Naohiro Okano1, Chigusa Morizane2, Shogo Nomura3, Hideaki Takahashi4, Hidetaka Tsumura5, Hironaga Satake6, Nobumasa Mizuno7, Kunihiro Tsuji8, Kazuhiko Shioji9, Akinori Asagi10, Kohichiroh Yasui11, Sho Kitagawa12, Tomomi Kashiwada13, Atsushi Ishiguro14, Masashi Kanai15, Makoto Ueno16, Takashi Ogura17, Satoshi Shimizu18, Kazutoshi Tobimatsu19, Masayo Motoya20, Koji Nakashima21, Masafumi Ikeda4, Takuji Okusaka2, Junji Furuse22. 1. Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan. naohiro-okano@ks.kyorin-u.ac.jp. 2. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. 3. Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Kashiwa, Japan. 4. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 5. Department of Gastroenterology, Hyogo Cancer Center, Hyogo, Japan. 6. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. 7. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. 8. Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan. 9. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 10. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 11. Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 12. Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, Japan. 13. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan. 14. Department of Medical Oncology, Teine Keijinkai Hospital, Sapporo, Japan. 15. Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 16. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan. 17. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. 18. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 19. Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. 20. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan. 21. Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, Japan. 22. Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers. METHODS: Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled. RESULTS: Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities. CONCLUSION: GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended. TRIAL REGISTRATION NUMBER: UMIN000017894.
BACKGROUND: A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers. METHODS: Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled. RESULTS: Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities. CONCLUSION:GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended. TRIAL REGISTRATION NUMBER: UMIN000017894.