Guidelines for Antiemesis Emphasize Prophylaxis

FORT LAUDERDALE, Fla--The new NCCN practice guidelines on antiemesisin patients receiving chemotherapy are divided into four categories basedon the emetogenic potential of the chemotherapy regimen, ie, high, moderate,low, and unlikely, and further divided into primary treatment, breakthroughtreatment, and use in subsequent chemotherapy cycles. The guidelines alsocover antiemesis for radiation-induced nausea and vomiting.

In presenting the preliminary guidelines on antiemesis at the NCCN'ssecond annual conference, David Ettinger, MD, panel chairman, stressedthat the cost of antiemetic drugs should not be a factor in choosing prophylaxis,and that cost was not a consideration in writing the guidelines.

NCCN Antiemesis Practice Guidelines Panel Members

David Ettinger, MD
Chairman, The Johns Hopkins
Oncology Center

Steven Huber, PharmD
M.D. Anderson Cancer Center

Mark Kris, MD
Memorial Sloan-Kettering Cancer Center

Michael Levy, MD
Fox Chase Cancer Center

Bob McNulty, PharmD
Ohio State University

Kimberly Rogers Noonan, RN
Dana-Farber Cancer Institute

Lisa Stucky-Marshall, RN
Northwestern Memorial Hospital

Susan Urba, MD
University of Michigan

"The cost of these drugs is very institution and region specific,"he said. "It depends on what other drugs the institution is buyingfrom that particular pharmaceutical company. So we've tried to define antiemesisregimens that are equivalent in efficacy and safety, and I think each institutionthen has to figure out what is best for its particular situation."

He pointed out that the cost of the newer 5-HT3 receptor antagonistshas come down tremendously in the last few years. "A 32-mg dose ofIV ondansetron costs the pharmacy roughly $40 today versus about $300 onlya couple of years ago," Dr. Ettinger said.

He strongly encouraged use of the 5-HT3 receptor antagonists for prevention,noting that "one episode of vomiting is too many." In a Gallopsurvey of cancer patients who had received chemotherapy and antiemeticsin the last three years, 75% of respondents said they had vomited duringtheir therapy. "The truth is they may have vomited only once or twice,but from their standpoint, it was still terrible," he noted.

He urged physician to "do the right thing and make sure you'regiving effective therapy. Do not let cost tell you what dose to prescribe."He cited a British Cancer Journal article from 1993 comparing the costof one emetic episode versus controlled emesis, "and it was about2:1."

For highly emetogenic chemotherapy regimens, the guidelines recommendoral granisetron (Kytril) plus dexamethasone with or without lorazepamas primary therapy.

Dr. Ettinger pointed out that oral ondansetron (Zofran) was not includedfor use as first-line prophylaxis for highly emetogenic chemotherapy regimensbecause of the lack of clinical trial data that it is effective. However,he said, "there is no doubt that it is effective; we just don't havesufficient data to include it in these evidence-based guidelines."

Intravenous ondansetron or granise-tron (given with dexamethasone andwith or without lorazepam) is recommended for patients who cannot tolerateoral medications. He added that the guidelines give a wide dosage rangefor ondansetron in this setting, and that "it could even be widerif we had included the 8 mg dose."

Another panel member, Mark Kris, MD, of Memorial Sloan-Kettering CancerCenter, commented that the 8 mg dose, although not widely used in the UnitedStates for highly emetogenic chemotherapy, is a standard ondansetron dosein Europe.

"Two multicenter randomized trials that compared 8 mg to 32 mgof IV ondansetron in patients receiving cispla-tin showed identical results,"Dr. Kris said, and a comparison of 8 mg of IV ondan-setron with 3 mg ofIV granisetron also gave identical results when each was combined withdexamethasone. Multicenter trials have also shown the equivalence of 1mg and 3 mg doses of granisetron.

"When these guidelines have reached their next edition, they willbe modified to reflect the effective range of doses that the literaturesupports," Dr. Kris said.

For moderately emetogenic regimens, the recommendations are essentiallythe same except that a lower dose of IV on-dansetron (8 mg to 24 mg) issuggested for patients who cannot take oral drugs.

For drugs that cause delayed emesis, the guidelines recommend metoclopra-mideplus dexamethasone; or ondanse-tron plus dexamethasone, 8 mg bid for twodays followed by 4 mg bid for an additional two days.

Dr. Kris reiterated that this is meant to be used as prophylaxis forall patients receiving high-dose cisplatin or cyclophosphamide. "Itis not for people who fail antiemetic therapy," he said.

The guidelines provide six options for the treatment of breakthroughvomiting (within the first 24 hours after chemotherapy), Dr. Ettinger said,"because each of the member institutions had its own pet drug. Andif you look at the literature, these are the various drugs that have someeffect as breakthrough treatment."

Dr. Ettinger pointed out the difficulty physicians face when antiemesisproves ineffective in subsequent chemotherapy cycles, particularly whenthe chemotherapy regimen is being given with curative intent and nauseaand vomiting cannot be controlled. "I think, in that situation, thepatient is going to want to bite the silver bullet, so to speak, and continuetreatment." He urged the physician to "use any tricks of thetrade, including, maybe, heavy sedation, to get the patient through thechemotherapy."

With low-level chemotherapy-induced nausea and vomiting, the treatmentof choice is dexamethasone. Although a number of other options are available,"I think dexamethasone has been shown to be effective in this setting,"Dr. Ettinger said. For those drugs that are unlikely to cause any nauseaand vomiting, no initial treatment is recommended.