Lilenbaum R C, MacManus D, Engstrom C, Green M
University of Maryland Cancer Center, Baltimore, USA.
Am J Clin Oncol. 1998 Apr;21(2):129-34. doi: 10.1097/00000421-199804000-00006.
The authors define the dose-limiting toxicities and the recommended phase II doses of paclitaxel combined with etoposide, without and with filgrastim support. Patients with advanced solid tumors were eligible if they had a performance status of 0 to 2 and normal renal, hepatic, and bone marrow function. Patients with cardiac arrhythmias or congestive heart failure requiring medical therapy were excluded. Prior radiation was allowed only if it involved less than 30% of the marrow-containing skeleton. The dose of etoposide was fixed at 100 mg/m2/d for 3 days beginning on day 1. Paclitaxel was administered over 3 hours on day 4. The dose of paclitaxel was escalated until the maximum tolerated dose (MTD), without and with filgrastim 5 microg/kg (or 300 microg total dose) subcutaneously beginning on day 5, was reached. Treatment cycles were repeated every 21 days. Of 39 patients entered, 37 were evaluable for toxicity and 30 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 150 mg/m2. With filgrastim, the dose of paclitaxel was escalated to 250 mg/m2 in combination with etoposide 100 mg/m2. One episode of pulmonary toxicity was observed. Five patients responded: two with previously treated non-small-cell lung cancer (NSCLC), two with refractory small-cell lung cancer (SCLC), and one with refractory germ-cell tumor (GCT). We conclude that paclitaxel and etoposide can be given in combination at clinically relevant doses with filgrastim support. In this phase I trial, a dose of paclitaxel of 200 mg/m2 on day 4 and etoposide at 100 mg/m2/d on days 1-3, with filgrastim 5 microg/kg beginning on day 5, was found to be well tolerated, and can be recommended for future studies. Without filgrastim, a paclitaxel dose of 150 mg/m2 with the same dose of etoposide can also be recommended.
作者明确了紫杉醇联合依托泊苷在有无非格司亭支持情况下的剂量限制性毒性以及推荐的II期剂量。晚期实体瘤患者若体能状态为0至2且肾、肝和骨髓功能正常，则符合入组条件。患有需要药物治疗的心律失常或充血性心力衰竭的患者被排除。仅当先前放疗涉及的含骨髓骨骼部位少于30%时才允许。依托泊苷剂量固定为100mg/m²/天，从第1天开始连用3天。紫杉醇在第4天静脉滴注3小时。紫杉醇剂量逐步递增直至达到最大耐受剂量（MTD），分别在有无从第5天开始皮下注射非格司亭5μg/kg（或总剂量300μg）的情况下进行。治疗周期每21天重复一次。入组的39例患者中，37例可评估毒性，30例可评估疗效。主要毒性为中性粒细胞减少。在没有非格司亭的情况下，紫杉醇的MTD为150mg/m²。在有非格司亭的情况下，紫杉醇剂量递增至250mg/m²并联合100mg/m²的依托泊苷。观察到1例肺部毒性。5例患者有反应：2例为先前治疗过的非小细胞肺癌（NSCLC），2例为难治性小细胞肺癌（SCLC），1例为难治性生殖细胞肿瘤（GCT）。我们得出结论，在非格司亭支持下，紫杉醇和依托泊苷可以临床相关剂量联合使用。在这项I期试验中，发现第4天给予200mg/m²的紫杉醇、第1 - 3天给予100mg/m²/天的依托泊苷并从第5天开始给予5μg/kg非格司亭的方案耐受性良好，可推荐用于未来研究。在没有非格司亭的情况下，也可推荐150mg/m²的紫杉醇联合相同剂量的依托泊苷。
