Akihiko Osaki1, Kenichi Inoue2, Hiroshi Sakai3, Kazuhiko Yamada4, Koichi Minato5, Fumiyoshi Ohyanagi6,7, Yutaka Tokuda8, Norihiko Ikeda9, Hiroshi Kagamu10,11, Kaoru Kubota12, Tomohide Tamura13, Toshiaki Saeki1. 1. Department of Breast Oncology, Saitama Medical University International Medical Center, Saitama. 2. Division of Breast Oncology, Saitama Cancer Center, Saitama. 3. Department of Thoracic Oncology, Saitama Cancer Center, Saitama. 4. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka. 5. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma. 6. Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo. 7. Division of Pulmonary Medicine, Clinical Department of Internal Medicine, Jichi Medical University Saitama Medical Center, Saitama. 8. Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa. 9. Department of Surgery, Tokyo Medical University, Tokyo. 10. Department of Respiratory Medicine and Infectious Disease, Niigata University Medical and Dental Hospital, Niigata. 11. Department of Respiratory Medicine, Saitama Medical University International Medical Center, Saitama. 12. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo. 13. Thoracic Center, St. Luke's International Hospital, Tokyo, Japan.
Abstract
OBJECTIVE: Netupitant is a novel, selective neurokinin-1 receptor antagonist used for prevention of chemotherapy-induced nausea and vomiting, a distressing side effect of chemotherapy. This double-blind, randomized, Phase II study investigated the dose-response of oral netupitant in Japanese patients receiving highly emetogenic chemotherapy. METHODS: Chemotherapy-naïve patients were randomized (1:1:1) to a single oral netupitant 30-, 100- or 300-mg dose before chemotherapy initiation. Patients received concomitant palonosetron (0.75 mg intravenously [i.v.] Day 1) and dexamethasone (9.9 mg i.v. Day 1, 8 mg orally Days 2-4). RESULTS: Overall, 402 patients (30 mg: 134; 100 mg: 135; 300 mg: 133) were treated and evaluable for efficacy and safety. The primary endpoint of overall (0-120 h after chemotherapy administration) complete response (CR) rate (no emesis, no rescue medication) was 64.2%, 60.0% and 54.9% in the 30-, 100- and 300-mg arms, respectively, without statistical significance for dose-response. The safety profile of netupitant was comparable in the three arms. The plasma concentrations of netupitant and its metabolites increased with the dose increase from 30 mg to 300 mg. CONCLUSIONS: No dose-response relationship of netupitant in terms of overall CR rate was observed in this study. Netupitant was well tolerated at all doses without clinically harmful safety signals observed. CLINICAL TRIAL REGISTRATION: JapicCTI-142 483.
OBJECTIVE: Netupitant is a novel, selective neurokinin-1 receptor antagonist used for prevention of chemotherapy-induced nausea and vomiting, a distressing side effect of chemotherapy. This double-blind, randomized, Phase II study investigated the dose-response of oral netupitant in Japanese patients receiving highly emetogenic chemotherapy. METHODS: Chemotherapy-naïve patients were randomized (1:1:1) to a single oral netupitant 30-, 100- or 300-mg dose before chemotherapy initiation. Patients received concomitant palonosetron (0.75 mg intravenously [i.v.] Day 1) and dexamethasone (9.9 mg i.v. Day 1, 8 mg orally Days 2-4). RESULTS: Overall, 402 patients (30 mg: 134; 100 mg: 135; 300 mg: 133) were treated and evaluable for efficacy and safety. The primary endpoint of overall (0-120 h after chemotherapy administration) complete response (CR) rate (no emesis, no rescue medication) was 64.2%, 60.0% and 54.9% in the 30-, 100- and 300-mg arms, respectively, without statistical significance for dose-response. The safety profile of netupitant was comparable in the three arms. The plasma concentrations of netupitant and its metabolites increased with the dose increase from 30 mg to 300 mg. CONCLUSIONS: No dose-response relationship of netupitant in terms of overall CR rate was observed in this study. Netupitant was well tolerated at all doses without clinically harmful safety signals observed. CLINICAL TRIAL REGISTRATION: JapicCTI-142 483.