Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma.
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.
Antoun
S
S
Department of Supportive Care, Institut Gustave Roussy, Villejuif, France. Electronic address: sami.antoun@igr.fr.
Baracos
V E
VE
Department of Oncology, University of Alberta, Edmonton, Canada.
Birdsell
L
L
Department of Oncology, University of Alberta, Edmonton, Canada.
Escudier
B
B
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
Sawyer
M B
MB
Department of Oncology, University of Alberta, Edmonton, Canada.
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
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib