Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term outcome

Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):670-6. doi: 10.1016/j.ijrobp.2009.12.007. Epub 2010 May 14.

Abstract

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/m2; raltitrexed (RTX), 2.5 mg/m2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m2 (31 patients) or 800 mg/m2 (32 patients); levo-folinic acid (LFA), 250 mg/m2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Diarrhea / etiology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Staging
  • Neutropenia / etiology
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Postoperative Complications / pathology
  • Preoperative Care / methods
  • Prognosis
  • Quinazolines / administration & dosage
  • Radiotherapy Dosage
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / enzymology
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery
  • Remission Induction / methods
  • Thiophenes / administration & dosage
  • Thymidylate Synthase / antagonists & inhibitors*
  • Treatment Outcome
  • Vitamin B Complex / administration & dosage

Substances

  • Neoplasm Proteins
  • Organoplatinum Compounds
  • Quinazolines
  • Thiophenes
  • Oxaliplatin
  • Vitamin B Complex
  • Thymidylate Synthase
  • raltitrexed
  • Leucovorin
  • Fluorouracil