Oncology Coordination Centre, Grenoble University Hospital, Grenoble, France.
Lung Cancer. 2012 Oct;78(1):112-20. doi: 10.1016/j.lungcan.2012.06.006. Epub 2012 Jul 12.
Standard treatment of small-cell lung cancer (SCLC) is a combination of etoposide and platinum for patients with extensive disease, associated with radiotherapy for patients with limited disease (LD). Therapeutic strategies for relapse, although well characterized, are disappointing. Between 1997 and 2009, 300 patients were treated for SCLC at Grenoble University Hospital. We analyzed patients' characteristics and outcomes at different treatment steps, to determine prognostic factors and propose subsequent treatment strategies according to "sensitive", "resistant" or "refractory" status established after first-line treatment (L1). The median patient age was 63.2 years, 46.3% had LD, and 23% were female. The objective response rate (ORR) to first-line chemotherapy was 73% [CI(95%): 67.6-77.9] and median survival was 13 months. After L1, comparison between "refractory" and "sensitive" groups showed more extensive disease (76.6% vs. 34.3%, p=0.003), poorer Performance Status (PS 0-1: 48.4% vs. 67.8%, p=0.008), more endocrine paraneoplastic syndrome (18.7% vs. 8.4%, p=0.03) and more composite histology (17.2% vs. 4.9%, p=0.004) in "refractory" patients. After second line (L2), ORR was 55.8% [CI(95%): 45.2-66.0] in "sensitive", 18.2% [CI(95%): 8.2-32.7] in "resistant", and 14.7% [CI(95%): 4.9-31.0] in "refractory" groups; with partial response only for the last two groups. After L3 and L4, ORR was 24.0% [CI(95%): 14.9-35.2] in "sensitive", 9.1% [CI(95%): 11.2-29.2] in "resistant" with partial response only. No response was observed for "refractory". After L1, the median survival was respectively 23, 10 and 6.4 months for "sensitive", "resistant" and "refractory" groups (p<0.001). Multivariate analysis showed that LD and classical SCLC histology were positive predictors of belonging to the "sensitive" group. Positive factors for survival were sensitivity to L1, PS 0-1, LD, Charlson score <4, no endocrine paraneoplastic syndrome and no occupational exposure. Limited disease is the major predictive factor for sensitivity to treatments and survival. Factors linked to the patients' clinical presentation also impact on survival. With currently recommended drugs, the "sensitivity" of the patient determined by the response to L1 indicates that it is pointless to treat "sensitive" with L4, "resistant" with L3 and "refractory" with L2, except for a few selected patients after multidisciplinary group discussion.
小细胞肺癌（SCLC）的标准治疗是依托泊苷和铂类药物联合治疗广泛期疾病，并联合放疗治疗局限期疾病（LD）患者。尽管复发的治疗策略已经得到很好的描述，但结果仍令人失望。1997 年至 2009 年间，格勒诺布尔大学医院共治疗了 300 例 SCLC 患者。我们分析了不同治疗阶段患者的特征和结局，以确定预后因素，并根据一线治疗（L1）后确定的“敏感”、“耐药”或“难治”状态，提出后续治疗策略。患者的中位年龄为 63.2 岁，46.3%为 LD，23%为女性。一线化疗的客观缓解率（ORR）为 73%[95%置信区间（CI）：77.9-67.6]，中位总生存期为 13 个月。在 L1 后，“难治”和“敏感”组之间的比较显示，“难治”组疾病更广泛（76.6% vs. 34.3%，p=0.003），表现状态（PS 0-1）更差（48.4% vs. 67.8%，p=0.008），内分泌副肿瘤综合征更常见（18.7% vs. 8.4%，p=0.03），复合组织学更常见（17.2% vs. 4.9%，p=0.004）。二线治疗（L2）后，“敏感”组的 ORR 为 55.8%[95%CI：45.2-66.0]，“耐药”组为 18.2%[95%CI：8.2-32.7]，“难治”组为 14.7%[95%CI：4.9-31.0]；只有后两组出现部分缓解。三线治疗（L3）和四线治疗（L4）后，“敏感”组的 ORR 为 24.0%[95%CI：14.9-35.2]，“耐药”组为 9.1%[95%CI：11.2-29.2]，只有部分缓解。“难治”组没有反应。在 L1 后，“敏感”、“耐药”和“难治”组的中位总生存期分别为 23、10 和 6.4 个月（p<0.001）。多变量分析显示，LD 和经典小细胞肺癌组织学是属于“敏感”组的阳性预测因子。与生存相关的积极因素包括对 L1 的敏感性、PS 0-1、LD、Charlson 评分<4、无内分泌副肿瘤综合征和无职业暴露。LD 是对治疗和生存敏感的主要预测因素。与患者临床表现相关的因素也会影响生存。在目前推荐的药物治疗中，患者对 L1 的“敏感性”表明，对于“敏感”患者，进行 L4 治疗、“耐药”患者进行 L3 治疗、“难治”患者进行 L2 治疗是没有意义的，除非经过多学科小组讨论后选择了少数患者。
