Gershenson D M, Morris M, Burke T W, Levenback C, Wolf J, Lee J J, Thall P F, Atkinson E N, Silva E G, Wharton J T
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 1999 Dec 1;86(11):2291-300.
The primary purpose of this study was to establish the maximum tolerated dose (MTD) of intravenous melphalan in combination with paclitaxel and cisplatin plus granulocyte-colony stimulating factor (G-CSF) in patients with suboptimal advanced epithelial ovarian carcinoma or primary peritoneal carcinoma.
Patients with suboptimal (>2 cm residual tumor) Stage III or Stage IV epithelial ovarian carcinoma or peritoneal carcinoma were eligible for this Phase I study. In the first stage of the study, the doses of paclitaxel and cisplatin were fixed at 135 mg/m(2) and 75 mg/ m(2), respectively, and the dose of intravenous melphalan was escalated in consecutive cohorts of 3-6 patients depending on toxicity. The planned dose escalation levels of melphalan were 6 mg/m(2), 10 mg/m(2), and 14 mg/m(2). In the second stage of the study, the doses of cisplatin and melphalan were fixed at 75 mg/m(2) and the MTD level, respectively, and the dose of paclitaxel was escalated. The planned dose escalation levels of paclitaxel were 150 mg/m(2), 175 mg/m(2), 200 mg/m(2), 225 mg/m(2), and 250 mg/m(2). G-CSF was administered for 12-19 days with each cycle, and cycles were repeated every 4 weeks for a total of 6 cycles. Other end points included clinical or surgical response, progression free survival, and survival.
Between January 1993 and May 1996, 34 women with untreated advanced stage epithelial ovarian carcinoma or primary peritoneal carcinoma were treated with 192 cycles of therapy. The MTD of melphalan was 10 mg/m(2), with the dose-limiting toxicity being thrombocytopenia. Paclitaxel was escalated to a dose level of 200 mg/m(2) with a toxicity rate of < 33%. The clinical response rate was 80% in 29 patients with measurable disease. Of 11 patients who underwent second-look surgery, 5 (45%) had a surgical pathologic complete response. The median progression free survival was 16.8 months and the median survival was 32.8 months.
The combination of intravenous melphalan, paclitaxel, and cisplatin was found to have acceptable toxicity and good activity. A Phase II study of this combination appears to be warranted.
本研究的主要目的是确定静脉注射美法仑联合紫杉醇、顺铂及粒细胞集落刺激因子（G-CSF）用于晚期上皮性卵巢癌或原发性腹膜癌患者的最大耐受剂量（MTD），这些患者初始病情不佳。
初始病情不佳（残留肿瘤>2 cm）的III期或IV期上皮性卵巢癌或腹膜癌患者符合本I期研究标准。在研究的第一阶段，紫杉醇和顺铂的剂量分别固定为135 mg/m²和75 mg/m²，静脉注射美法仑的剂量根据毒性在3至6名患者的连续队列中逐步增加。美法仑计划的剂量递增水平为6 mg/m²、10 mg/m²和14 mg/m²。在研究的第二阶段，顺铂和美法仑的剂量分别固定为75 mg/m²和MTD水平，紫杉醇的剂量逐步增加。紫杉醇计划的剂量递增水平为150 mg/m²、175 mg/m²、200 mg/m²、225 mg/m²和250 mg/m²。每个周期给予G-CSF 12至19天，每4周重复一个周期，共6个周期。其他终点包括临床或手术反应、无进展生存期和生存期。
1993年1月至1996年5月，34例未经治疗的晚期上皮性卵巢癌或原发性腹膜癌女性接受了192个周期的治疗。美法仑的MTD为10 mg/m²，剂量限制性毒性为血小板减少。紫杉醇剂量递增至200 mg/m²，毒性率<33%。29例可测量疾病患者的临床缓解率为80%。11例接受二次探查手术的患者中，5例（45%）有手术病理完全缓解。中位无进展生存期为16.8个月，中位生存期为32.8个月。
静脉注射美法仑、紫杉醇和顺铂的联合方案毒性可接受且活性良好。对该联合方案进行II期研究似乎是必要的。
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