Chizuru Sakai1, Mototsugu Shimokawa2,3, Hirotoshi Iihara4,5, Yukiyoshi Fujita6, Shinnosuke Ikemura7,8, Chiemi Hirose4, Mie Kotake9, Norihiko Funaguchi10, Takenobu Gomyo1, Hisao Imai9,11, Jun Hakamata12, Daizo Kaito1, Koichi Minato9, Takahiro Arai6, Hitoshi Kawazoe13, Akio Suzuki4,5, Yasushi Ohno1, Hiroyuki Okura1. 1. Department of Cardiology and Respiratory Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan. 2. Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. 3. Cancer Biostatistics Laboratory, Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka, Japan. 4. Department of Pharmacy, Gifu University Hospital, Gifu, Gifu, Japan. 5. Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Gifu, Japan. 6. Division of Pharmacy, Gunma Prefectural Cancer Center, Ohta, Gunma, Japan. 7. Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, Shinjuku-ku, Tokyo, Japan. 8. Keio Cancer Center, Keio University, School of Medicine, Shinjuku-ku, Tokyo, Japan. 9. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ohta, Gunma, Japan. 10. Department of Respirology, Asahi University Hospital, Gifu, Gifu, Japan. 11. Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan (present address). 12. Department of Pharmacy, Keio University Hospital, Shinjuku-ku, Tokyo, Japan. 13. Division of Pharmaceutical Care Sciences, Center for Social Pharmacy and Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
Abstract
BACKGROUND: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies. MATERIALS AND METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours). RESULTS: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. CONCLUSION: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267. IMPLICATIONS FOR PRACTICE: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.
BACKGROUND:Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies. MATERIALS AND METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours). RESULTS: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. CONCLUSION: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267. IMPLICATIONS FOR PRACTICE: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.