Sorafenib: new drug. Second-line treatment of kidney cancer: better evaluated than sunitinib.
(1) Kidney cancer is infrequent. Most renal malignancies are adenocarcinomas. The prognosis varies markedly from one patient to another. Interferon alfa generally increases survival time by a few months in patients with locally advanced or metastatic cancers, but it has a negative impact on quality of life. (2) Sorafenib inhibits several kinases implicated in angiogenesis and tumour growth. It was recently approved for second-line treatment of advanced-stage kidney cancer. (3) A double-blind placebo-controlled trial involving 903 patients evaluated second-line sorafenib therapy at an oral dose of 400 mg twice a day. Patients with a poor prognosis were not eligible. (4) Sorafenib increased overall survival time by about three months (50% mortality was reached at 19 months in the sorafenib group and at 16 months in the placebo group). The median progression-free survival time also increased by about three months (5.5 months with sorafenib versus about 3 months with placebo). The impact of sorafenib on quality of life was not reported. (5) An indirect comparison shows a higher rate of tumour regression with sunitinib than with sorafenib (25% versus 2%), and also longer progression-free survival (3 to 4 months longer with sunitinib). However, there was no difference between the two drugs in overall survival time, which is the most relevant outcome. Note that no practical conclusions can be drawn from indirect comparisons of this type, as they are subject to too many biases. (6) The main adverse events among patients treated with sorafenib in this trial were cutaneous disorders (about 30% of patients), diarrhoea (about 20%), hypertension (10%), and bleeding (10%). Cases of myocardial ischaemia and neuropathies also occurred. (7) Sorafenib is teratogenic in several animal species. (8) Sorafenib is metabolised by the cytochrome P450 isoenzyme CYP 3A4. The risk of clinically relevant drug interactions is poorly documented. (9) For second-line treatment of patients with kidney cancer and no factors of poor prognosis, available data favour the use of sorafenib, which is better assessed than sunitinib.
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D040262:Receptors, Vascular Endothelial Growth Factor