多中心随机临床试验：高剂量表柔比星联合顺铂对比长春瑞滨联合顺铂治疗晚期非小细胞肺癌

Multicenter randomized clinical trial on high-dose epirubicin plus cis-platinum versus vinorelbine plus cis-platinum in advanced non small cell lung cancer.

作者信息

Martoni A, Guaraldi M, Piana E, Strocchi E, Petralia A, Busutti L, Preti P, Robustelli G, Raimondi M, Ferrara G, Palomba G, Lelli G, Picece V, Recaldin E, Caffo O, Ambrosini G, Sarobba G, Farris A, Pannuti F

机构信息

Division of Medical Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy.

出版信息

Lung Cancer. 1998 Oct;22(1):31-8. doi: 10.1016/s0169-5002(98)00065-8.

DOI:10.1016/s0169-5002(98)00065-8

PMID:9869105

Abstract

BACKGROUND

High dose Epirubicin (HD-EPI) (>90 mg/m2) and Vinorelbine (VNR) demonstrated antitumor activity as single agent (about 20%) in the treatment of advanced NSCLC. This trial compares these two agents combined with cisplatin (CP).

PATIENTS AND METHODS

From August 1992 to February 1996, 228 patients with locally advanced or metastatic NSCLC were randomized to receive either EPI 120 mg/m2 as i.v. bolus plus Cisplatin (CP) 60 mg/m2 on day 1 (regimen A) or VNR 25 mg/m2 as i.v. bolus on day 1 and 8 plus CP 60 mg/m2 on day 1 (regimen B). Both treatments were recycled every 21 days up to a maximum cumulative dose of EPI of 840 mg/m2 or 12 cycles. Eligible patients were 212 and 198 patients were evaluable for objective response (95 in arm A and 103 in arm B). The main characteristics of eligible patients were: male/female 179/33; median age 61 (42-72); median Karnofsky PS 80 (70-100); stage IIIA 12%, stage IIIB 40%, stage IV 41%, recurrence 7%; histotype: epidermoid 48%, adenoca 36%, others 16%.

RESULTS

The following response rates were observed in regimens A and B, respectively; CR, 1 and 2%, PR, 32 and 25% (P = 0.4567). Median CR + PR duration was 9 and 8 months, respectively. Median survival was 10.5 and 9.6 months, respectively. Grade III-IV leucopenia occurred in 38 and 21% in arm A and arm B, respectively(P = 0.01), thrombocytopenia in 6 and 0% (P = 0.02), anemia in 8 and 7% (n.s.). Non-hematological toxicity was moderate and the only difference between the treatments was alopecia (88 vs. 33% in arm A and B, respectively). Supraventricular arrhythmia occurred in three patients on regimen A; a >15% LVEF absolute decrease was observed in 9 (22.5%) and three (14%) patients on arm A and arm B, respectively (n.s.). No congestive heart failure was observed.

CONCLUSION

HD-EPI+CP and VNR+CP are both active combinations in advanced NSCLC with a similar response rate, response duration and survival but regimen A was significantly more toxic (myelosuppression and alopecia).

摘要

背景

高剂量表柔比星（HD-EPI）（>90mg/m²）和长春瑞滨（VNR）作为单药在晚期非小细胞肺癌（NSCLC）治疗中显示出抗肿瘤活性（约20%）。本试验比较这两种药物与顺铂（CP）联合应用的效果。

患者与方法

1992年8月至1996年2月，228例局部晚期或转移性NSCLC患者被随机分为两组，一组在第1天接受静脉推注表柔比星120mg/m²加顺铂60mg/m²（方案A），另一组在第1天和第8天接受静脉推注长春瑞滨25mg/m²加第1天顺铂60mg/m²（方案B）。两种治疗均每21天重复一次，表柔比星的最大累积剂量为840mg/m²或最多12个周期。符合条件的患者有212例，198例患者可评估客观缓解情况（A组95例，B组103例）。符合条件患者的主要特征为：男/女179/33；中位年龄61岁（42 - 72岁）；中位卡氏评分80分（70 - 100分）；ⅢA期12%，ⅢB期40%，Ⅳ期41%，复发7%；组织学类型：鳞状细胞癌48%，腺癌36%，其他16%。

结果

方案A和方案B分别观察到以下缓解率；完全缓解（CR），分别为1%和2%，部分缓解（PR），分别为32%和25%（P = 0.4567）。CR + PR的中位持续时间分别为9个月和8个月。中位生存期分别为10.5个月和9.6个月。A组和B组Ⅲ - Ⅳ级白细胞减少分别发生在38%和21%（P = 0.01），血小板减少分别为6%和0%（P = 0.02），贫血分别为8%和7%（无统计学差异）。非血液学毒性为中度，两种治疗之间唯一的差异是脱发（A组和B组分别为88%和33%）。方案A有3例患者发生室上性心律失常；A组和B组分别有9例（22.5%）和3例（14%）患者观察到左心室射血分数（LVEF）绝对下降>15%（无统计学差异）。未观察到充血性心力衰竭。