Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer. A phase I-II multicenter study of the Dutch Colorectal Cancer Group

Ann Surg Oncol. 2007 Oct;14(10):2773-9. doi: 10.1245/s10434-007-9396-6. Epub 2007 Jul 26.

Abstract

Background: We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer.

Methods: T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m(2) twice daily (days 1-14, 25-38) added to RT with 50.4 Gy and surgery after 6-8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point.

Results: Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m(2) was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21.

Conclusion: Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / toxicity
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / toxicity
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / toxicity
  • Oxaliplatin
  • Pain Measurement
  • Particle Accelerators
  • Quality of Life
  • Radiotherapy Dosage
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery
  • Rectum / pathology
  • Rectum / surgery

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil