title: Sunitinib: new drug. For some gastrointestinal stromal tumours.
abstract: (1) Sunitinib, a tyrosine kinase inhibitor, is marketed for the treatment of advanced-stage and metastatic renal carcinoma, and for second-line treatment of gastrointestinal stromal tumours. Sorafenib arrived on the market almost simultaneously for second-line treatment of kidney cancer. (2) In second-line treatment of kidney cancer, two non comparative trials showed an unusually high rate of at least partial tumour regression with sunitinib (25%, compared to only 2% with sorafenib). Head-to-head trials of the two drugs are lacking. Although indirect comparisons are notoriously unreliable, sunitinib appears to provide longer progression-free survival than sorafenib (about 9 months versus 5.5 months), although overall survival times are similar. (3) Preliminary results of a trial comparing sunitinib with interferon alfa as first-line treatments in 750 patients with kidney cancer show a 6-month event-free survival advantage in the sunitinib arm. The precise overall survival time has not yet been calculated. (4) In 312 patients with gastrointestinal stromal tumours in whom imatinib has failed, a double-blind placebo-controlled trial showed that sunitinib prolonged overall survival time, but potential biases undermine these results. (5) The adverse effect profile of sunitinib appears to be similar to those of imatinib and sorafenib, apart from more thyroid disorders. The principal adverse effects are cutaneous, gastrointestinal, cardiovascular and haematological disorders. Arterial hypertension, sometimes severe, occurred in 16% of patients treated with sunitinib. Other serious adverse events included tumour haemorrhage and pulmonary embolism. A risk of cardiac toxicity leading to heart failure cannot currently be ruled out. (6) Sunitinib is metabolised by cytochrome P450 isoenzyme CYP 3A4, increasing the likelihood of drug interactions. (7) These results support the use of sunitinib as second-line therapy for patients with gastrointestinal stromal tumours. Additional clinical evaluation is needed, however. In first-line treatment of kidney cancer, it is preferable to wait for detailed results of the ongoing trial, especially effects on survival time, before judging the possible advantages and disadvantages of sunitinib compared to interferon alfa. In second-line treatment, sorafenib is better-assessed than sunitinib and should therefore be preferred, pending a direct comparison of the two drugs.
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D046152:Gastrointestinal Stromal Tumors / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D007037:Hypothyroidism / Q000150:complications; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases