Patel Premal H, Senico Peggy L, Curiel Rafael E, Motzer Robert J
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
Clin Genitourin Cancer. 2009 Jan;7(1):24-7. doi: 10.3816/CGC.2009.n.004.
Concurrent inhibition of multiple oncogenic signaling pathways might improve the efficacy of anticancer agents and abrogate resistance mechanisms. This phase I study evaluated temsirolimus in combination with sunitinib in patients with advanced RCC.
Eligibility included advanced RCC and <or= 2 previous systemic regimens. At the starting dose, temsirolimus 15 mg was administered by intravenous (I.V.) infusion once weekly, and sunitinib 25 mg was administered orally once daily for 4 weeks, followed by a 2-week rest period.
In the first cohort, dose-limiting toxicities (grade 3 treatment-related toxicities that lasted >or= 7 days) were observed in 2 of 3 patients. One patient experienced grade 3 rash during week 3, which led to treatment discontinuation. A second patient had grade 3 thrombocytopenia (platelet count, 48,000/microL), cellulitis, and gout during week 3 and was hospitalized; platelets recovered to 109,000/microL 4 days after discontinuation of protocol therapy. A third patient experienced rash, asthenia, diarrhea, stomatitis, constipation, fever, and rectal hemorrhage, all of which were mild in severity. The study was terminated because of dose-limiting toxicity observed at low starting doses of both agents.
Concomitant use of I.V. temsirolimus 15 mg weekly and oral sunitinib 25 mg daily (4 weeks on, 2 weeks off) is not recommended.
同时抑制多种致癌信号通路可能会提高抗癌药物的疗效并消除耐药机制。本I期研究评估了替西罗莫司联合舒尼替尼治疗晚期肾细胞癌（RCC）患者的疗效。
入选标准包括晚期RCC且既往接受过≤2种全身治疗方案。起始剂量为，替西罗莫司15 mg通过静脉输注每周1次，舒尼替尼25 mg口服每日1次，持续4周，随后休息2周。
在第一个队列中，3例患者中有2例出现剂量限制性毒性（3级与治疗相关的毒性，持续≥7天）。1例患者在第3周出现3级皮疹，导致治疗中断。另1例患者在第3周出现3级血小板减少（血小板计数为48,000/μL）、蜂窝织炎和痛风，并住院治疗；在停用方案治疗4天后血小板恢复至109,000/μL。第3例患者出现皮疹、乏力、腹泻、口腔炎、便秘、发热和直肠出血，所有这些症状严重程度均较轻。由于在两种药物的低起始剂量下均观察到剂量限制性毒性，该研究终止。
不推荐每周静脉注射15 mg替西罗莫司与每日口服25 mg舒尼替尼联合使用（4周用药，2周停药）。
