Three sequential chemotherapy doublets for the treatment of newly diagnosed advanced mullerian malignancies: The modified triple doublet regimen
Three sequential chemotherapy doublets for the treatment of newly diagnosed advanced mullerian malignancies: The modified triple doublet regimen
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DOI：
10.1016/j.ygyno.2006.04.017
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发表时间：
2006-11-01
影响因子：
4.7
通讯作者：
Seiden, M. V.
中科院分区：
文献类型：
--
作者：
Matulonis, U. A.;Campos, S.;Seiden, M. V.
目标。以前，我们报道了在治疗新诊断和晚期缪勒管恶性肿瘤的妇女中使用三个连续双药（三重双药）。手术定义的阴性复视手术（SLO）率为38%。对该治疗方案进行了修改，预计可以降低毒性并可能提高疗效。开放标签双队列研究。新诊断为II-IV期苗勒管恶性肿瘤的患者符合条件。细胞减缩手术后，患者接受卡铂和吉西他滨3个周期、卡铂和紫杉醇3个周期、阿霉素和拓扑替康3个周期的序贯双药治疗。治疗后，所有女性均进行临床分期，如果临床分期为阴性，则进行SLO评估。主要终点是毒性和阴性SLO率，在最佳细胞减少（队列1）和次最佳细胞减少或IV期（队列2）中分别确定了60%和40%的比率。85名符合条件的患者入组，中位年龄为52岁。第1组和第2组分别有47名和38名妇女。723个化疗周期无中毒性死亡。在至少一个治疗周期内，3级和4级毒性包括75%的患者中性粒细胞减少和65%的患者血小板减少。3.5%的患者出现发热和中性粒细胞减少。3级和4级非血液学毒性发生率均< 10%。70名妇女接受了SLO，其中SLO阴性率为53%，另外9%的人接受了显微镜下的阳性检查。队列1的SLO阴性率为74%，队列2为36%。改良的三重双重治疗方案是可耐受的，病理CR率令人鼓舞。(c) 2006爱思唯尔公司版权所有。
Objective. Previously, we reported the use of three sequential doublets (Triple Doublets) in the treatment of women with newly diagnosed and advanced stage mullerian malignancies. The surgically defined negative second look operation (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment regimen that were predicted to reduce toxicity and possibly increase efficacy.Methods. Open label two-cohort study. Patients with a new diagnosis of Stages II-IV mullerian malignancy were eligible. After cytoreductive surgery, patients were treated with three sequential doublets including 3 cycles of carboplatin and gemcitabine, and 3 cycles of carboplatin and paclitaxel, and 3 cycles of doxorubicin and topotecan. After therapy, all women were clinically staged and evaluated at SLO if clinical staging was negative for residual disease. Primary endpoints were toxicity and negative SLO rate with rates of 60% and 40% defined a priori in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or Stage IV (cohort 2), respectively.Results. Eighty-five eligible patients were enrolled with a median age of 52 years. Forty-seven and thirty-eight women were in cohorts 1 and 2, respectively. 723 cycles of chemotherapy were delivered with no toxic deaths. Grades 3 and 4 toxicities included neutropenia in 75% of patients and thrombocytopenia in 65% of patients during at least one cycle of therapy. Fever and neutropenia were seen in 3.5% of patients. All Grades 3 and 4 non-hematologic toxicities were seen at a frequency of < 10%. Seventy women underwent SLO with a negative SLO rate of 53% with an additional 9% having microscopically positive procedures. Negative SLO rate was 74% in cohort 1 and 36% in cohort 2.Conclusions. Treatment with the modified triple doublet regimen is tolerable with an encouraging pathologic CR rate. (c) 2006 Elsevier Inc. All rights reserved.