title: Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens.
abstract: Evidence suggests that lean body mass (LBM) may be useful to normalize chemotherapy doses. Data from one prospective and one retrospective study were used to determine if the highest doses of oxaliplatin/kg LBM within FOLFOX regimens would be associated with dose-limiting toxicity (DLT) in colon cancer patients. Toxicity over four cycles was graded according to NCI Common Toxicity Criteria V2 or V3 (Common Terminology Criteria for Adverse Events, National Cancer Institute, Bethesda, MD). Muscle tissue was measured by computerized tomography (CT) and used to evaluate the LBM compartment of the whole body. In prospective randomized clinical trials conducted in France (n = 58), for patients given FOLFOX-based regimens according to body surface area, values of oxaliplatin/kg LBM were highly variable, ranging from 2.55 to 6.6 mg/kg LBM. A cut point of 3.09 mg oxaliplatin/kg LBM for developing toxicity was determined by Receiver Operating Characteristic (ROC) analysis, below this value 0/17 (0.0%) of patients experienced DLT; in contrast above this value 18/41 (44.0%) of patients were dose reduced or had treatment terminated owing to toxicity (≥Grade 3 or neuropathy ≥Grade 2); for 9/41 the DLT was sensory neuropathy. These findings were validated in an independent cohort of colon cancer patients (n = 80) receiving FOLFOX regimens as part of standard care, in Canada. Low LBM is a significant predictor of toxicity and neuropathy in patients administered FOLFOX-based regimens using conventional body surface area (BSA) dosing.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: Raafi
authors.initials: R
authors.lastname: Ali
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: Vickie E
authors.initials: VE
authors.lastname: Baracos
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sawyer
authors.affiliation: Department of Clinical Nutrition and Gastroenterology, Institute of Cancer Montpellier, Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Department of Gastroenterology, University Hospital Montpellier France, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Assenat
authors.affiliation: Biometrics Unit - CTD INCa, Institut régional du Cancer de Montpellier (ICM), Montpellier, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mollevi
authors.affiliation: Department of Clinical Nutrition and Gastroenterology, Institute of Cancer Montpellier, Montpellier, France.|SIRIC Montpellier Cancer, Institut régional du Cancer de Montpellier (ICM), Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Senesse
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001823:Body Composition; D015992:Body Mass Index; D001830:Body Surface Area; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005602:France / Q000453:epidemiology; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000453:epidemiology / Q000209:etiology*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011159:Population Surveillance
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil
keywords: Body composition; chemotherapy toxicity; colon cancer; irinotecan; lean body mass; neuropathy; oxaliplatin
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