Phase I/II Study of Preoperative Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy in Patients With Locally Advanced Rectal Cancer: Cancer and Leukemia Group B 89901
- 1 June 2006
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 24 (16), 2557-2562
- https://doi.org/10.1200/jco.2006.05.6754
Abstract
Purpose: The addition of oxaliplatin to fluorouracil in patients with advanced colorectal cancer improves survival. This phase I/II study evaluated the addition of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and external-beam radiation therapy (RT) in patients with locally advanced rectal adenocarcinoma. Patients and Methods: Patients with clinical T3/T4 rectal adenocarcinoma and no evidence of metastases were treated with weekly oxaliplatin, continuous infusion FU 200 mg/m2 intravenously, and RT. A total of 6 weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60 mg/m2. Results: Forty-four patients were entered onto the study, 18 on the phase I portion and 26 on the phase II portion. The maximum-tolerated dose (MTD) for oxaliplatin was determined to be 60 mg/m2. At the MTD, 12 patients experienced grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32 patients enrolled at the phase II dose experienced a pathologic complete response. Conclusion: In this multicenter study, the addition of oxaliplatin to intravenous continuous infusion FU and RT for patients with locally advanced rectal cancer was associated with a high pathologic complete response rate but more toxicity than when FU is used alone. A regimen of weekly oxaliplatin, continuous infusion FU, and radiation therapy is now being evaluated by the National Surgical Adjuvant Breast and Bowel Project.Keywords
This publication has 21 references indexed in Scilit:
- Preoperative versus Postoperative Chemoradiotherapy for Rectal CancerThe New England Journal of Medicine, 2004
- Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon CancerThe New England Journal of Medicine, 2004
- Impact of T and N Stage and Treatment on Survival and Relapse in Adjuvant Rectal CancerJournal of Clinical Oncology, 2004
- Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance: Report of the 22921 randomised trial conducted by the EORTC Radiotherapy GroupEuropean Journal of Cancer, 2004
- A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal CancerJournal of Clinical Oncology, 2004
- Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal CancerJournal of Clinical Oncology, 2003
- Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal CancerThe New England Journal of Medicine, 2001
- A phase I study of weekly oxaliplatin (OXA), 5-fluorouracil (5-FU) continuous infusion and preoperative radiotherapy in locally advanced rectal cancerEuropean Journal of Cancer, 2001
- Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancerInternational Journal of Radiation Oncology*Biology*Physics, 1997
- Preoperative Radiation and Chemotherapy in the Treatment of Adenocarcinoma of the RectumAnnals of Surgery, 1995