Dillman R O, Herndon J, Seagren S L, Eaton W L, Green M R
Hoag Cancer Center, Newport Beach, CA 92663, USA.
J Natl Cancer Inst. 1996 Sep 4;88(17):1210-5. doi: 10.1093/jnci/88.17.1210.
For many years, high dose radiation therapy was the standard treatment for patients with locally or regionally advanced non-small-cell lung cancer (NSCLC), despite a 5-year survival rate of only 3%-10% following such therapy. From May 1984 through May 1987, the Cancer and Leukemia Group B (CALGB) conducted a randomized trial that showed that induction chemotherapy before radiation therapy improved survival during the first 3 years of follow-up.
This report provides data for 7 years of follow-up of patients enrolled in the CALGB trial.
The patient population consisted of individuals who had clinical or surgical stage III, histologically documented NSCLC; a CALGB performance status of 0-1; less than 5% loss of body weight in the 3 months preceding diagnosis; and radiographically visible disease. Patients were randomly assigned to receive either 1) cisplatin (100 mg/m2 body surface area intravenously on days 1 and 29) and vinblastine (5 mg/m2 body surface area intravenously weekly on days 1, 8, 15, 22, and 29) followed by radiation therapy with 6000 cGy given in 30 fractions beginning on day 50 (CT-RT group) or 2) radiation therapy with 6000 cGy alone beginning on day 1 (RT group) for a maximum duration of 6-7 weeks. Patients were evaluated for tumor regression if they had measurable or evaluable disease and were monitored for toxic effects, disease progression, and date of death.
There were 78 eligible patients randomly assigned to the CT-RT group and 77 randomly assigned to the RT group. Both groups were similar in terms of sex, age, histologic cell type, performance status, substage of disease, and whether staging had been clinical or surgical. All patients had measurable or evaluable disease at the time of random assignment to treatment groups. Both groups received a similar quantity and quality of radiation therapy. As previously reported, the rate of tumor response, as determined radiographically, was 56% for the CT-RT group and 43% for the RT group (P = .092). After more than 7 years of follow-up, the median survival remains greater for the CT-RT group (13.7 months) than for the RT group (9.6 months) (P = .012) as ascertained by the logrank test (two-sided). The percentages of patients surviving after years 1 through 7 were 54, 26, 24, 19, 17, 13, and 13 for the CT-RT group and 40, 13, 10, 7, 6, 6, and 6 for the RT group.
Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival. The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone. However, inasmuch as 80%-85% of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone, the need for further improvements in both the local and systemic treatment of this disease persists.
多年来，高剂量放射治疗一直是局部或区域晚期非小细胞肺癌（NSCLC）患者的标准治疗方法，尽管接受这种治疗后的5年生存率仅为3%-10%。1984年5月至1987年5月，癌症与白血病B组（CALGB）进行了一项随机试验，结果显示放疗前进行诱导化疗可提高随访前3年的生存率。
本报告提供了CALGB试验入组患者7年随访的数据。
患者群体包括临床或手术分期为III期、组织学确诊为NSCLC的个体；CALGB体能状态为0-1；诊断前3个月体重减轻少于5%；以及影像学可见疾病。患者被随机分配接受以下两种治疗之一：1）顺铂（第1天和第29天静脉注射100mg/m²体表面积）和长春花碱（第1、8、15、22和29天每周静脉注射5mg/m²体表面积），随后从第50天开始分30次给予6000cGy放射治疗（CT-RT组）；或2）仅从第1天开始给予6000cGy放射治疗（RT组），最长持续6-7周。对有可测量或可评估疾病的患者评估肿瘤消退情况，并监测毒性作用、疾病进展和死亡日期。
有78例符合条件的患者被随机分配到CT-RT组，77例被随机分配到RT组。两组在性别、年龄、组织学细胞类型、体能状态、疾病亚分期以及分期是临床分期还是手术分期方面相似。所有患者在随机分配到治疗组时均有可测量或可评估疾病。两组接受的放射治疗的量和质量相似。如先前报道，通过影像学确定的肿瘤反应率，CT-RT组为56%，RT组为43%（P = .092）。经过7年多的随访，通过对数秩检验（双侧）确定，CT-RT组的中位生存期（13.7个月）仍高于RT组（9.6个月）（P = .012）。CT-RT组1至7年存活患者的百分比分别为54%、26%、24%、19%、17%、13%和13%，RT组分别为40%、13%、10%、7%、6%、6%和6%。
长期随访证实，III期NSCLC患者在放射治疗前接受5周顺铂和长春花碱化疗，中位生存期增加4.1个月。与单纯放疗相比，序贯化疗-放疗使预计的5年生存者比例提高了2.8倍。然而，由于80%-85%的此类患者仍在5年内死亡，并且无论是接受序贯化疗-放疗还是单纯放疗的患者，治疗失败都发生在照射野内和远处部位，因此对这种疾病的局部和全身治疗进一步改进的需求仍然存在。
