Guidelines for Antiemesis Emphasize Prophylaxis

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

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

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

He pointed out that the cost of the newer 5-HT3 receptor antagonists has come down tremendously in the last few years. "A 32-mg dose of IV ondansetron(Drug information on ondansetron) costs the pharmacy roughly $40 today versus about $300 only a 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 Gallop survey of cancer patients who had received chemotherapy and antiemetics in the last three years, 75% of respondents said they had vomited during their 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're giving effective therapy. Do not let cost tell you what dose to prescribe." He cited a British Cancer Journal article from 1993 comparing the cost of one emetic episode versus controlled emesis, "and it was about 2:1."

For highly emetogenic chemotherapy regimens, the guidelines recommend oral granisetron(Drug information on granisetron) (Kytril) plus dexamethasone(Drug information on dexamethasone) with or without lorazepam(Drug information on lorazepam) as primary therapy.

Dr. Ettinger pointed out that oral ondansetron (Zofran) was not included for use as first-line prophylaxis for highly emetogenic chemotherapy regimens because 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 have sufficient data to include it in these evidence-based guidelines."

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

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

"Two multicenter randomized trials that compared 8 mg to 32 mg of 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 of IV granisetron also gave identical results when each was combined with dexamethasone. Multicenter trials have also shown the equivalence of 1 mg and 3 mg doses of granisetron.

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

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

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

Dr. Kris reiterated that this is meant to be used as prophylaxis for all patients receiving high-dose cisplatin(Drug information on cisplatin) or cyclophosphamide(Drug information on cyclophosphamide). "It is not for people who fail antiemetic therapy," he said.

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

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

With low-level chemotherapy-induced nausea and vomiting, the treatment of 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 nausea and vomiting, no initial treatment is recommended.