A common chemotherapy regimen gets reclassified as high risk for emesis; a new approach is recommended to tackle treatments with high emetic potential; and a particular antiemetic drug is now preferred for patients at moderate risk – these are among the changes to clinical practice guidelines from the American Society of Clinical Oncology.
The guidelines also include new recommendations for preventing nausea and vomiting associated with radiation treatment.
Treatment-related nausea and vomiting is reported by more than half of patients. If it is severe enough, dehydration and other adverse health effects can result and can limit treatment and patient outcomes.
One key change to the guidelines involves the chemotherapeutic agents anthracycline and cyclophosphamide, each of which carries a moderate risk for emesis if used alone. However, when the two are prescribed together, the patient’s risk for emesis is high. This upstaging to high risk is important, the authors wrote, because these agents are commonly combined, particularly to combat breast cancer and non-Hodgkin’s lymphoma.
For this and other high-risk therapies, the guidelines now recommend use of newer antiemetics. For example, a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist in combination with dexamethasone and a neurokinin 1 (NK1) receptor antagonist is suggested to prevent significant nausea and vomiting.
In addition, a new NK1 receptor agonist, fosaprepitant (Emend, Merck), is available as a new, 1-day intravenous formulation of aprepitant, which needs to be infused over 3 days. The therapeutic equivalence of these two drugs was demonstrated in a large trial (J. Clin. Oncol. 2011;29:1495-501) and thus either one is appropriate, according to the guidelines. The briefer administration of fosaprepitant "may represent a more convenient or feasible option for some patients," the guideline update committee noted.
These and other revisions are based on new research findings since the last update to the guidelines in 2006. The 14-member committee reviewed 37 randomized, controlled trials, searched the Cochrane Collaboration Library, and evaluated presentations from the annual meetings of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer.
The antiemetic recommendations are categorized according to the emesis risk of the chemotherapy regimens. For example, palonosetron (Aloxi, Helsinn Healthcare), is listed as preferential for moderate–emetic-risk regimens when given on day 1 and when combined with dexamethasone on days 1-3. If palonosetron is not available, the authors state that granisetron or ondansetron may be substituted.
In addition, a single, 8-mg dexamethasone dose alone is appropriate before the first dose of cancer-fighting agents associated with a low risk for emesis. And no antiemetic prophylaxis is necessary for chemotherapy regimens deemed to have minimal risk, according to the guidelines. These recommendations have remained the same since the last guideline update.
Recommendations regarding radiation treatment are likewise stratified by risk for emesis. For example, when a radiation course carries a high emetic risk, the guidelines recommend a 5-HT3 agent prior to each fraction and for at least 24 hours following completion of radiotherapy. The update committee dropped the recommendation that this therapy be given with or without a corticosteroid and added that a 5-day course of dexamethasone is indicated during fractions one to five.
For moderate-risk radiation therapy, a 5-HT3 antagonist before each fraction throughout radiotherapy remains the recommendation, with addition of a short course of dexamethasone during fractions one to five.
And for low-risk radiotherapy, the committee recommends a 5-HT3 antagonist alone as either prophylaxis or rescue. This represents a change from the 2006 recommendation for administration of a 5-HT3 agent before each fraction.
For minimal-risk radiotherapy, the new recommendation is for rescue therapy with either a dopamine receptor antagonist or a 5-HT3 antagonist. This is similar to the 2006 recommendation for a dopamine or serotonin receptor antagonist on an as-needed basis.
When rescue antiemetic therapy is given, the authors recommend that prophylactic treatment be continued until radiotherapy is completed.
Other major themes of the guidelines include a need for continued symptom monitoring and a recognition that clinicians tend to underestimate the incidence of nausea; therefore, nausea is often less well controlled than emesis.
Some members of the update committee had the following financial disclosures: Dr. Paul Hesketh is a consultant to Eisai, GlaxoSmithKline, Helsinn, and Merck; Dr. Mark G. Kris is a consultant to Sanofi-Aventis and GlaxoSmithKline; and Dr. Petra C. Feyer is a consultant to GSK and Merck. Dr. Rebecca Clark-Snow receives honoraria from Merck, and Dr. Feyer receives honoraria from Merck, GSK, and Roche.