广泛期小细胞肺癌患者顺铂-依托泊苷序贯给药后再用拓扑替康治疗。一项多中心II期研究。

Sequential administration of cisplatin-etoposide followed by topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II study.

作者信息

Mavroudis D, Pavlakou G, Blazoyiannakis G, Veslemes M, Apostolopoulou F, Kouroussis Ch, Kakolyris S, Agelaki S, Androulakis N, Vardakis N, Magkanas E, Samonis G, Georgoulias V

机构信息

Department of Medical Oncology, School of Medicine, University of Crete, University General Hospital of Heraklion, PO Box 1352, Heraklion, Crete 71110, Greece.

出版信息

Lung Cancer. 2003 Jan;39(1):71-6. doi: 10.1016/s0169-5002(02)00307-0.

DOI:10.1016/s0169-5002(02)00307-0

PMID:12499097

Abstract

PURPOSE

To evaluate the activity of the sequential administration of cisplatin-etoposide (PE) followed by topotecan (TOP) in patients with extensive stage small cell lung cancer (SCLC).

PATIENTS AND METHODS

Previously untreated patients with extensive stage SCLC received 4 cycles of cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 every 21 days followed by 4 cycles of TOP 1.5 mg/m(2) IV on days 1-5 every 21 days.

RESULTS

Thirty-eight patients were entered in the study. Their median age was 63 years and the performance status (WHO) was 0 for 5, 1 for 25 and 2 for 8 patients. All patients were evaluable for toxicity and 32 for response to PE and 25 to TOP. Of the 38 patients receiving PE, 1 (3%) patient achieved complete response (CR) and 17 (45%) partial responses (PR) for an overall response rate to PE of 47% (95% confidence interval: 36.7-68.5%). Four (23.5%) of the 17 patients with PR after PE, achieved CR with TOP. None of the patients with stable or progressive disease after PE responded to TOP. The response rate of the 27 patients receiving TOP following PE was 15% (95% confidence interval: 1.4-28.2%). After a median follow up of 9 months, the median duration of response was 6.5 months, the time to tumor progression 6.5 months, the median survival 8.5 months and the 1-year survival 34%. A total of 136 cycles of PE and 89 cycles of TOP have been administered with a median of 4 cycles/patient for each regimen. There were 2 toxic deaths after PE associated with grade IV febrile neutropenia. Treatment delays due to toxicity occurred in 17 (12%) cycles of PE and 20 (22%) cycles of TOP while doses were reduced in 7 (5%) and 4 (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia occurred in 24, 2 and 3% of PE cycles and 21, 12 and 1% of TOP. Non-hematologic toxicity was mild. The delivered dose intensity was 100% for PE and 93% for TOP.

CONCLUSIONS

The sequential administration of TOP after PE is associated with manageable toxicity and may increase the number of CRs in patients with chemosensitive extensive stage SCLC. However, based on this data and the lack of survival benefit in a previous phase III study, the sequential regimen should not be used outside of a clinical trial.

摘要

目的

评估顺铂 - 依托泊苷（PE）序贯拓扑替康（TOP）方案治疗广泛期小细胞肺癌（SCLC）患者的疗效。

患者与方法

既往未接受过治疗的广泛期SCLC患者每21天接受4个周期的治疗，第1天静脉注射顺铂75mg/m²，第1 - 3天静脉注射依托泊苷100mg/m²，随后每21天接受4个周期的治疗，第1 - 5天静脉注射拓扑替康1.5mg/m²。

结果

38例患者进入本研究。他们的中位年龄为63岁，体力状况（WHO）评分为0分的有5例，1分的有25例，2分的有8例。所有患者均可评估毒性，32例可评估对PE的反应，25例可评估对TOP的反应。在接受PE治疗的38例患者中，1例（3%）达到完全缓解（CR），17例（45%）部分缓解（PR），PE的总缓解率为47%（95%置信区间：36.7 - 68.5%）。PE治疗后达到PR的17例患者中有4例（23.5%）接受TOP治疗后达到CR。PE治疗后病情稳定或进展的患者对TOP均无反应。PE治疗后接受TOP治疗的27例患者的缓解率为15%（95%置信区间：1.4 - 28.2%）。中位随访9个月后，中位缓解持续时间为6.5个月，肿瘤进展时间为6.5个月，中位生存期为8.5个月，1年生存率为34%。共给予136个周期的PE和89个周期的TOP，每个方案的中位治疗周期数为4个周期/患者。PE治疗后有2例因毒性导致的死亡，与IV级发热性中性粒细胞减少有关。因毒性导致的治疗延迟在PE治疗周期中有17例（12%），TOP治疗周期中有20例（22%），而分别有7例（5%）和4例（4%）周期的剂量减少。3 - 4级中性粒细胞减少、血小板减少和发热性中性粒细胞减少在PE治疗周期中分别发生24%、2%和3%，在TOP治疗周期中分别发生21%、12%和%。非血液学毒性较轻。PE的给药剂量强度为100%，TOP为93%。