A phase II trial of three sequential doublets for the treatment of advanced mullerian malignancies
A phase II trial of three sequential doublets for the treatment of advanced mullerian malignancies
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DOI：
10.1016/s0090-8258(03)00496-7
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发表时间：
2003-11-01
影响因子：
4.7
通讯作者：
Seiden, MV
中科院分区：
文献类型：
--
作者：
Matulonis, U;Campos, S;Seiden, MV
客观的。为了改善苗勒氏管恶性肿瘤主要化疗的结果，试验了一种新的化疗方案，该方案提供了三个连续化疗双联。主要终点是手术确定的缓解率和毒性评估。方法。初次细胞减灭手术后，患者接受三个连续双联治疗，包括三个初始周期的卡铂和紫杉醇（双联 1），然后两个周期的顺铂（第 1 天）和吉西他滨（第 1 天和第 8 天；双联 2），最后两个周期的阿霉素（第 1 天）和拓扑替康（第 3,4 和 5 天；双联 3）。第 4 至 7 周期以 5 mcg/kg/天的剂量给予 G-CSF (Neupogen) 支持。治疗后，如果临床分期残留病灶呈阴性，则对所有女性进行临床分期并通过二次腹腔镜检查/剖腹手术 (SLO) 进行评估。结果。共有 49 名符合条件的患者入组，中位年龄为 52 岁 (SD 9)。 44 名女性患有卵巢癌或原发性腹膜癌，其中 3 名女性诊断为输卵管癌，2 名女性诊断为子宫乳头状浆液性癌。 84% 的患者患有 IIIC/IV 期肿瘤，其中 29% 在初次细胞减灭术后有 > 1 cm 的残留病灶。 49 名患者中的 39 名 (80%) 完成了治疗。总共进行了 283 个周期的化疗，毒性可接受。没有发生中毒死亡事件。 5 名女性退出试验（3 名女性因紫杉醇过敏，1 名女性因吉西他滨肺部过敏，1 名女性因严重导管感染）。中性粒细胞减少症（通常不伴有发烧）在第一组中相对常见。恶心和血小板减少是双组 2 中的主要毒性。39 名女性完成了所有治疗周期。 36 名女性的重新分期结果与临床完全缓解 (CR) 一致，并接受了 SLO。接受SLO治疗的患者病理CR率为38%。结论。采用这种序贯双重方案治疗是可行的，病理 CR 率为 38%。 (C) 2003 Elsevier Inc. 保留所有权利。
Objective. In an effort to improve the results of primary chemotherapy for mullerian malignancies a novel chemotherapy program was piloted that delivered three sequential chemotherapy doublets. The primary endpoints were surgically defined response rates and evaluation of toxicity.Methods. After primary cytoreductive surgery patients were treated with three sequential doublets including three initial cycles of carboplatin and paclitaxel (doublet 1) and then two cycles of cisplatin (day 1) and gemcitabine (days I and 8; doublet 2), and finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet 3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5 mcg/kg/day. After therapy, all women were clinically staged and evaluated by second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for residual disease.Results. A total of 49 eligible patients were enrolled with a median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2 with papillary serous carcinoma of the uterus. Eighty-four percent of patients had stage lIIc/IV tumors, with 29% having > I cm residual disease after primary cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A total of 283 cycles of chemotherapy were delivered with acceptable toxicities. There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol hypersensitivity, I for gemcitabine pulmonary hypersensitivity, and I for serious line infection). Neutropenia, typically without fever, was relatively frequent in the first doublet. Nausea and thrombocytopenia were the predominant toxicities in doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women had restaging results consistent with a clinical complete response (CR) and underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%.Conclusions. Treatment with this sequential doublet regimen is feasible with a 38% pathologic CR rate. (C) 2003 Elsevier Inc. All rights reserved.