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NK1 Receptor Boosts Benefits of Standard Antiemetic Therapy

NK1 Receptor Boosts Benefits of Standard Antiemetic Therapy

ORLANDO—When combined with standard antiemetic therapy, the
neurokinin-1 (NK1) receptor antagonist aprepitant (MK-869[M]) protects
against acute and delayed chemotherapy-induced nausea and vomiting,
according to two separate studies (ASCO abstracts 1467 and 1467).

"We have been working with NK1 antagonists for over a decade, but
until now, there really were no new agents.

Now we have a once-daily oral agent that adds to existing
medications," Ronald de Wit, MD, PhD, told Oncology News
He is director of the inpatient department of medical oncology at Rotterdam
Cancer Institute and Erasmus Medical Center of University Hospital in
Rotterdam, the Netherlands. "In phase III clinical studies, aprepitant
added 10% to 15% to emesis relief in the early phase and about 25% in the
later phase, at days 2 to 5 after the start of chemotherapy," Dr. de
Wit explained.

Before Cisplatin Therapy

Before receiving their first dose of a chemotherapy regimen including
cisplatin (Platinol) greater than 70 mg/m², 202 patients between ages 20 and
82 were randomized to one of three treatment groups. Group I received
aprepitant, 375 mg on day 1 and 250 mg on days 2 to 5. Group II received
aprepitant, 125 mg on day 1 and 80 mg on days 2 to 5. Group III received
placebo on days 1 to 5.

All patients received standard antiemetic therapy with intravenous
ondansetron (Zofran) at 32 mg, and oral dexamethasone (Decadron) at 20 mg,
before receiving cisplatin on day 1, and dexamethasone on days 2 to 5.
Because of pharmacokinetic data from healthy volunteers, the group I regimen
was discontinued, and efficacy evaluations were based on only groups II and

Compared with standard therapy alone, triple combination therapy
including aprepitant provided 34% better protection against
chemotherapy-induced nausea and vomiting throughout multiple chemotherapy
cycles. Although standard therapy decreased in efficacy after three cycles,
the triple combination regimen maintained efficacy during all six cycles.


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