Phase I/II trial of 2‐weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807) |
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| Authors: | Shuichi Hironaka Yasuhiro Tsubosa Junki Mizusawa Takayuki Kii Ken Kato Takahiro Tsushima Keisho Chin Akihisa Tomori Tatsuya Okuno Toshikatsu Taniki Takashi Ura Hisayuki Matsushita Takashi Kojima Yuichiro Doki Hitoshi Kusaba Kazumasa Fujitani Koichi Taira Shiko Seki Tsutomu Nakamura Yuko Kitagawa Japan Esophageal Oncology Group/Japan Clinical Oncology Group |
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| Affiliation: | 1. Clinical Trial Promotion Department, Chiba Cancer Center, , Chiba, Japan;2. Division of esophageal surgery, Shizuoka Cancer Center, , Shizuoka, Japan;3. JCOG Data Center, Multi‐institutional Clinical Trial Support Center, National Cancer Center, , Tokyo, Japan;4. Cancer Chemotherapy Center, Osaka Medical College, , Osaka, Japan;5. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, , Tokyo, Japan;6. Department of Gastroenterology, Cancer Institute Hospital, , Tokyo, Japan;7. Department of Gastroenterology, Saku Central Hospital, , Nagano, Japan;8. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, , Kobe, Japan;9. Department of gastroenterological and general surgery, Kochi Health Sciences Center, , Kochi, Japan;10. Department of Clinical Oncology, Aichi Cancer Center, , Nagoya, Japan;11. Department of Surgery, Tochigi Cancer Center, , Utsunomiya, Japan;12. Gastrointestinal Oncology Division, National Cancer Center Hospital East, , Kashiwa, Japan;13. Gastroenterological Surgery, Osaka University, , Osaka, Japan;14. Department of Medicine and Biosystemic Science, Kyushu University, , Fukuoka, Japan;15. Department of Surgery, Osaka National Hospital, , Osaka, Japan;16. Division of Clinical Oncology, Osaka City General Hospital, , Osaka, Japan;17. Department of Surgery, National Hospital Organization Tokyo Medical Center, , Tokyo, Japan;18. Department of Gastroenterological Surgery, Tokyo Women's Medical University, , Tokyo, Japan;19. Department of Surgery, Keio University School of Medicine, , Tokyo, Japan |
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| Abstract: | We carried out a phase I/II trial of adding 2‐weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2‐weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2‐weekly docetaxel (30 mg/m2 [dose level (DL)1] or 40 mg/m2 [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed‐dose CF (80 mg/m2 cisplatin, day 1; 800 mg/m2 fluorouracil, days 1–5) repeated every 4 weeks. The primary endpoint was dose‐limiting toxicity (DLT) in phase I and central peer review‐based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty‐two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48–75%); median overall survival and progression‐free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment‐related death in one patient. The 2‐weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737. |
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| Keywords: | Chemotherapy DCF therapy metastatic esophageal cancer phase I/II 2‐weekly docetaxel |
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