Murren John R, Andersen Nicolaj, Psyrri Diamando, Brandt Deborah, Nadkarni Rajani, Rose Michal, Davies Marianne J, Parisot Nicole, Rosenfield Arthur T, Pizzorno Guiseppe, Zelterman Daniel
Yale University School of Medicine, New Haven, Connecticut 06520-8032, USA.
Cancer Biol Ther. 2005 Dec;4(12):1311-5. doi: 10.4161/cbt.4.12.2168. Epub 2005 Dec 12.
We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel in patients with advanced stage non-small cell lung cancer (NSCLC).
Patients were eligible if they had histologically confirmed chemotherapy naïve stage IV NSCLC or stage IIIB disease that was not suitable for combined modality therapy. Patients were treated with irinotecan 50 mg/m2 and paclitaxel 75 mg/m2 on days 1 and 8 of a 21-day cycle. If the patient did not experience >grade 1 toxicity during the first cycle, the dose of irinotecan could be escalated to 60 mg/m(2). Patients were evaluated for tumor response rate, time to progression (TTP), overall survival (OS) and toxicity.
Twenty-three eligible patients were treated. Two (9%) patients achieved a partial response. Eight patients (35%) had stable disease. The median number of cycles given per patient was four (range 1-29). The major toxicities were grade >or=3 neutropenia (26%) and grade 3 diarrhea (5%). The median time to progression was 2.8 months (range 0.5-21.8 months) for all patients and 4.3 months for the patients who had either stable disease or a partial response. The median overall survival was 9.2 months (range 0.5-40 months). The one- and two-year survival rates were 39% and 13%, respectively.
The combination of irinotecan and paclitaxel is safe in advanced NSCLC and affords a survival similar to other non-platinum as well as platinum-based doublets. However, this combination does not have sufficient activity to justify further study in an unselected population. If biomarkers are developed that can guide the selection of chemotherapy in an individual patient, there may be a rationale for further evaluation of this regimen.
我们开展了一项II期研究，以评估伊立替康与紫杉醇联合用药对晚期非小细胞肺癌（NSCLC）患者的疗效和安全性。
组织学确诊为未经化疗的IV期NSCLC或不适合综合治疗的IIIB期疾病患者符合入组条件。患者在21天周期的第１天和第8天接受伊立替康50mg/m²和紫杉醇75mg/m²治疗。如果患者在第一个周期中未出现>1级毒性反应，伊立替康剂量可增至60mg/m²。对患者进行肿瘤缓解率、疾病进展时间（TTP）、总生存期（OS）及毒性评估。
23例符合条件的患者接受了治疗。2例（9%）患者获得部分缓解。8例（35%）患者疾病稳定。每位患者接受的中位周期数为4个（范围1-29）。主要毒性反应为≥3级中性粒细胞减少（26%）和3级腹泻（5%）。所有患者的中位疾病进展时间为2.8个月（范围0.5-21.8个月），疾病稳定或部分缓解的患者为4.3个月。中位总生存期为9.2个月（范围0.5-40个月）。1年和2年生存率分别为39%和13%。
伊立替康与紫杉醇联合用药对晚期NSCLC患者安全，生存期与其他非铂类及铂类双联方案相似。然而，该联合方案活性不足，无法支持在未选择人群中开展进一步研究。如果能开发出可指导个体患者化疗选择的生物标志物，则可能有理由对该方案进行进一步评估。
