Takako Yanai1, Satoru Iwasa2, Hironobu Hashimoto1, Fumiyoshi Ohyanagi3, Tomomi Takiguchi4, Koji Takeda5, Masahiko Nakao6, Hiroshi Sakai7, Toshiaki Nakayama8, Koichi Minato9, Takahiro Arai10, Kenichi Suzuki4, Yasuhiro Shimada11, Kengo Nagashima12, Hiroyuki Terakado1, Noboru Yamamoto13. 1. Department of Pharmacy, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 2. Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 3. Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. 4. Department of Pharmacy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. 5. Department of Medical Oncology, Osaka City General Hospital, 2-13-22, Miyakojimahondohri, Miyakojima-ku, Osaka, 534-0021, Japan. 6. Department of Pharmacy, Osaka City General Hospital, 2-13-22, Miyakojimahondohri, Miyakojima-ku, Osaka, 534-0021, Japan. 7. Division of Thoracic Oncology, Saitama Cancer Center, 780, Komuro, Ina, Kitaadachi, Saitama, 362-0806, Japan. 8. Division of Pharmacy, Saitama Cancer Center, 780, Komuro, Ina, Kitaadachi, Saitama, 362-0806, Japan. 9. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, 617-1 Takahayashi-nishi-cho, Ohta, Gunma, 373-0828, Japan. 10. Division of Pharmacy, Gunma Prefectural Cancer Center, 617-1 Takahayashi-nishi-cho, Ohta, Gunma, 373-0828, Japan. 11. Clinical Oncology Division, Kochi Health Sciences Center, 2125-1, Ike, Kochi, Kochi, 781-8555, Japan. 12. Department of Global Clinical Research, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-8670, Japan. 13. Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nbryamam@ncc.go.jp.
Abstract
PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). METHODS: A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receivingHEC with cisplatin (≥ 50 mg/m2). Patients were randomly assigned either olanzapine 10 or 5 mg orally on days 1-4, combined with standard antiemetic treatment. The primary endpoint was a complete response (CR; no emesis and no use of rescue medications) in the delayed phase (24-120 h after the start of cisplatin treatment). RESULTS:153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H 0: complete response rate ≤ 65%). The most common adverse event was somnolence, which had an incidence of 53.3 and 45.5% in the 10 and 5 mg olanzapine groups, respectively. CONCLUSIONS: Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates. CLINICAL TRIAL INFORMATION: UMIN000014214.
RCT Entities:
PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). METHODS: A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m2). Patients were randomly assigned either olanzapine 10 or 5 mg orally on days 1-4, combined with standard antiemetic treatment. The primary endpoint was a complete response (CR; no emesis and no use of rescue medications) in the delayed phase (24-120 h after the start of cisplatin treatment). RESULTS: 153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H 0: complete response rate ≤ 65%). The most common adverse event was somnolence, which had an incidence of 53.3 and 45.5% in the 10 and 5 mg olanzapine groups, respectively. CONCLUSIONS: Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates. CLINICAL TRIAL INFORMATION: UMIN000014214.
Entities:
Keywords:
Chemotherapy-induced nausea and vomiting; Olanzapine; Phase II study; Prophylaxis
Authors: F P Bymaster; D L Nelson; N W DeLapp; J F Falcone; K Eckols; L L Truex; M M Foreman; V L Lucaites; D O Calligaro Journal: Schizophr Res Date: 1999-05-04 Impact factor: 4.939
Authors: A Schotte; P F Janssen; W Gommeren; W H Luyten; P Van Gompel; A S Lesage; K De Loore; J E Leysen Journal: Psychopharmacology (Berl) Date: 1996-03 Impact factor: 4.530
Authors: K Suzuki; T Yamanaka; H Hashimoto; Y Shimada; K Arata; R Matsui; K Goto; T Takiguchi; F Ohyanagi; Y Kogure; N Nogami; M Nakao; K Takeda; K Azuma; S Nagase; T Hayashi; K Fujiwara; T Shimada; N Seki; N Yamamoto Journal: Ann Oncol Date: 2016-06-29 Impact factor: 32.976
Authors: Ethan Basch; Ann Alexis Prestrud; Paul J Hesketh; Mark G Kris; Petra C Feyer; Mark R Somerfield; Maurice Chesney; Rebecca Anne Clark-Snow; Anne Marie Flaherty; Barbara Freundlich; Gary Morrow; Kamakshi V Rao; Rowena N Schwartz; Gary H Lyman Journal: J Clin Oncol Date: 2011-09-26 Impact factor: 44.544
Authors: Rudolph M Navari; Rui Qin; Kathryn J Ruddy; Heshan Liu; Steven F Powell; Madhuri Bajaj; Leah Dietrich; David Biggs; Jacqueline M Lafky; Charles L Loprinzi Journal: N Engl J Med Date: 2016-07-14 Impact factor: 91.245
Authors: Steven D Passik; Rudolph M Navari; Sin-Ho Jung; Cindy Nagy; Jake Vinson; Kenneth L Kirsh; Patrick Loehrer Journal: Cancer Invest Date: 2004 Impact factor: 2.176
Authors: Rudolph M Navari; Lawrence H Einhorn; Steven D Passik; Patrick J Loehrer; Cynthia Johnson; M L Mayer; J McClean; Jake Vinson; W Pletcher Journal: Support Care Cancer Date: 2005-02-08 Impact factor: 3.603
Authors: Anil R Maharaj; Huali Wu; Kanecia O Zimmerman; Julie Autmizguine; Rohit Kalra; Amira Al-Uzri; Catherine M T Sherwin; Stuart L Goldstein; Kevin Watt; Jinson Erinjeri; Elizabeth H Payne; Michael Cohen-Wolkowiez; Christoph P Hornik Journal: Br J Clin Pharmacol Date: 2020-07-05 Impact factor: 3.716