title: Incidence and evolution of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies.
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.
authors.affiliation: TGen Clinical Research Services at Scottsdale Healthcare, Scottsdale, AZ. Electronic address: rramanathan@tgen.org.
authors.forename: R K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Vanderbilt-Ingram Cancer Center, Nashville, TN.
authors.forename: M L
authors.initials: ML
authors.lastname: Rothenberg
authors.affiliation: Hôpital Saint-Antoine, APHP, UPMC univ Paris 06, INSERM U8106, GERCOR, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: de Gramont
authors.affiliation: Hôpital Saint-Antoine, APHP, UPMC univ Paris 06, INSERM U8106, GERCOR, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Tournigand
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: R M
authors.initials: RM
authors.lastname: Goldberg
authors.affiliation: International Clinical Development Oncology, Sanofi-aventis, Malvern, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Service d'Hépato-Gastro-Entérologie, Group Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: André
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D048909:Diabetes Complications / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009944:Organoplatinum Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012189:Retrospective Studies; D011984:Sensory Receptor Cells / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin