Journal
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Volume 79, Issue 3, Pages 670-676Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2009.12.007
Keywords
Rectal cancer; MRI staging; Neoadjuvant chemoradiation; Oxaliplatin; Thymidilate synthase inhibition
Funding
- Italian League for the Fight Against Cancer
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Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of <= 5 cm from the anal verge and/or with a circumferential resection margin (CRM) of <= 5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m(2); raltitrexed (RTX), 2.5 mg/m(2) on day 1, and 5-fluorouracil (5-FU), 900 mg/m(2) (31 patients) or 800 mg/m(2) (32 patients); levo-folinic acid (LFA), 250 mg/m(2) on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade >= 3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management. (C) 2011 Elsevier Inc.
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