Tsao Anne S, Moon James, Wistuba Ignacio I, Vogelzang Nicholas J, Kalemkerian Gregory P, Redman Mary W, Gandara David R, Kelly Karen
Department of Thoracic and Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
SWOG Statistical Center, Seattle, Washington.
J Thorac Oncol. 2017 Aug;12(8):1299-1308. doi: 10.1016/j.jtho.2017.05.021. Epub 2017 Jun 6.
In malignant pleural mesothelioma, targeting angiogenesis with cediranib, a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, may have therapeutic potential.
S0905 phase I combined cediranib (two dose cohorts [30 mg and 20 mg daily]) with cisplatin-pemetrexed for six cycles followed by maintenance cediranib in unresectable chemonaive patients with malignant pleural mesothelioma of any histologic subtype. The primary end point established the maximum tolerated dose in combination with cisplatin-pemetrexed in a dose deescalation scheme.
A total of 20 patients were enrolled (seven to the 30-mg cohort and 13 to the 20-mag cohort). In the cediranib 30-mg cohort, two of the initial six patients reported dose-limiting toxicities and the dose was deemed too toxic to continue. In the next cohort, two patients experienced dose-limiting toxicities, and thus, the maximum tolerated dose of cediranib was established as 20 mg. During the six cycles of cisplatin-pemetrexed-cediranib, 20 mg, there were grade 3 toxicities (neutropenia and gastrointestinal) and grade 4 thrombocytopenia. No patients had any significant episodes of bleeding. According to the Response Evaluation Criteria in Solid Tumors (n = 17 evaluable patients), the median progression-free survival was 12.8 months (95% confidence interval [CI]: 6.9-17.2); according to the Modified Response Evaluation Criteria in Solid Tumors (n = 19 evaluable patients), the median progression-free survival was 8.6 months (95% CI: 6.1-10.9). For all patients, the disease control rate at 6 weeks was 90% and median overall survival time was 16.2 months (95% CI: 10.5-28.7).
Cediranib combined with cisplatin-pemetrexed has a reasonable toxicity profile and preliminary promising efficacy. The phase II S0905 trial will evaluate the efficacy of the triplet regimen compared with the current standard of care, cisplatin-pemetrexed.
在恶性胸膜间皮瘤中，使用西地尼布（一种血管内皮生长因子受体和血小板衍生生长因子受体抑制剂）靶向血管生成可能具有治疗潜力。
S0905一期试验将西地尼布（两个剂量组[每日30毫克和20毫克]）与顺铂-培美曲塞联合使用六个周期，随后对任何组织学亚型的不可切除初治恶性胸膜间皮瘤患者进行西地尼布维持治疗。主要终点是在剂量递减方案中确定与顺铂-培美曲塞联合使用时的最大耐受剂量。
共纳入20例患者（7例进入30毫克组，13例进入20毫克组）。在西地尼布30毫克组中，最初的6例患者中有2例报告了剂量限制性毒性，该剂量被认为毒性过大无法继续。在下一组中，2例患者出现剂量限制性毒性，因此，西地尼布的最大耐受剂量确定为20毫克。在顺铂-培美曲塞-西地尼布（20毫克）的六个周期中，出现了3级毒性（中性粒细胞减少和胃肠道毒性）和4级血小板减少症。没有患者发生任何严重出血事件。根据实体瘤疗效评价标准（n = 17例可评估患者），无进展生存期的中位数为12.8个月（95%置信区间[CI]：6.9 - 17.2）；根据实体瘤改良疗效评价标准（n = 19例可评估患者），无进展生存期的中位数为8.6个月（95% CI：6.1 - 10.9）。对于所有患者，6周时的疾病控制率为90%，总生存时间中位数为16.2个月（95% CI：10.5 - 28.7）。
西地尼布联合顺铂-培美曲塞具有合理的毒性特征和初步的良好疗效。二期S0905试验将评估三联方案与当前标准治疗方案顺铂-培美曲塞相比的疗效。
