Carboplatin and paclitaxel in ovarian carcinoma: A phase I study of the Gynecologic Oncology Group
Carboplatin and paclitaxel in ovarian carcinoma: A phase I study of the Gynecologic Oncology Group
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DOI：
10.1200/jco.1996.14.6.1895
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发表时间：
1996-06-01
影响因子：
45.3
通讯作者：
Ozols, RF
中科院分区：
文献类型：
--
作者：
Bookman, MA;McGuire, WP;Ozols, RF
目的：为了开发一种可耐受的，剂量密集的卡铂和紫杉醇治疗方案原发性上皮性卵巢carcinoma.Patients和方法：患者进行了初步的手术评估和肿瘤减积。III/IV期患者在计划的21天周期中接受6个周期的化疗。根据浓度随时间的曲线下面积（AUC）计算卡铂剂量（mg）。mL（-1）。min），并递增以确定最大耐受剂量（MTD）。Paclitaxel剂量也逐步增加为3-，24-，或96小时输注，粒细胞集落刺激因子（G-CSF）需要在选定的剂量水平或可以添加基于血液toxicity.Results：39例患者入组和评估的毒性和反应。剂量限制性毒性（DLT）为血液学毒性，主要为中性粒细胞减少。少于2%的紫杉醇3小时或24小时输注周期与4级血小板减少症或发热性中性粒细胞减少症相关。卡铂的MTD为AUC 7.5（相当于中位剂量471 mg/m2）。在没有初始G-CSF的情况下，紫杉醇的MTD为24小时135 mg/m2，3小时175 mg/m2。紫杉醇120 mg/m2 96小时输注与过度的单周期和累积骨髓抑制相关，未进一步评估，测量的卡铂AUC与计算的AUC一致。24例可测量疾病患者的总体完全缓解率（n = 16）和部分缓解率（n = 2）为75%，中位无进展生存期为15个月。卡铂可以安全地与紫杉醇联合使用基于预计肾清除率的剂量公式，推荐的门诊治疗方案是卡铂AUC 7.5和紫杉醇175 mg/m2，3小时内给药，不使用初始G-CSF。该治疗安全地实现了比基于体表面积的常规给药所实现的更大的卡铂剂量强度。(C)1996年，美国临床肿瘤学会。
Purpose: To develop a tolerable, dose-intense regimen of carboplatin and paclitaxel for the treatment of primary epithelial ovarian carcinoma.Patients and Methods: Patients underwent initial surgical assessment and tumor debulking. patients with stage III/IV disease received six cycles of chemotherapy on a planned 21-day cycle. Carboplatin dose was calculated based on projected area under the curve (AUG) for concentration over time (mg . mL(-1). min) and escalated to determine the maximum-tolerated dose (MTD). Paclitaxel dose was also escalated as a 3-, 24-, or 96-hour infusion, Granulocyte colony-stimulating factors (G-CSFs) were required at selected dose levels or could be added based on hematologic toxicity.Results: Thirty-nine patients were enrolled and assessable for toxicity and response. Dose-limiting toxicity (DLT) was hematologic, primarily neutropenia. Less than 2% of all cycles with paclitaxel as a 3- or 24-hour infusion were associated with either grade 4 thrombocytopenia or febrile neutropenia. The carboplatin MTD was AUC 7.5 (equivalent to a median dose of 471 mg/m(2)). The MTD for paclitaxel was 135 mg/m(2) over 24 hours and 175 mg/m(2) over 3 hours without initial G-CSF. A 96-hour infusion of paclitaxel at a dose of 120 mg/m(2) was associated with excessive single-cycle and cumulative myelosuppression, and was not further evaluated, Measured carboplatin AUC agreed well with the calculated AUC. The overall complete (n = 16) and partial (n = 2) response rate among 24 patients with measurable disease was 75%, with a median progression-free survival time of 15 months.Conclusion: Carboplatin could be safely combined with paclitaxel using a dose formula based on projected renal clearance, The recommended outpatient regimen is carboplatin AUC 7.5 and paclitaxel 175 mg/m(2) over 3 hours without initial G-CSF. This treatment safely achieved a greater dose-intensity of carboplatin than would have been achieved with conventional dosing based on body-surface area. (C) 1996 by American Society of Clinical Oncology.