Homesley H, Benigno B, Williams J, Vaccarello L
Brookview Research Inc. Nashville, Tennessee 37203, USA.
Gynecol Oncol. 2002 Nov;87(2):171-7. doi: 10.1006/gyno.2002.6811.
We have previously reported on the feasibility of weekly topotecan as single-agent therapy in previously treated patients with ovarian cancer. The objective of this study was to assess the maximum tolerated dose (MTD) of weekly bolus intravenous (IV) topotecan combined with weekly paclitaxel in a comparable patient population.
Previously treated ovarian cancer patients with measurable disease and/or elevated cancer antigen 125 (CA-125) received (as second-line or third-line therapy) weekly 30-min bolus IV topotecan starting at 2 mg/m(2) combined with weekly paclitaxel starting at a dose of 60 mg/m(2). In this intrapatient dose-escalation study, topotecan and paclitaxel were escalated in parallel until the MTD was reached, defined as the first dose level at which >or= 2 of 6 patients experienced dose-limiting toxicity.
Twenty-one of 26 patients were evaluable for toxicity and received a total of 306 weeks of therapy (median, 13 weeks; range, 5 to 33 weeks). No significant dose-limiting toxicity was observed up to a weekly bolus IV topotecan dose of 3 mg/m(2) and a concurrent paclitaxel dose of 80 mg/m(2). The MTD was topotecan 3.5 mg/m(2) plus 90 mg/m(2) paclitaxel. The dose-limiting toxicities included anemia and fatigue, with 10 of 21 patients receiving epoetin alfa for grade 3 or 4 anemia; only 1 patient required a blood transfusion. Two patients had a treatment delay of at least 1 week and only 1 patient required a dose reduction to maintain the weekly schedule.
Based on the results of this study, the recommended initial dose for this novel regimen is topotecan 3 mg/m(2) and paclitaxel 80 mg/m(2). Further investigation of the efficacy of weekly topotecan plus paclitaxel in less heavily pretreated patients is warranted.
我们之前报道了拓扑替康单药每周疗法用于既往接受过治疗的卵巢癌患者的可行性。本研究的目的是评估在类似患者群体中，每周大剂量静脉注射拓扑替康联合每周紫杉醇的最大耐受剂量（MTD）。
既往接受过治疗且有可测量病灶和/或癌抗原125（CA-125）升高的卵巢癌患者（作为二线或三线治疗），接受每周一次、持续30分钟的大剂量静脉注射拓扑替康（起始剂量为2mg/m²）联合每周一次紫杉醇（起始剂量为60mg/m²）。在这项患者内剂量递增研究中，拓扑替康和紫杉醇并行递增，直至达到MTD，MTD定义为6名患者中至少2名出现剂量限制性毒性的首个剂量水平。
26例患者中有21例可进行毒性评估，共接受了306周的治疗（中位数为13周；范围为5至33周）。在每周大剂量静脉注射拓扑替康剂量达3mg/m²且同时紫杉醇剂量达80mg/m²时，未观察到明显的剂量限制性毒性。MTD为拓扑替康3.5mg/m²加紫杉醇90mg/m²。剂量限制性毒性包括贫血和疲劳，21例患者中有10例因3级或4级贫血接受了促红细胞生成素α治疗；仅1例患者需要输血。2例患者治疗延迟至少1周，仅1例患者需要减量以维持每周治疗方案。
基于本研究结果，该新方案的推荐初始剂量为拓扑替康3mg/m²和紫杉醇80mg/m²。有必要进一步研究每周拓扑替康加紫杉醇在预处理程度较轻患者中的疗效。
