1. Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas
- Author
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Joerg Rathmann, Raul Vera-Gimon, Richard J. Barth, Raymond P. Perez, Thomas A. Colacchio, Lionel D. Lewis, J. Marc Pipas, Carol E. McDonnell, Louise P. Meyer, Richard S Wagman, and Sandra E. Mitchell
- Subjects
Adult ,Male ,Antimetabolites, Antineoplastic ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,Adenocarcinoma ,Deoxycytidine ,Disease-Free Survival ,Drug Administration Schedule ,Radiotherapy, High-Energy ,Pancreatectomy ,Pancreatic cancer ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,External beam radiotherapy ,Bone Marrow Diseases ,Fatigue ,Chemotherapy ,Radiation ,business.industry ,Radiotherapy Planning, Computer-Assisted ,Remission Induction ,Nausea ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Gemcitabine ,Surgery ,Pancreatic Neoplasms ,Radiation therapy ,Regimen ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,Concomitant ,Female ,Gastrointestinal Hemorrhage ,business ,Follow-Up Studies ,medicine.drug - Abstract
Purpose: To determine the maximum tolerated dose and dose-limiting toxicity associated with twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas. Methods and Materials: Twenty-one patients with biopsy-proven adenocarcinoma of the pancreas were treated with external-beam radiotherapy to a dose of 50.4 Gy in 28 fractions, concurrent with gemcitabine, infused over 30 min before irradiation on a Monday and Thursday schedule. The dose of gemcitabine was escalated in 5 cohorts of 3–6 patients each. Initial gemcitabine dose was 10 mg/m 2 , with dose escalation until dose-limiting toxicity was observed. Results: The maximum tolerated dose of gemcitabine was 50 mg/m 2 , when given in a twice-weekly schedule with radiation. Dose-limiting toxicity was seen in 2 patients at 60 mg/m 2 , and consisted of severe upper gastrointestinal bleeding approximately 1 month after completion of treatment. Six patients had radiographic evidence of response to treatment, and 5 of these underwent complete surgical resection. Three patients who underwent complete resection had been deemed to have unresectable tumors before enrollment on trial. Four patients are alive, including 2 without evidence of disease more than 1 year after resection. Conclusion: The combination of external-beam radiation and twice-weekly gemcitabine at a dose of 50 mg/m 2 is well tolerated and shows promising activity for the treatment of pancreatic cancer. Our data suggest a higher maximum tolerated dose and different dose-limiting toxicity than previously reported. Further investigation of this regimen is warranted.
- Published
- 2001