多中心2期研究：新辅助紫杉醇、磷酸雌莫司汀和卡铂联合雄激素剥夺疗法用于高危局限性前列腺癌患者放疗前的治疗——癌症与白血病B组99811研究结果

Multicenter phase 2 study of neoadjuvant paclitaxel, estramustine phosphate, and carboplatin plus androgen deprivation before radiation therapy in patients with unfavorable-risk localized prostate cancer: results of Cancer and Leukemia Group B 99811.

作者信息

Kelly William Kevin, Halabi Susan, Elfiky Aymen, Ou San-San, Bogart Jeff, Zelefsky Michael, Small Eric

机构信息

Department of Medicine, Yale University, New Haven, Connecticut 06520, USA.

出版信息

Cancer. 2008 Dec 1;113(11):3137-45. doi: 10.1002/cncr.23910.

DOI:10.1002/cncr.23910

PMID:18989865

Abstract

BACKGROUND

A multicenter phase 2 trial was conducted to evaluate the safety and feasibility of radiotherapy after paclitaxel, estramustine phosphate, and carboplatin (TEC) plus androgen deprivation therapy in previously untreated unfavorable-risk localized prostate cancer patients.

METHODS

Patients with localized high-risk prostate cancer were treated with 4 cycles (16 weeks) of continuous weekly paclitaxel at 80 mg/m(2) intravenously with estramustine at 280 mg orally 3 times a day for 5 days a week and carboplatin (area under the curve of 6) on Day 1 of every cycle followed by 3-dimensional conformal or intensity-modulated radiotherapy (total dose of 77.4 gray [Gy] in 1.8-Gy fractions). All patients received androgen deprivation therapy with either goserelin acetate at 3.6 mg subcutaneously or leuprolide acetate at 7.5 mg intramuscularly monthly for 6 months starting at Day 1 of therapy. Patients were evaluated for acute and late toxicities along with progression-free survival and time to prostate-specific antigen (PSA) failure associated with the multimodality therapy.

RESULTS

Twenty-seven of 34 patients completed therapy and were evaluable for safety and feasibility. There was 1 patient with grade 3 nausea during chemotherapy. No other grade 3 or 4 gastrointestinal, cardiovascular, or genitourinary acute or late toxicities were reported. The most common grade 1 to 2 late toxicities were proctitis (11%), dysuria (11%), and urinary frequency/urgency (33%). Two deaths due to prostate cancer were observed. Median follow-up was 38 months among 24 surviving patients; median PSA progression-free survival was 12.1 months (95% confidence interval, 13.3-25.9).

CONCLUSIONS

Neoadjuvant chemohormonal therapy with TEC followed by high-dose radiation therapy is safe and feasible in a multicenter setting.

摘要

背景

开展了一项多中心2期试验，以评估紫杉醇、磷酸雌莫司汀和卡铂（TEC）联合雄激素剥夺治疗后，对既往未接受过治疗的高危局限性前列腺癌患者进行放射治疗的安全性和可行性。

方法

局限性高危前列腺癌患者接受4个周期（16周）的治疗，每周持续静脉注射紫杉醇80mg/m²，同时口服磷酸雌莫司汀280mg，每天3次，每周5天，每个周期第1天给予卡铂（曲线下面积为6），随后进行三维适形或调强放射治疗（总剂量77.4格雷[Gy]，每次分割剂量1.8Gy）。所有患者从治疗第1天开始接受雄激素剥夺治疗，皮下注射醋酸戈舍瑞林3.6mg或每月肌肉注射醋酸亮丙瑞林7.5mg，持续6个月。对患者进行急性和晚期毒性评估，以及与多模式治疗相关的无进展生存期和前列腺特异性抗原（PSA）失败时间评估。

结果

34例患者中有27例完成治疗，可进行安全性和可行性评估。化疗期间有1例患者出现3级恶心。未报告其他3级或4级胃肠道、心血管或泌尿生殖系统急性或晚期毒性。最常见的1至2级晚期毒性是直肠炎（11%）、排尿困难（11%）和尿频/尿急（33%）。观察到2例因前列腺癌死亡。24例存活患者的中位随访时间为38个月；中位PSA无进展生存期为12.1个月（95%置信区间，13.3 - 25.9）。