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Title: Oxaliplatin Plus Dual Inhibition of Thymidilate Synthase During Preoperative Pelvic Radiotherapy for Locally Advanced Rectal Carcinoma: Long-Term Outcome

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{sup 2}; raltitrexed (RTX), 2.5 mg/m{sup 2} on day 1, and 5-fluorouracil (5-FU), 900 mg/m{sup 2} (31 patients) or 800 mg/m{sup 2} (32 patients); levo-folinic acid (LFA), 250 mg/m{sup 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%)more » 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.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [3] ;  [5] ;  [2] ;  [3] ;  [1] ;  [3] ;  [1] ;  [2] ;  [1] ;  [6] ;  [1]
  1. Department of Gastrointestinal Medical Oncology, National Cancer Institute, Naples (Italy)
  2. Department of Surgery Oncology, National Cancer Institute, Naples (Italy)
  3. Department of Diagnostic Imaging and Radiotherapy, National Cancer Institute, Naples (Italy)
  4. Department of Pathology, National Cancer Institute, Naples (Italy)
  5. Department of Pathology, St. James University Hospital, Leeds (United Kingdom)
  6. Department of Experimental Pharmacology, National Cancer Institute, Naples (Italy)
Publication Date:
OSTI Identifier:
21491605
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 79; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2009.12.007; PII: S0360-3016(09)03616-5; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTINEOPLASTIC DRUGS; CARCINOMAS; CHEMOTHERAPY; DIARRHEA; INHIBITION; NMR IMAGING; PELVIS; RADIOTHERAPY; RECTUM; URACILS AZINES; BODY; DIAGNOSTIC TECHNIQUES; DIGESTIVE SYSTEM; DISEASES; DRUGS; GASTROINTESTINAL TRACT; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; INTESTINES; LARGE INTESTINE; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PYRIMIDINES; RADIOLOGY; SYMPTOMS; THERAPY