Omura George A, Brady Mark F, Look Katherine Y, Averette Hervy E, Delmore James E, Long Harry J, Wadler Scott, Spiegel Gregory, Arbuck Susan G
University of Alabama at Birmingham, Birmingham, AL, USA.
J Clin Oncol. 2003 Aug 1;21(15):2843-8. doi: 10.1200/JCO.2003.10.082. Epub 2003 Jun 13.
To determine if increasing the dose of paclitaxel increases the probability of clinical response, progression-free survival, or overall survival in women who have persistent or recurrent ovarian cancer, and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever.
Consenting patients with persistent, recurrent, or progressing ovarian cancer, despite first-line platinum therapy (but no prior taxane), were randomly assigned to paclitaxel 135 mg/m2, 175 mg/m2, or 250 mg/m2 over 24 hours every 3 weeks. Patients receiving paclitaxel 250 mg/m2 were also randomly assigned to 5 or 10 microg/kg of filgrastim per day subcutaneously.
Accession to the paclitaxel 135-mg/m2 arm was closed early. Among the 271 patients on the other regimens with measurable disease, partial and complete response on paclitaxel 250 mg/m2 (36%) was significantly higher than on 175 mg/m2 (27%, P =.027). This difference was more evident among patients who never responded to prior platinum. However, progression-free and overall survival results were similar. The median durations of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m2 and 250 mg/m2, respectively. Thrombocytopenia, neuropathy, and myalgia were greater with paclitaxel 250 mg/m2 (P <.05). The incidence of neutropenic fever after the first cycle of paclitaxel 250 mg/m2 was 19% and 18% on the 5-microg/kg and 10-microg/kg filgrastim dose, respectively (22% for paclitaxel 175 mg/m2 without filgrastim).
Paclitaxel exhibits a dose effect with regard to response rate, but there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m2 plus filgrastim. Doubling the filgrastim dose from 5 to 10 microg/kg did not reduce the probability of neutropenic fever after high-dose paclitaxel.
确定增加紫杉醇剂量是否会提高持续性或复发性卵巢癌女性患者出现临床缓解、无进展生存期或总生存期的概率，以及将预防性非格司亭的剂量随较高剂量紫杉醇加倍是否会降低中性粒细胞减少性发热的发生率。
尽管接受了一线铂类治疗（但未接受过紫杉烷类治疗），仍同意参与研究的持续性、复发性或进展性卵巢癌患者，每3周随机分配接受24小时内静脉滴注135mg/m²、175mg/m²或250mg/m²的紫杉醇治疗。接受250mg/m²紫杉醇治疗的患者还随机分配接受每日皮下注射5μg/kg或10μg/kg的非格司亭治疗。
紫杉醇135mg/m²治疗组的入组提前结束。在接受其他治疗方案且具有可测量疾病的271例患者中，250mg/m²紫杉醇治疗组的部分缓解和完全缓解率（36%）显著高于175mg/m²治疗组（27%，P = 0.027）。这种差异在既往对铂类治疗无反应的患者中更为明显。然而，无进展生存期和总生存期结果相似。紫杉醇175mg/m²和250mg/m²治疗组的总生存期的中位持续时间分别为13.1个月和12.3个月。250mg/m²紫杉醇治疗组的血小板减少、神经病变和肌痛更为严重（P < 0.05）。250mg/m²紫杉醇治疗的第一个周期后，5μg/kg和10μg/kg非格司亭剂量组的中性粒细胞减少性发热发生率分别为19%和18%（175mg/m²紫杉醇未使用非格司亭治疗组为22%）。
紫杉醇在反应率方面呈现剂量效应，但250mg/m²紫杉醇加非格司亭治疗存在更多毒性且无生存获益。将非格司亭剂量从5μg/kg加倍至10μg/kg并不能降低高剂量紫杉醇治疗后中性粒细胞减少性发热的概率。
