高剂量强度甲氨蝶呤、长春碱、阿霉素和顺铂（MVAC）化疗联合重组人粒细胞集落刺激因子与经典MVAC方案治疗晚期尿路上皮肿瘤的随机III期试验：欧洲癌症研究与治疗组织第30924号方案

Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924.

作者信息

Sternberg C N, de Mulder P H, Schornagel J H, Théodore C, Fossa S D, van Oosterom A T, Witjes F, Spina M, van Groeningen C J, de Balincourt C, Collette L

机构信息

Vincenzo Pansadoro Foundation, Rome, Italy.

出版信息

J Clin Oncol. 2001 May 15;19(10):2638-46. doi: 10.1200/JCO.2001.19.10.2638.

DOI:10.1200/JCO.2001.19.10.2638

PMID:11352955

Abstract

PURPOSE

This randomized trial evaluated antitumor activity of and survival asociated with high-dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC).

PATIENTS AND METHODS

A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles).

RESULTS

Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was.009; and for the overall response, it was.06. There was no statistically significant difference in survival (P =.122) or time to progression (P =.114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio.75; 95% CI.58 to.98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%).

CONCLUSION

With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

摘要

目的

本随机试验评估了高剂量强度化疗（甲氨蝶呤、长春花碱、阿霉素和顺铂[MVAC]加粒细胞集落刺激因子[HD-MVAC]）与MVAC相比，对晚期移行细胞癌（TCC）患者的抗肿瘤活性及生存情况。

患者与方法

共有263例未曾接受过化疗的转移性或晚期TCC患者被随机分为HD-MVAC组（2周周期）或MVAC组（4周周期）。

结果

采用意向性分析，在中位随访38个月时，HD-MVAC组有28例完全缓解（CR）（21%）和55例部分缓解（PR）（41%），总缓解率为62%（95%置信区间[CI]，54%至70%）。MVAC组有12例CR（9%）和53例PR（41%），总缓解率为50%（95%CI，42%至59%）。CR率差异的P值为0.009；总缓解率差异的P值为0.06。生存情况（P = 0.122）或疾病进展时间（P = 0.114）无统计学显著差异。HD-MVAC组的无进展生存期显著更好（P = 0.037；风险比0.75；95%CI 0.58至0.98）。HD-MVAC组的中位无进展生存时间为9.1个月，MVAC组为8.2个月。HD-MVAC组的2年无进展生存率为24.7%（95%CI，17.1%至32.3%），MVAC组为11.6%（95%CI，5.9%至17.4%）。