Taxol® paclitaxel

X
Taxotere® docetaxel

X

X
Temodal® temozolomide

X
Thalomid® thalidomide

X
Thioguanine 6-thioguanine

X
Thioplex® thiotepa

X
Trisenox® arsenic trioxide

X
Valstar® valrubicin

X
Velban® vinblastine

X
Velcade® bortezomib

X
VePesid® etoposide

X
Vesanoid® tretinoin

X
Vumon® teniposide

X
Xeloda® capecitabine

X
Zanosar® streptozocin

X
Zevalin® Ibritumomab tiuxetan

X
Biologic Agents
Aranesp® darbepoetin alfa

X
Herceptin® trastuzumab

X
Intron®A interferon

X
Leukine® sargramostim

X
Neulasta® pegfilgrastim

X
Neumega® oprelvekin

X
Neupogen® filgrastim

X
Procrit® epoetin alfa

X
Proleukin® aldesleukin

X
Rituxan® rituximab

X

References

[1] Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003;98:2473-2482.

[2]Gralla R, Lichinitser M, Van der Vegt, S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-1577.

[3] Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin–the Aprepitant Protocol 052 Study Group. Journal of Clinical Oncology 2003 Nov 15;21(22):4112-9.

[4] de Wit R, Herrstedt J, Rapoport B, Carides AD, et al. Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. Journal of Clinical Oncology. 2003 Nov 15;21(22):4105-11.