治疗方案因肿瘤分期而异。[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: small cell lung cancer. 2016. http://www.nccn.org (last accessed 30 August 2016).http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
在患者评估的过程中涉及许多变量和综合因素。患者应该在肿瘤专科中心内接受多学科的综合治疗。
局限性疾病
局限期 SCLC 患者同时接受化疗和放射治疗 (RT)。[39]Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992;327:1618-1624.http://www.ncbi.nlm.nih.gov/pubmed/1331787?tool=bestpractice.com化疗主要包括顺铂和依托泊苷,有时卡铂可用来代替顺铂。推荐接受同步放疗。[39]Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992;327:1618-1624.http://www.ncbi.nlm.nih.gov/pubmed/1331787?tool=bestpractice.com死亡率减低:有高质量证据表明,胸部放疗加上化疗比单纯化疗在减低局限期 SCLC 患者 3 年死亡率上更为有效。[39]Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992;327:1618-1624.http://www.ncbi.nlm.nih.gov/pubmed/1331787?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。早期放疗(在第 1/2 周期化疗进行)优于在化疗周期后期进行放疗。[40]Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol. 2004;22:4837-4845.http://www.ncbi.nlm.nih.gov/pubmed/15570087?tool=bestpractice.com死亡率减低:有一定证据,表明早期放疗比晚期放疗更为有效。[40]Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol. 2004;22:4837-4845.http://www.ncbi.nlm.nih.gov/pubmed/15570087?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。放疗可一天一次(大概 60~70 Gy,每次 2 Gy)或者一天 2 次(45 Gy,每次 1.5 Gy)。[41]Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340:265-271.http://www.nejm.org/doi/full/10.1056/NEJM199901283400403#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/9920950?tool=bestpractice.com死亡率减低:有高质量证据表明,一天两次放疗比一天一次更为有效。[42]Auperin A, Arriagada R, Pignon JP, et al; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999;341:476-484.http://www.nejm.org/doi/full/10.1056/NEJM199908123410703#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/10441603?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。一项对比不同放射剂量方式的随机研究正在进行。[43]National Cancer Institute/Radiation Therapy Oncology Group. Three different radiation therapy regimens in treating patients with limited-stage small cell lung cancer receiving cisplatin and etoposide: NCT00632853. http://www.clinicaltrials.gov (last accessed 30 August 2016).http://www.clinicaltrials.gov/ct2/show/NCT00632853
手术干预在 SCLC 中的作用有限,因为大多数患者处于疾病晚期。对于只有单个肺肿块而没有淋巴结病影像学证据的少数患者,建议进行术前纵膈镜检查来确认 N0 状态。对于这些患者进行手术切除,通常是肺叶切除是合理的。随后应进行术后化疗。[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: small cell lung cancer. 2016. http://www.nccn.org (last accessed 30 August 2016).http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
扩散期疾病
扩散期 SCLC 患者通常接受化疗,一般为 4 到 6 个周期。[44]Pelayo Alvarez M, Westeel V, Cortés-Jofré M, et al. Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev. 2013;(11):CD001990.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001990.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19821287?tool=bestpractice.com常用的方案包括顺铂和依托泊苷、卡铂和依托泊苷、以及顺铂和伊立替康。
放疗可以用来减轻出现症状的部位,包括肺、骨和脑。转移灶较为局限的患者,在最初化疗时达到胸腔外完全缓解以及胸腔内至少部分缓解的情况下,应该考虑胸腔放疗延缓或防止症状复发。[45]Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol. 1999;17:2092-2099.http://www.ncbi.nlm.nih.gov/pubmed/10561263?tool=bestpractice.com[46]Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015;385:36-42.http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61085-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25230595?tool=bestpractice.com
预防性头颅照射 (PCI)
SCLC 患者发展为脑转移的风险较高。随机试验显示,进行预防性头颅照射 (PCI) 能使对初始疗法有反应的患者获得生存获益。局限期疾病的数据比扩散期疾病的数据更有力。多个随机试验的 meta 分析表明与观察组相比,脑转移发生率降低以及进行 PCI 的死亡率更低。[42]Auperin A, Arriagada R, Pignon JP, et al; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999;341:476-484.http://www.nejm.org/doi/full/10.1056/NEJM199908123410703#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/10441603?tool=bestpractice.com此 meta 分析中的小部分患者患有扩散期疾病。最近,一些研究尝试证实 PCI 在扩散期 SCLC 中的潜在效益。一项随机试验将扩散期 SCLC 患者分至 PCI 组和观察组,并对两组进行比较,发现 PCI 组中症状性脑转移的发生率更低以及无病生存期和总生存期增加;但是,这项调查因为在筛查时没有要求患者进行脑部 MRI 检查而受到批评,因此,不清楚患者是否正在接受 PCI 术或放射疗法。[47]Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357:664-672http://www.nejm.org/doi/full/10.1056/NEJMoa071780#t=articleTophttp://www.ncbi.nlm.nih.gov/pubmed/17699816?tool=bestpractice.com一项随机试验对 PCI 组和观察组的扩散期疾病患者进行了比较,该研究因无效果而被较早停止,然而 PCI 组中脑转移的发生率降低,但总生存期结果较差,虽然其统计学意义并不显著。[48]Seto T, Takahashi T, Yamanaka T, et al. Prophylactic cranial irradiation (PCI) has a detrimental effect on the overall survival (OS) of patients (pts) with extensive disease small cell lung cancer (ED-SCLC): Results of a Japanese randomized phase III trial. 2014 ASCO Annual Meeting Abstracts. J Clin Oncol. 2014;32(15 suppl):7503.http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/7503?sid=1106a545-44fc-429e-a3b6-07ddfc414a26在接受 PCI 的患者中,推荐剂量为 25 Gy,每次 2.5 Gy,或者 30 Gy,每次 1.8 Gy 至 2 Gy。一项随机试验显示 25 Gy 和 36 Gy 方案之间,2 年内脑转移发生率没有差异,但高剂量方案的毒性更高。[49]Le Péchoux C, Dunant A, Senan S, et al. Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy: a randomised clinical trial. Lancet Oncol. 2009;10:467-474.http://www.ncbi.nlm.nih.gov/pubmed/19386548?tool=bestpractice.com[50]Le Péchoux C, Laplanche A, Faivre-Finn C, et al; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol. 2011;22:1154-1163.http://annonc.oxfordjournals.org/content/22/5/1154.longhttp://www.ncbi.nlm.nih.gov/pubmed/21139020?tool=bestpractice.comPCI 并不推荐用于低 PS 评分或有脑功能损伤的患者。
复发
国立癌症综合研究网络 (NCCN) 指南对复发患者推荐的方案。[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: small cell lung cancer. 2016. http://www.nccn.org (last accessed 30 August 2016).http://www.nccn.org/professionals/physician_gls/f_guidelines.asp建议对早期复发(6 个月内复发)和远期复发(6 个月以后复发)患者采用个体化治疗方案。