Incidence and evolution of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies

Ann Oncol. 2010 Apr;21(4):754-758. doi: 10.1093/annonc/mdp509. Epub 2009 Nov 3.

Abstract

Background: The purpose of this study was to determine whether the presence of diabetes mellitus (DM) influences the incidence, severity, and/or course of peripheral sensory neuropathy (PSN) after oxaliplatin (FOLFOX) therapy in patients with colorectal cancer (CRC).

Methods: A retrospective pooled analysis incorporating three phase III studies was conducted: Multicenter International Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) (adjuvant treatment; stage II/III colon cancer), EFC4584 (second-line treatment; metastatic CRC), and EFC2962 (first-line treatment; metastatic CRC). Patients were ineligible for the studies if they had known PSN (EFC4584) or PSN grade > or =1 (MOSAIC and EFC2962) at baseline. The incidence of PSN was evaluated retrospectively in patient subgroups with or without DM at baseline that received FOLFOX. Kaplan-Meier curves were used to assess the probability of PSN with increasing cumulative oxaliplatin dose.

Results: Of 1587 patients enrolled across the three studies, 135 (8.5%) had DM at baseline. The incidence of PSN (non-DM/DM) was 45.0%/46.7% (grade 1), 28.6%/26.7% (grade 2), and 13.0%/12.6% (grade 3). The probability of PSN by cumulative dose of oxaliplatin was similar in DM and non-DM patients.

Conclusions: This retrospective analysis indicates that oxaliplatin-based therapy does not influence the incidence, severity, or time to onset of PSN in asymptomatic DM patients with CRC who meet eligibility criteria for clinical trials.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Carcinoma / complications
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Diabetes Complications / chemically induced
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / pathology
  • Diabetic Neuropathies / chemically induced*
  • Diabetic Neuropathies / epidemiology*
  • Diabetic Neuropathies / pathology
  • Disease Progression
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Organoplatinum Compounds / adverse effects*
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Retrospective Studies
  • Sensory Receptor Cells / pathology

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin