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.
Dr Mitsue Saito Department of Breast Oncology, Juntendo University Hospital, Tokyo, Japan Email: mitsue@juntendo.ac.jp Tel: + 81-3-3813-3111 (EXT 5855 or 3396)
For full Article see: http://press.thelancet.com/TLOpalonosetron.pdf
Notes for editors
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.
Journal
The Lancet Oncology