Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study.
PURPOSE Effects of specific antineoplastic therapies on progression of cancer-associated wasting remain uncharacterized. We selected a targeted therapy, sorafenib, because of its reported association with weight loss. PATIENTS AND METHODS Patients with metastatic renal cell cancer (RCC) who were resistant to standard therapy (N = 80) received sorafenib 400 mg twice daily or placebo in a randomized, double-blinded clinical trial. Computed tomography image analysis, which has high precision and specificity for evaluation of specific muscles and adipose tissues, was used to define change in total skeletal muscle and adipose tissue. Results At inclusion, 51% of patients were overweight or obese (ie, body mass index [BMI] > 25 kg/m(2)). Only 5% were underweight. Advanced muscle wasting (ie, sarcopenia) was present in 72% of patients with BMI less than 25 and in 34% of those with a BMI greater than 25. Patients received placebo for an average of 6 months and received sorafenib for 1 year. Patients in the placebo group had stable body weight during 6 months (0.8 kg +/- 0.7 kg), with no significant alteration of muscle or fat. Patients who received sorafenib lost 2.1 kg +/- 0.6 kg (P < .01) in 6 months and lost 4.2 kg +/- 0.7 kg (P < .01) by 1 year. Sorafenib-treated patients lost skeletal muscle progressively at 6 months (decrease of 4.9%; P < .01) and 12 months (decrease of 8.0%; P < .01). CONCLUSION Sarcopenia is prevalent in patients with metastatic RCC and is an occult condition in patients with normal or high BMI. Muscle loss is specifically exacerbated by sorafenib, consistent with the evidence for a role of kinases in regulating muscle mass. Muscle loss is a sorafenib adverse effect that may relate to asthenia, fatigue, and physical disability.
Antoun
Sami
S
Department of Supportive Care, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. sami.antoun@igr.fr
Birdsell
Laura
L
Sawyer
Michael B
MB
Venner
Peter
P
Escudier
Bernard
B
Baracos
Vickie E
VE
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects*; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010919:Placebos; D011379:Prognosis; D011725:Pyridines / Q000009:adverse effects*; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome; D019282:Wasting Syndrome / Q000139:chemically induced* / Q000473:pathology
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D010919:Placebos; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib