PALO vs GRA for preventing CINV in HEC: A randomized, double-blind, phaseIII trial
演題番号 : PS2-5
1:National Hospital Organization Shikoku Cancer Center, Japan、2:National Cancer Center Hospital, Japan、3:National Kyushu Cancer Center, Japan、4:Kouseiren Takaoka Hospital, Japan、5:Saitama Medical Center, Saitama Medical Univ., Japan、6:Aichi Cancercenter Hospital, Japan、7:Tochigi Cancer Center, Japan、8:Research Center for Innovative Oncology, National Cancer Center Hospital East, Japan、9:Shizuoka Cancer Center, Japan、10:The Cancer Institute Hospital of JAPANESE FOUNDATION FOR CANCER RESEARCH, Japan
Standard antiemetic care for preventing chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC) is a combination of 5-HT3 receptor antagonist (RA), dexamethasone (DEX), and aprepitant (APR). This study compared the efficacy of two 5-HT3 RAs, palonosetron (PALO) and granisetron (GRA), in the triplet regimen.
Patients with a malignant solid tumor who were receiving HEC containing 50 mg/m2 or more cisplatin (CDDP) were enrolled. They were randomly assigned to either Arm A (PALO 0.75 mg, i.v.) or Arm B (GRA 1 mg, i.v.), 30 min before chemotherapy on day 1, both arms with DEX (9.9 mg on day 1 and 6.6 mg on days 2-4, i.v.) and APR (125 mg on day 1 and 80 mg on days 2-3, p.o.). Primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medications) in the overall (0-120 hours) phase. Secondary endpoints included CR in the acute (0-24 h) and delayed (24-120 h) phases, complete control (CC; no emetic episodes and no more than mild nausea) and total control (TC; no emetic episodes, no rescue medications, and no nausea). The planned sample size of 840 provided 90% power to detect a 10% improvement in the CR at 0-120 h with two-sided alpha of 0.05. Primary analysis was conducted with exact Cochran-Mantel-Haenszel (CMH) test.
Between July 2011 and June 2012, 842 patients were enrolled and 827 were evaluable. The median CDDP dose was 76.1 mg/m2 in Arm A and 75.7 mg/m2 in Arm B. Baseline factors were well-balanced. The overall CR rates were 66% in Arm A and 59% in Arm B (P=0.0539). In the delayed phase, Arm A exerted a significantly higher CR rate than Arm B (67% vs. 59%; P=0.0142). The overall TC rates were 48% in Arm A and 41% in Arm B(P=0.0369).
Primary endpoint was not met. However, the overall study results have shown the clinical utility of PALO in the triplet regimen. PALO is a more preferable 5-HT3 RA in the triplet regimen than GRA for preventing CINV due to HEC.