拓扑替康和顺铂联合每日两次同步放化疗治疗局限期小细胞肺癌——丹麦肺癌肿瘤学组（DOLG）II期试验

Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group (DOLG) phase II trial.

作者信息

Sorensen Morten, Lassen Ulrik, Palshof Torben, Jensen Britta Bjerregaard, Johansen Jørgen, Jensen Peter Buhl, Langer Seppo W

机构信息

Department of Oncology, 5073, The Finsen Centre, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

出版信息

Lung Cancer. 2008 May;60(2):252-8. doi: 10.1016/j.lungcan.2007.09.022. Epub 2007 Nov 26.

DOI:10.1016/j.lungcan.2007.09.022

PMID:18036701

Abstract

INTRODUCTION

The longest survival time reported in randomised trials of limited disease (LD) SCLC has been achieved with early twice-daily concurrent chemoradiation. Topotecan is active in recurrent SCLC and in extensive disease as first line treatment.

AIM

To incorporate and assess the effect of topotecan with concurrent twice-daily radiochemotherapy in LD SCLC.

PATIENT AND METHODS

Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1; vincristine, 1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days. Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) < or =2. Pts older than 64 years with PS=2 and LDH>two times the upper limit were excluded.

RESULT

Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43-75. PS was < or =1 in 90% of pts. Non-haematological toxicity was mild except grade 3 esophagitis, which was observed in 26.5% of pts. One pt developed an esophageal stricture. Grade 3/4 leucopenia and thrombocytopenia were observed in 82.5% and 75.0 of pts, respectively. One patient died due to neutropenic sepsis. The overall response rate was 77.5% with 30.0% achieving a complete response. Median progression-free survival was 11.8 months (95% CI: 1.3-22.2). Median overall survival was 22.9 months (95% CI: 13.4-31.5) and 5-year survival was 21%.

CONCLUSION

The combination of topotecan and cisplatin with concurrent twice-daily chemoradiation results in long-term survivors. As expected the incidence of severe esophagitis is high.

摘要

引言

在局限性疾病（LD）小细胞肺癌（SCLC）的随机试验中，报道的最长生存时间是通过早期每日两次同步放化疗实现的。拓扑替康在复发性SCLC和广泛期疾病的一线治疗中具有活性。

目的

纳入并评估拓扑替康联合每日两次同步放化疗在LD SCLC中的效果。

患者与方法

一项多中心II期研究，采用方案A（拓扑替康静脉注射，1.5mg/m²，第1 - 5天；顺铂50mg/m²，第1天）三个周期和方案B（依托泊苷静脉注射，120mg/m²，第1 - 3天；卡铂，AUC = 5，第1天；长春新碱，1.3mg/m²，第1天）三个周期，按以下顺序给药：每21天A - B - B - A - B - A。每日两次放疗（1.5Gy×30，每周10次分割，共45Gy）与第一个周期B同步进行。对完全缓解的患者提供预防性脑照射。符合条件的患者为未经SCLC治疗、器官功能良好且世界卫生组织（WHO）体能状态（PS）≤2的LD SCLC患者。排除年龄大于64岁、PS = 2且乳酸脱氢酶（LDH）高于上限两倍的患者。

结果

四个中心共纳入45例患者。5例患者不符合纳入标准。符合条件患者的中位年龄为60岁，范围43 - 75岁。90%的患者PS≤1。除3级食管炎外，非血液学毒性较轻，26.5%的患者出现3级食管炎。1例患者发生食管狭窄。82.5%和75.0%的患者分别出现3/4级白细胞减少和血小板减少。1例患者死于中性粒细胞减少性败血症。总缓解率为77.5%，30.0%的患者达到完全缓解。中位无进展生存期为11.8个月（95%可信区间：1.3 - 22.2）。中位总生存期为22.9个月（95%可信区间：13.4 - 31.5），5年生存率为21%。