Vaishampayan Ulka, Fontana Joseph, Du Wei, Hussain Maha
Division of Hematology/Oncology, Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine, Detroit, Michigan, USA.
Urology. 2002 Dec;60(6):1050-4. doi: 10.1016/s0090-4295(02)01990-8.
The efficacy of weekly high-dose paclitaxel in androgen-independent prostate carcinoma and its cytotoxic synergy with estramustine led to the evaluation of a weekly schedule of paclitaxel and estramustine in this Phase II trial.
Patients were eligible if they had metastatic prostate adenocarcinoma with objective progression or rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy and antiandrogen withdrawal. Prior radiation and/or one prior chemotherapy regimen was permitted. A Zubrod performance status of 2 or less and adequate bone marrow and hepatic and renal function were required. Estramustine was administered orally at a dose of 280 mg three times daily on days 1 to 3, 8 to 10, and 15 to 17. Paclitaxel (150 mg/m2) was administered as a 1-hour intravenous infusion on days 2, 9, and 16. Therapy was repeated every 28 days (one cycle).
Twenty-eight patients were enrolled (median age 71.5 years). Fifteen patients had measurable disease (nine nodal and seven visceral) and 13 had bone-only metastases. A total of 116 cycles of therapy were delivered (median 4 cycles per patient, range 1 to 12). Nine patients required dose reduction. The predominant toxicities consisted of grade 3 neuropathy in 6 patients and grade 3 and 4 neutropenia in 4 patients, with one hospitalization for febrile neutropenia. Three patients had thrombotic manifestations: one deep venous thrombosis and two non-Q wave myocardial infarctions. Of the 28 patients, 26 were assessable for response. Of 13 patients with measurable disease, 5 demonstrated a partial response (1 in the liver and 4 in the lymph nodes), and 8 of 13 patients with bone-only metastases had a 50% or greater decrease in PSA level. Three patients had a 90% or greater decline in PSA. The overall PSA response rate was 61.53% (95% confidence interval 38.1% to 74.2%). The median time to progression was 4.64 months, and the median survival was 13 months.
The combination of weekly estramustine and paclitaxel is active in metastatic androgen-independent prostate cancer.
每周一次高剂量紫杉醇治疗雄激素非依赖性前列腺癌的疗效及其与雌莫司汀的细胞毒性协同作用，促使在这项II期试验中对紫杉醇和雌莫司汀的每周给药方案进行评估。
若患者患有转移性前列腺腺癌，尽管接受了雄激素剥夺治疗和抗雄激素撤药，但仍有客观进展或前列腺特异性抗原（PSA）水平升高，则符合入组条件。允许既往接受过放疗和/或一种既往化疗方案。要求Zubrod体能状态为2或更低，且骨髓、肝肾功能良好。在第1至3天、第8至10天和第15至17天，雌莫司汀口服给药，剂量为280 mg，每日3次。紫杉醇（150 mg/m²）在第2天、第9天和第16天静脉输注1小时。每28天重复一次治疗（一个周期）。
入组28例患者（中位年龄71.5岁）。15例患者有可测量病灶（9例为淋巴结转移，7例为内脏转移），13例仅有骨转移。共进行了116个周期的治疗（每位患者中位4个周期，范围1至12个周期）。9例患者需要减量。主要毒性包括6例3级神经病变和4例3级及4级中性粒细胞减少，1例因发热性中性粒细胞减少住院。3例患者有血栓形成表现：1例深静脉血栓形成和2例非Q波心肌梗死。28例患者中，26例可评估疗效。13例有可测量病灶的患者中，5例出现部分缓解（1例肝脏转移，4例淋巴结转移），13例仅有骨转移的患者中，8例PSA水平下降50%或更多。3例患者PSA下降90%或更多。总体PSA缓解率为61.53%（95%置信区间38.1%至74.2%）。中位进展时间为4.64个月，中位生存期为13个月。
每周一次雌莫司汀和紫杉醇联合方案对转移性雄激素非依赖性前列腺癌有效。
