title: Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma.
abstract: BACKGROUND
  Patients with severe depletion of skeletal muscle (sarcopenia) are prone to dose-limiting toxicity (DLT) during fluoropyrimidine therapy. We hypothesized that sarcopenia may also predict toxicity of targeted therapy drugs.
  
  
  METHODS
  Metastatic renal cell cancer (RCC) patients (n = 55) received sorafenib 400 mg b.i.d. Weight, height and skeletal muscle cross-sectional area at the third lumbar vertebra were measured by computed tomography (CT). Toxicity was assessed.
  
  
  RESULTS
  DLT occurred in 22% of patients overall, of which three-quarters were dose reductions to 400 mg and the remainder entailed termination of treatment. DLT was most common (41%) in sarcopenic patients whose body mass index (BMI) was <25 kg/m(2) and least common (13%) in patients who were not sarcopenic and/or overweight or obese (P = 0.03). Toxicity was especially prevalent in sarcopenic male patients with BMI < 25, with 71% of men with these characteristics being unable to continue treatment at 800 mg/day. By contrast, only 5% of male patients whose muscle index was above the cut-off for sarcopenia and only 11% of male patients whose BMI was >25 experienced a DLT.
  
  
  CONCLUSIONS
  BMI < 25 kg/m(2) with diminished muscle mass is a significant predictor of toxicity in metastatic RCC patients treated with sorafenib.
authors.affiliation: Department of Supportive Care, Institut Gustave Roussy, Villejuif, France. Electronic address: sami.antoun@igr.fr.
authors.forename: S
authors.initials: S
authors.lastname: Antoun
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: V E
authors.initials: VE
authors.lastname: Baracos
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Birdsell
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: M B
authors.initials: MB
authors.lastname: Sawyer
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity*; D001557:Benzenesulfonates / Q000633:toxicity*; D015992:Body Mass Index; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000633:toxicity*; D055948:Sarcopenia / Q000139:chemically induced*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib