Annals of Oncology Advance Access published online on November 3, 2009
Annals of Oncology, doi:10.1093/annonc/mdp509
Incidence and evolution of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies
1 TGen Clinical Research Services at Scottsdale Healthcare, Scottsdale, AZ
2 Vanderbilt-Ingram Cancer Center, Nashville, TN
3 Hôpital Saint-Antoine, APHP, UPMC univ Paris 06, INSERM U8106, GERCOR, Paris, France
4 Division of Hematology–Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
5 International Clinical Development Oncology, Sanofi-aventis, Malvern, PA, USA
6 Service d'Hépato-Gastro-Entérologie, Group Hospitalier Pitié-Salpêtrière, Paris, France
* Correspondence to: Dr R. K. Ramanathan, TGen, 13208 East Shea Boulevard, Suite 100, Scottsdale, AZ 85259, USA. Tel: +1-602-358-8307; Fax: +1-602-358-8320; E-mail: rramanathan{at}tgen.org
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 
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.
colon cancer, diabetes mellitus, FOLFOX, neuropathy, oxaliplatin
Received for publication August 4, 2009. Revision received September 25, 2009. Accepted for publication September 28, 2009.