紫杉醇+BEP（T-BEP）方案作为预后不良的非精原细胞瘤生殖细胞肿瘤患者的诱导化疗：一项 II 期研究。

Paclitaxel+BEP (T-BEP) regimen as induction chemotherapy in poor prognosis patients with nonseminomatous germ cell tumors: a phase II study.

机构信息

Department of Clinical Pharmacology and Chemotherapy, NN Blokhin Russian Cancer Research Center, Moscow, Russia.

出版信息

Urology. 2011 Sep;78(3):620-5. doi: 10.1016/j.urology.2011.05.005. Epub 2011 Jul 20.

DOI:10.1016/j.urology.2011.05.005

PMID:21764427

Abstract

OBJECTIVES

To evaluate paclitaxel, bleomycin, etoposide, and cisplatin (T-BEP) in patients with poor-prognosis nonseminomatous germ cell tumor (NSGCT). Paclitaxel is an active treatment of nonseminomatous germ cell tumors.

METHODS

The present study was an open-label, single-center, Phase II study. Chemotherapy-naive patients received T-BEP (paclitaxel 175 mg/m2 [day 2], cisplatin 20 mg/m2 [days 1-5], etoposide 100 mg/m2 [days 1-5], bleomycin 30 IU [days 1, 3, and 5]), and granulocyte colony-stimulating factor 300 μg (days 6-10). The number of cycles (range 4-6) was dependent on the normalization of tumor markers. Secondary resection was planned for patients with tumor marker-negative partial remission. Assessments included radiologic response, tumor markers, and safety. The primary endpoint was progression-free survival (PFS) 1 year after chemotherapy.

RESULTS

Of 51 patients, 49 completed chemotherapy and were evaluable for response: 12 (25%) had a complete response, 29 (59%) were marker-negative (tumor marker normalization) and 3 (6%) were marker-positive (tumor marker decrease for ≥1 month) incomplete responders, and 5 (10%) had progressive disease. A total of 37 patients underwent secondary resection. After the treatment of 27 patients, an unplanned analysis showed inappropriate toxicity at cycle 1 (grade 3-4 infection [6 patients] resulting in 2 toxic deaths), which led to treatment modification (BEP [cycle 1], T-BEP [subsequent cycles]), with no further toxic deaths observed. Grade 3-4 adverse events included neutropenia (71%), febrile neutropenia (33%), and infection (14%). During the first year after chemotherapy, 1 patient was lost to follow-up, and 21 patients relapsed. The PFS rate at 1 year after chemotherapy was 58% (29 of 50 patients).

CONCLUSIONS

T-BEP did not improve PFS in patients with poor-prognosis NSGCT. The administration of T-BEP from cycle 1 resulted in excessive toxicity but was administered safely from cycle 2.

摘要

目的

评估紫杉醇、博来霉素、依托泊苷和顺铂（T-BEP）在预后不良的非精原细胞瘤生殖细胞肿瘤（NSGCT）患者中的疗效。紫杉醇是一种非精原细胞瘤生殖细胞肿瘤的有效治疗药物。

方法

本研究为单中心、开放性、Ⅱ期研究。化疗初治患者接受 T-BEP（紫杉醇 175mg/m2[第 2 天]，顺铂 20mg/m2[第 1-5 天]，依托泊苷 100mg/m2[第 1-5 天]，博来霉素 30IU[第 1、3 和 5 天]）和粒细胞集落刺激因子 300μg（第 6-10 天）治疗。周期数（范围 4-6）取决于肿瘤标志物的正常化。对于肿瘤标志物阴性部分缓解的患者计划进行二次切除术。评估包括影像学反应、肿瘤标志物和安全性。主要终点是化疗后 1 年无进展生存期（PFS）。

结果

51 例患者中，49 例完成化疗并可评估疗效：12 例（25%）完全缓解，29 例（59%）肿瘤标志物阴性（肿瘤标志物正常化），3 例（6%）肿瘤标志物阳性（肿瘤标志物下降≥1 个月）不完全缓解，5 例（10%）疾病进展。共 37 例患者进行了二次切除术。在 27 例患者的治疗后，一项计划外分析显示第 1 周期出现不适当毒性（3 级-4 级感染[6 例]导致 2 例毒性死亡），导致治疗方式改变（BEP[第 1 周期]，T-BEP[后续周期]），未再观察到毒性死亡。3 级-4 级不良事件包括中性粒细胞减少症（71%）、发热性中性粒细胞减少症（33%）和感染（14%）。化疗后 1 年内，1 例患者失访，21 例患者复发。化疗后 1 年的 PFS 率为 58%（50 例患者中的 29 例）。