Palonosetron Used With Dexamethasone Is Effective At Preventing Nausea And Vomiting After Chemotherapy

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 08 Jan 2009 - 5:00 PDT

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Palonosetron is as effective as, and in some ways better than, granisetron in preventing the nausea and vomiting that is often experienced after highly emetogenic chemotherapy, conclude the authors of a phase III comparator trial that is published in an Article Online first and in the February edition of The Lancet Oncology.

Palonosetron, a second-generation antagonist of the 5-hydroxytraptamine 3 (5-HT3) receptor, was not inferior to granisetron in preventing nausea and vomiting in the acute phase-ie, within 24 h of the start of chemotherapy. During the delayed phase-ie, 24-120 h after the initiation of anti-cancer treatment-it was better than granisetron, a first generation 5-HT3-receptor antagonist. Both drugs had a comparable safety profile.

Nausea and vomiting are traumatic side-effects that occur immediately after chemotherapy, particularly with highly emetogenic regimens containing either cisplatin or a combination of anthracycline and cyclophosphamide. Granisetron and other first generation 5-HT3-receptor antagonists can prevent emetic episodes in 50% of patients, but half still continue to experience these unpleasant side-effects. Standard treatment currently includes a first generation 5-HT3-receptor antagonist given prophylactically with dexamethasone, since this combination therapy produces a slightly higher response rate.

Phase II studies in Japan have previously demonstrated that palonosetron given with dexamethasone can prevent chemotherapy-induced nausea and vomiting effectively. Dr Mitsue Saito and colleagues have now done a phase III trial in 1143 patients receiving highly emetogenic chemotherapy to assess its efficacy and safety in combination with dexamethasone. They compared its capacity to eliminate chemotherapy-induced nausea and vomiting in a direct comparison with the granisetron/dexamethasone combination that is the current clinical standard in Japan.

Saito and colleagues found that 75•3% of patients in the palonosetron group had a complete response during the acute phase compared with 73•3% of patients in the granisetron group. The difference between the two groups showed that palonosetron is non-inferior to granisetron. In the delayed phase, 56•8% of patients in the palonosetron group had a complete response compared with 44•5% of patients in the granisetron group, indicating that palonosetron was better than the standard treatment.

The trial results confirm that palonosetron given prophylactically with dexamethasone seems to be a safe and more effective preventive treatment for the nausea and vomiting that commonly follows highly emetogenic chemotherapy. "Palonosetron might also become the primary 5-HT3-receptor antagonist to be included in the three-drug antiemetic regimen of a 5-HT3-receptor antagonist, dexamethasone, and a NK-1 antagonist, if NK-1 antagonists are introduced in Japan", says Dr Saito.

For full Article see: http://press.thelancet.com/TLOpalonosetron.pdf

Notes

- This clinical trial was a phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group active-comparator trial between palonosetron and granisetron.

- The dose of granisetron (40 µg/kg) is the approved clinical dose of this drug in Japan. The dose of palonosetron (0•75 mg) was chosen on the basis of results obtained in dose-determining phase II trials. The dose of dexamethasone was chosen according to current guidelines and to the Japanese clinical practice.

- Of the 1114 patients in the trial, 555 were assigned to the palonosetron group and 559 patients were assigned to the granisetron group. - The study protocol predefined the non-inferiority margin as a 10% difference between groups in the proportion of patients with a complete response.

Source
Tony Kirby
Press Officer
The Lancet
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