Sause W T, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran W J, Byhardt R W, Turrisi A T
Radiation Therapy Department, LDS Hospital, UT 84143, USA.
J Natl Cancer Inst. 1995 Feb 1;87(3):198-205. doi: 10.1093/jnci/87.3.198.
Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy.
On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy.
Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy).
Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03).
In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.
局部晚期、手术无法切除的非小细胞肺癌是一种预后极差的疾病。对原发肿瘤和区域淋巴结进行外照射通常被认为是标准治疗方法。采用更积极的放疗方案以及在放疗中加入细胞毒性化疗的效果存在争议。然而，最近使用创新放疗技术或放疗前化疗的临床试验结果表明，采用包含这些改良措施方案治疗的患者可能比接受标准放疗的患者有更高的生存率。
基于这些结果，放射肿瘤学组（RTOG）-东部肿瘤协作组（ECOG）决定开展一项III期试验，比较以下方案：1）标准放疗；2）诱导化疗后进行标准放疗；3）每日两次放疗。
手术无法切除的II期、IIIA期或IIIB期非小细胞肺癌患者为潜在受试者。分期采用非手术方式。患者入组试验前需卡氏评分70分及以上，且在入组前3个月体重减轻少于5%，年龄大于18岁，无转移性疾病。在该试验登记的490例患者中，452例符合条件。95%患者的疾病为IIIA期或IIIB期。超过三分之二的患者卡氏评分高于80分。患者被随机分配接受以下治疗之一：6周内每周5天、每次2 Gy、共60 Gy的放疗（标准放疗）；诱导化疗，第1天和第29天给予顺铂（100 mg/m²），从第1天开始与顺铂联合，每周连续5周给予长春花碱5 mg/m²，然后从第50天开始进行标准放疗；或每天两次、每次1.2 Gy、共69.6 Gy的超分割放疗。
毒性反应可接受，有4例与治疗相关的死亡。3例患者随后死于慢性肺部并发症。方案治疗的依从性可接受。1年生存率（%）和中位生存期（月）如下：标准放疗——46%，11.4个月；化疗加放疗——60%，13.8个月；超分割放疗——51%，12.3个月。化疗加放疗组在统计学上优于其他两个治疗组（对数秩检验P = 0.03）。
在手术无法切除的“低危”非小细胞肺癌患者中，诱导化疗后放疗优于超分割放疗或单纯标准放疗，在统计学上有显著的短期生存优势。
