Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma

Ann Oncol. 2010 Aug;21(8):1594-1598. doi: 10.1093/annonc/mdp605. Epub 2010 Jan 20.


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.

Materials and 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.

Conclusion: BMI < 25 kg/m(2) with diminished muscle mass is a significant predictor of toxicity in metastatic RCC patients treated with sorafenib.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / toxicity*
  • Benzenesulfonates / toxicity*
  • Body Mass Index*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / toxicity*
  • Sarcopenia / chemically induced*
  • Sorafenib


  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Sorafenib