Japanese Journal of Clinical Oncology Advance Access originally published online on July 19, 2006
Japanese Journal of Clinical Oncology 2006 36(8):504-510; doi:10.1093/jjco/hyl064
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© 2006 Foundation for Promotion of Cancer Research
Phase I/II Trial of Hyperfractionated Accelerated Chemoradiotherapy for Unresectable Advanced Pancreatic Cancer
1 Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, 2 Department of Radiology, Graduate School of Medicine, Osaka University, Suita, Osaka, 3 Department of Multidisciplinary Radiotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, 4 Department of Surgery, Cancer Center, Department of Molecular Medicine, Osaka National Hospital, National Hospital Organization, Osaka and 5 Department of Radiotherapy, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
For reprints and all correspondence: Shoji Nakamori, Chief Surgeon of Department of Surgery, Cancer Center, Head of Department of Molecular Medicine, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan. E-mail: nakamori{at}onh.go.jp
Received February 16, 2006; accepted May 8, 2006
Background: We conducted a Phase I/II study to evaluate the local efficacy and toxicity of hyperfractionated accelerated radiotherapy (HART) combined with 5-fluorouracil (5-FU) and cisplatin (CDDP) in patients with unresectable advanced pancreatic cancer.
Methods: Thirty-five patients (15 with Stage 4A and 20 with Stage 4B disease according to TNM classification) were enrolled between August 1997 and August 2001 into this Phase I/II trial. All patients received concurrent HART (1.5 Gy twice daily separated by 6 h for 5 days per week), 5-FU (375 mg/m2 given as continuous intravenous infusion), and CDDP (2 mg/m2 given as 30-min infusion just before each fraction of irradiation). In the Phase I trial, the total dose of radiation was escalated from 27 to 45 Gy.
Results: Twenty-one patients were enrolled in the Phase I study and six patients were given the final planned dose (45 Gy) which did not exceed the maximum tolerated dose. Eleven patients (52.4%) suffered from Grade 3 or worse neutropenia. Vomiting and mucositis were observed in 21 (100%) and 12 (57.1%) patients, respectively. An additional 14 patients were entered in the Phase II trial and received a total dose of 45 Gy, which is recommended in Phase I trial. Concerning the local tumor control of 20 patients with the recommended regimen, 7 patients (35%) achieved partial response, 10 (50%) remained stable and local progressive disease occurred in 3 (15%). The median survival time and the overall 1-year survival rate were 11.2 months and 40.0%, respectively, in 20 patients who received the recommended regimen. In Stage 4A patients, they were 13.0 months and 70.0%, respectively. The trend of toxicities in patients with the recommended regimen was almost the same as that observed in the Phase I study.
Conclusion: The chosen combined modality treatment was well tolerated, and showed an expected local efficacy for the treatment of unresectable advanced pancreatic cancer.
Key Words: pancreatic cancer • radiotherapy • chemotherapy • 5-fluorouracil • cisplatin