Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07

Stephanie R. Land*, Jacek A. Kopec, Reena S. Cecchini, Patricia A. Ganz, H. Samuel Wieand, Linda H. Colangelo, Kate Murphy, J. Philip Kuebler, Thomas E. Seay, Burton M. Needles, James D. Bearden, Lauren K. Colman, Keith S. Lanier, Eduardo R. Pajon, David Cella, Roy E. Smith, Michael J. O'Connell, Joseph P. Costantino, Norman Wolmark

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

Purpose: The randomized, multicenter, phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin (FULV) versus FULV with oxaliplatin (FLOX) in stage II or III colon cancer. Definitive analysis revealed an increase in 4-year disease-free survival from 67.0% to 73.2% in favor of FLOX. This study compares neurotoxicity between the treatments. Patients and Methods: Neurotoxicity was recorded for all patients using standard adverse event reporting. Patients at select institutions completed a neurotoxicity questionnaire through 18 months of follow-up. Results: A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported substudy. Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study (P < .0001). During therapy, patients receiving oxaliplatin experienced significantly more hand/foot toxicity (eg, "quite a bit" of cold-induced hand/foot pain 26% FLOX v/2.6% FULV) and overall weakness (eg, moderate weakness in 27.4% FLOX v 16.2% FULV). At 18 months, hand neuropathy had diminished, but patients who received oxaliplatin experienced continued foot discomfort (eg, moderate foot numbness and tingling for 22.1% FLOX v 4.6% FULV). Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor. Sixty-eight percent in the FLOX group v 8% in the FULV group had neurotoxicity at their first on-treatment assessment. Time to resolution was significantly longer for those receiving oxaliplatin, and continued beyond 2 years for more than 10% in the oxaliplatin group. Conclusion: Oxaliplatin causes significant neurotoxicity. It is experienced primarily in the hands during therapy and in the feet during follow-up. In a minority of patients the neurotoxicity is long lasting.

Original languageEnglish (US)
Pages (from-to)2205-2211
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number16
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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