Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer.

Abstract

PURPOSE:

To evaluate neoadjuvant capecitabine/oxaliplatin before chemoradiotherapy (CRT) and total mesorectal excision (TME) in newly diagnosed patients with magnetic resonance imaging (MRI) -defined poor-risk rectal cancer.

PATIENTS AND METHODS:

MRI criteria for poor-risk rectal cancer were tumors within 1 mm of mesorectal fascia (ie, circumferential resection margin threatened), T3 tumors at or below levators, tumors extending > or = 5 mm into perirectal fat, T4 tumors, and T1-4N2 tumors. Patients received 12 weeks of neoadjuvant capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy. TME was planned 6 weeks after CRT. Postoperatively, patients received another 12 weeks of capecitabine.

RESULTS:

Between November 2001 and August 2004, 77 eligible patients were recruited. After neoadjuvant capecitabine/oxaliplatin, the radiologic response rate was 88%. In addition, 86% of patients had symptomatic responses in a median of 32 days (ie, just over one cycle of capecitabine/oxaliplatin). After CRT, the tumor response rate was increased to 97%. Three patients remained inoperable. Sixty-seven patients proceeded to TME, and all but one patient had R0 resection. Pathologic complete response was observed in 16 patients (24%; 95% CI, 14% to 36%), and in an additional 32 patients (48%), only microscopic tumor foci were found on surgical specimens. Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a result of pulmonary embolism, ischemic heart disease, sudden death with history of chest pain, and neutropenic colitis.

CONCLUSION:

Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression, rapid symptomatic response, and achievement of R0 resection.

• Authors: Ian Chau, Gina Brown, David Cunningham, Diana Tait, Andrew Wotherspoon, Andrew R Norman, Niall Tebbutt, Mark Hill, Paul J Ross, Alison Massey, Jacqueline Oates
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 4 Pg. 668-74 (Feb 01 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16446339 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Capecitabine
• Chemotherapy, Adjuvant (adverse effects)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Female
• Fluorouracil (analogs & derivatives)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neoadjuvant Therapy (adverse effects, methods)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Radiotherapy, Adjuvant (adverse effects)
• Rectal Neoplasms (drug therapy, pathology, radiotherapy, surgery, therapy)
• Risk Assessment
• Survival Analysis
• Treatment Outcome