Palonosetron Superior to Granisetron in Preventing Chemotherapy-Induced Emesis

Roxanne Nelson

September 14, 2008

September 14, 2008 (Stockholm, Sweden) — Emesis can be a significant consequence of cytotoxic chemotherapy and radiotherapy, and can drastically affect the quality of life of patients undergoing these therapies. The 5-HT3 receptor antagonists have been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV), and now 1 of the newest agents in this field, palonosetron (Aloxi, Onicil, Paloxi), marketed by Helsinn Healthcare, has shown superior efficacy to a second-generation agent, granisetron (Kytril, Roche).

Japanese researchers reported here at the 33rd European Society for Medical Oncology Congress that palonosetron was superior to granisetron in preventing delayed-phase CINV. It was also more effective in inducing an overall complete response rate in the study cohort. However, both agents demonstrated similar efficacy in preventing acute-phase CINV.

"This is a first step in Japan," said lead author Hirohisa Yoshizawa, MD, from the Niigata University Medical and Dental Hospital, Bioscience Research Center, in Japan. "Palonosetron has been approved in the US and Europe but not in Japan. We are hoping that our results will lead to approval."

Palonosetron is a highly selective second-generation 5-HT3 receptor antagonist that has demonstrated efficacy and long-lasting protection from CINV. It has a higher binding affinity and longer half-life than other 5-HT3 receptor antagonists, and in the United States has been approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy.

"Patients only need 1 dose of palonosetron, so it may be very cost effective as well," Dr. Yoshizawa told Medscape Oncology.

In this study, Dr. Yoshizawa and colleagues from the PALO Japanese Cooperative Study Group compared the efficacy of single-dose IV palonosetron (0.75 mg) with IV granisetron (40 µg/kg) in 1114 patients who were scheduled to receive at least 50 mg/m2 of cisplatin or of epirubicin or doxorubicin plus cyclophosphamide (AC/EC). Granisetron has already been approved in Japan, and patients were randomized to receive either agent. Dexamethasone was also administered to all patients: 16 mg on day 1, and 4 mg on days 2 and 3 for patients receiving AC/EC, or 8 mg for those being treated with cisplatin.

As a secondary end point, the researchers compared the safety of palonosetron with granisetron in patients receiving highly emetogenic chemotherapy.

Overall, a complete response was seen in 51.5% of patients who received palonosetron, compared with 40.4% who received granisetron. Complete response rates were similar for acute-phase CINV (77.5% for palonosetron vs 75.2% for granisetron), but palonosetron was superior in preventing delayed-phase CINV (56.8% vs 44.5%).

"We saw a significant improvement in late emesis with palonosetron," said Dr. Yoshizawa. "This is really important for patients."

Subgroup analyses by sex, age, and chemotherapy protocol showed similar results: palonosetron was similar to granisetron in preventing acute-phase CINV but superior in eliciting an overall complete response and preventing delayed-phase CINV.

The authors also observed that significantly more patients in the palonosetron group experienced no nausea or emesis during the delayed and the overall time intervals. Time to treatment failure was also significantly longer in the palonosetron group than in the granisetron group.

The researchers concluded that palonosetron can contribute to the supportive care of patients undergoing chemotherapy, because it is more effective than other 5-HT3 receptor antagonists. Palonosetron plus dexamethasone should be the standard base antiemetic regimen for patients undergoing highly emetogenic cancer chemotherapy, they said.

33rd European Society of Medical Oncology (ESMO) Congress: Abstract 894P. Presented September 13, 2008.

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