Background and objective: Small-cell lung cancer (SCLC) is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress after the first-line therapy. The evidence of a benefit from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the efficacy and safety of different second-line treatment regimens.
Methods: We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC), and the rest 152 patients received second-line chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. The endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Results: Patients administered second-line chemotherapy lived significantly longer, with a total OS from first-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001), and the ORR, DCR, PFS and OS of the former (including the sensitive disease and resistance/refractory disease patients) were obviously better than that of the latter. The ORR and DCR of the patients who received second-line chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second-line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line chemotherapy were divided by types of second-line regimens. The sensitive disease patients were from group A (VP-16-based rechallenge) and group B1 (CPT-11-based regimen). The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6% and 58.8%, respectively. There was no statistically significant difference (P=0.264; P=0.400). The median PFS from second-line chemotherapy of the two groups were 4.0 mo and 3.0 mo, and the second-line median OS were 6.5 mo and 4.5 mo. There was no statistic difference (P=0.432; P=0.508). The resistance/refractory disease patients were divided into group B2 (CPT-11-based regimen), group C (PTX/DXL-based regimen) and group D (TPT-based regimen). There was no statistic difference in second-line ORR, DCR and median PFS among the three groups (P value is 0.521, 0.528 and 0.775, respectively); The median OS from second-line chemotherapy of the group D is longer than that of group B2 and group C, with statistical difference (P=0.043; P=0.030). The differences of grade III-IV hematologic toxicities among the four subgroups were not statistically different. The incidence of diarrhea in non-hematologic toxicities in patients who received irinotecan as second-line chemotherapy was higher than other three subgroups (P=0.029).
Conclusions: Patients who progressed after the completion of first-line chemotherapy can gain survival benefit. The response and the PFS of the different second-line chemotherapies were similar. The patients who received the TPT-based regimen may gain longer overall survival than other resistance/refractory disease patients. .
背景与目的 小细胞肺癌是一种侵袭性非常强的肿瘤，其主要治疗方案是细胞毒化疗，尽管有较高的初始治疗缓解率，但大部分患者在一线治疗后会出现复发或进展。目前只有较少的证据证明二线治疗能给复发或晚期小细胞肺癌患者带来生存获益，指南推荐药物较多，但临床多依据经验制定方案。本研究回顾性分析小细胞肺癌患者不同二线治疗方案的疗效和安全性，以指导临床医生更客观地选择小细胞肺癌二线治疗方案。方法 回顾性分析了309例接受二线治疗的小细胞肺癌患者，其中157例患者进展后仅予最佳支持治疗，其余152例患者进行了二线化疗。采用Kaplan-Meier法生存曲线及Log-rank检验等统计学方法，观察终点为客观缓解率（objective response rate, ORR）、疾病控制率（disease control rate, DCR）、无进展生存时间（progression-free survival, PFS）、总生存时间（overall survival, OS）和安全性分析。结果 接受二线化疗的患者较二线仅接受最佳支持治疗的患者生存获益明显，两组患者自一线治疗开始的OS分别为11.5个月和6.0个月（P<0.001），并且前者无论何种复发类型，在二线治疗ORR、DCR、PFS和OS上均明显优于后者。接受二线化疗患者，其ORR为39.5%，DCR为59.2%，中位PFS和中位OS分别为3.3个月和5.3个月。据方案将二线化疗患者分组，敏感型复发患者由采用含VP-16方案的A组和采用含CPT-11方案的B1组组成，两组ORR分别为48.6%和35.3%，DCR分别为68.6%和58.8%，均无明显差异（P值分别为0.264和0.400）；两组二线中位PFS分别为4.0个月和3.0个月，无明显差异（P=0.432）；两组中位OS分别为6.5个月和4.5个月，无统计学差异（P=0.508）。耐药/难治型复发患者由其余含CPT-11方案的B2组、含PTX/DXL方案的C组和含TPT方案的D组组成。组间ORR、DCR、二线中位PFS无明显统计学差异（P值分别为0.521、0.528和0.775）；D组中位OS优于B2组和C组，差异具有统计学意义（P值分别为0.043、0.030）。四个方案组毒副作用相似，III度-IV度血液学毒性组间并无差异；伊立替康组的患者腹泻发生率高于其他三组（P=0.029）。结论 二线化疗可以给一线治疗失败的小细胞肺癌患者带来生存获益；不同二线化疗方案患者的近期缓解和无进展生存相似；耐药/难治型患者二线化疗采用含TPT的方案可能会给患者带来更好的总生存获益。.