Porta Camillo, Szczylik Cezary
Medical Oncology, IRCCS San Matteo University Hospital Foundation, Piazzale C. Golgi 19, I-27100 Pavia, Italy.
Cancer Treat Rev. 2009 May;35(3):297-307. doi: 10.1016/j.ctrv.2008.12.003. Epub 2009 Feb 26.
The treatment options for metastatic renal cell carcinoma have expanded rapidly over the past 3 years, with four new agents available and others in late-stage development. This has resulted in a change of the standard of first-line care, with sunitinib or bevacizumab plus interferon the treatments of choice for patients with good or intermediate-risk renal cell carcinoma and temsirolimus treatment of choice for poor-risk disease. Sunitinib and bevacizumab plus interferon have similar efficacy, meaning that treatment choice is influenced by other factors: disease-related factors such as clear cell versus non-clear cell histology; patient factors such as co-morbidities, Memorial Sloan-Kettering Cancer Center risk and patient preference; and drug-related factors such as tolerability profile. The aim of this review is to describe the tolerability of the first-line treatment options for clear cell renal cell carcinoma, giving consideration to how tolerability profiles relate to drug mechanism of action. Thus, the incidence and aetiology of side effects related to vascular endothelial growth factor and vascular endothelial growth factor receptor inhibition using sunitinib and bevacizumab, as well as those of the non-specific side effects observed with sunitinib, are described. In addition, the potential patient impact and management of these side effects, as well as those of interferon and temsirolimus, are considered. Finally, the implications of the tolerability profiles of these agents for combination therapy and use in broader populations than those enrolled in trials are assessed.
在过去3年中，转移性肾细胞癌的治疗选择迅速增加，有4种新药可供使用，其他药物也处于后期研发阶段。这导致了一线治疗标准的改变，舒尼替尼或贝伐单抗联合干扰素成为中低危肾细胞癌患者的首选治疗方案，而替西罗莫司则是高危疾病的首选治疗药物。舒尼替尼和贝伐单抗联合干扰素具有相似的疗效，这意味着治疗选择受其他因素影响：疾病相关因素，如透明细胞与非透明细胞组织学；患者因素，如合并症、纪念斯隆凯特琳癌症中心风险评估及患者偏好；以及药物相关因素，如耐受性。本综述的目的是描述透明细胞肾细胞癌一线治疗方案的耐受性，并考虑耐受性与药物作用机制的关系。因此，本文描述了使用舒尼替尼和贝伐单抗抑制血管内皮生长因子和血管内皮生长因子受体相关副作用的发生率和病因，以及舒尼替尼观察到的非特异性副作用。此外，还考虑了这些副作用对患者的潜在影响及管理方法，以及干扰素和替西罗莫司副作用的相关情况。最后，评估了这些药物耐受性对联合治疗的影响，以及在比试验入组人群更广泛的人群中的应用情况。
