Hazuka M B, Crowley J J, Bunn P A, O'Rourke M, Braun T J, Livingston R B
University of Michigan Medical Center, Ann Arbor.
J Clin Oncol. 1994 Sep;12(9):1814-20. doi: 10.1200/JCO.1994.12.9.1814.
This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin.
Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (i.v.) cisplatin (5 mg/m2) plus concurrent continuous-course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m2 or subsequently 50 mg/m2 administered i.v. on days 1 and 8 of each cycle.
Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively.
Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated out-patient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.
本单臂II期试验旨在评估持续疗程、高剂量胸部放疗（RT）联合每日低剂量顺铂同步治疗，随后进行高剂量顺铂巩固治疗，对局部晚期不可切除非小细胞肺癌（NSCLC）患者的疗效和毒性。每日化疗方案旨在优化顺铂的放射增敏特性。
1989年4月至1991年5月期间，来自21个参与机构的65例患者进入本研究。方案治疗包括每周周一至周五每日静脉注射（i.v.）顺铂（5 mg/m²）加同步持续疗程放疗（6.5周内61 Gy）。经过3至4周的休息期后，接着进行三个28天周期的顺铂治疗，剂量为100 mg/m²，或随后每个周期的第1天和第8天静脉注射50 mg/m²。
64例患者符合条件；大多数患者患有不可切除的IIIa期（36%）或IIIb期（55%）NSCLC。其余9%的患者患有局限于胸部的复发性疾病（5例患者）或II期疾病（1例患者）。该方案的可行性体现在仅有5例患者（8%）因毒性无法完成每日顺铂和放疗。食管炎（16%）、白细胞减少（14%）、恶心（8%）和呕吐（6%）是最常见的严重（3级）毒性反应。仅有1例危及生命的毒性反应（4级恶心），且无治疗相关死亡。客观缓解率为39%，6例患者（9%）实现影像学完全缓解（CR）。所有患者的中位生存时间为14个月，1年和2年精算生存率分别为56%和24%。对于IIIa期患者，中位生存时间和2年生存率分别为17个月和38%，而IIIb期患者分别为10个月和14%。
每日低剂量顺铂加同步高剂量持续疗程放疗是一种耐受性良好的门诊治疗方案。生存结果令人鼓舞，似乎等同于毒性更强的联合治疗方法。这些结果值得进一步测试每日铂类类似物与放疗的联合应用。
