Theou-Anton Nathalie, Faivre Sandrine, Dreyer Chantal, Raymond Eric
Department of Pharmacy, Beaujon University Hospital-Paris 7, Hôpital Beaujon, Clichy, France.
Drug Saf. 2009;32(9):717-34. doi: 10.2165/00002018-200932090-00003.
Sunitinib is a novel, oral, multi-targeted tyrosine kinase inhibitor with antiproliferative effects against cancer cells and antiangiogenic properties. Sunitinib was recently approved for the first-line treatment of patients with advanced renal cell carcinoma (RCC) and for the treatment of patients with gastrointestinal stromal tumours (GIST) after disease progression or intolerance to imatinib therapy. The main purpose of this benefit-risk assessment is to review data on sunitinib efficacy along with its toxicity in patients with GIST and RCC. Sunitinib demonstrates a high level of efficacy with acceptable tolerability using either the 50 mg daily oral dosing for 4 weeks every 6 weeks or a continuous daily administration schedule at a lower dose. Hypertension and asthenia appear to be the most common adverse effects with sunitinib. Diarrhoea, anorexia, disgeusia, stomatitis and skin toxicity are other clinically relevant toxicities. Fatigue may, at least in part, be related to the development of hypothyroidism during sunitinib therapy. Skin toxicity consists of bullous lesion in the soles and palms that may require treatment discontinuation for a few days and/or dose reduction. Thyroid hormone levels should be monitored during treatment with sunitinib, with the occurrence of clinical signs of hypothyroidism needing treatment with levothyroxine sodium. Hypertension usually requires standard antihypertensive therapy and treatment discontinuation is less frequently necessary. Mild neutropenia and thrombocytopenia usually require no intervention. A decrease in left ventricular ejection fraction is a rare but potentially life-threatening complication. Although usually well tolerated, sunitinib needs to be administered cautiously with medical follow-up in patients with cancer to prevent, avoid and treat adverse effects in order to improve patient compliance. Its established antitumor activity requires attempting to maintain the highest tolerable dose in individual patients. Current oral formulations allow physicians to modulate dosages (between 25 and 50 mg/day) and/or schedules (4 weeks on, 2 weeks off or continuous administration) to optimize the benefit-risk profile of sunitinib in individual patients.
舒尼替尼是一种新型口服多靶点酪氨酸激酶抑制剂，具有抗癌细胞增殖作用和抗血管生成特性。舒尼替尼最近被批准用于晚期肾细胞癌（RCC）患者的一线治疗，以及用于疾病进展或对伊马替尼治疗不耐受的胃肠道间质瘤（GIST）患者的治疗。这项获益-风险评估的主要目的是回顾舒尼替尼在GIST和RCC患者中的疗效及毒性数据。使用每6周每日口服50 mg共4周的给药方案或较低剂量的持续每日给药方案时，舒尼替尼显示出高效且耐受性可接受。高血压和乏力似乎是舒尼替尼最常见的不良反应。腹泻、厌食、味觉障碍、口腔炎和皮肤毒性是其他临床相关毒性。疲劳可能至少部分与舒尼替尼治疗期间甲状腺功能减退的发生有关。皮肤毒性表现为足底和手掌的大疱性病变，可能需要停药数天和/或减少剂量。在舒尼替尼治疗期间应监测甲状腺激素水平，出现甲状腺功能减退的临床体征时需要用左甲状腺素钠治疗。高血压通常需要标准的抗高血压治疗，很少需要停药。轻度中性粒细胞减少和血小板减少通常无需干预。左心室射血分数降低是一种罕见但可能危及生命的并发症。尽管舒尼替尼通常耐受性良好，但在癌症患者中使用时仍需要谨慎给药并进行医学随访，以预防、避免和治疗不良反应，从而提高患者的依从性。其已确立的抗肿瘤活性要求尝试在个体患者中维持最高可耐受剂量。目前的口服制剂使医生能够调整剂量（25至50 mg/天之间）和/或给药方案（4周用药，2周停药或持续给药），以优化舒尼替尼在个体患者中的获益-风险状况。
