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.
NCCN Antiemesis Practice Guidelines Panel Members
David Ettinger, MD
Steven Huber, PharmD
Mark Kris, MD
Michael Levy, MD
Bob McNulty, PharmD
Kimberly Rogers Noonan, RN
Lisa Stucky-Marshall, RN
Susan Urba, MD
"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 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
For highly emetogenic chemotherapy regimens, the guidelines recommend
oral granisetron (Kytril) plus dexamethasone with or without 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
"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 or 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
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.