Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer
Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer
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DOI：
10.1200/jco.1997.15.1.187
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发表时间：
1997-01-01
影响因子：
45.3
通讯作者：
Spriggs, D
中科院分区：
文献类型：
--
作者：
Fennelly, D;Aghajanian, C;Spriggs, D
目的：紫杉醇在晚期卵巢癌治疗中显示出显著的活性。紫杉醇的体外研究表明，分次短时间的输液程序可能比标准的24小时输液更有效。我们开始了对复发性卵巢癌患者每周递增剂量紫杉醇(40，50，60，80,100 mg/m(2))1小时输注的I期评估。所有患者都曾接受过紫杉醇和顺铂治疗，所有患者都接受了标准的前期药物治疗。患者和方法：18名患者可在I期研究中进行评估。年龄48~74岁，平均54岁。既往化疗2~5个月，平均10.1个月(1~24个月)。结果：共治疗194个周期，平均10个周期(1~12个周期)。18例可评价患者中1例出现脱发，中性粒细胞最低值为4.0×10(9)/L。在最大剂量水平(100 mg/m(2))下，剂量强度为计划的90.75%，超过标准剂量强度的2倍。13例可评估患者中有4例出现部分反应(30%)。两名病情进展的患者按照标准的三周紫杉醇方案转换为每周方案，并显示出有效。增加紫杉醇剂量与测量的曲线下面积(AUC)相关(R(2)=.614)。剂量限制毒性达到100 mg/m(2)，三个患者中有两个经历了治疗延迟，从而定义了这组每周大量接受紫杉醇治疗的患者的最大耐受剂量为80 mg/m(2)。结论：(1)紫杉醇作为1小时输注的耐受性很好；(2)这个给药方案不会导致累积的骨髓抑制；(3)这个给药方案导致了剂量密集型紫杉醇的给药，具有良好的毒性特征。(C)1997年，由美国临床肿瘤学会主办。
Purpose: Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m(2)) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy, All patients received standard premedication.Patients and Methods: Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five), The mean paclitaxel-free interval was 10.1 months (range, 1 to 24).Results: A total of 194 cycles of therapy were administered with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen, Alopecia occurred in one out of 18 assessable patients, The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m(2)) delivered, dose-intensity was 90.75% of that planned and greeter than two fold the standard dose-intensity. partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R(2) = .614). Dose-limiting toxicity was reached at 100 mg/m(2) with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m(2) in this group of heavily pretreated patients on this weekly schedule.Conclusion: (1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile. (C) 1997 by American Society of Clinical Oncology.