Deutsch M, Crawford J, Leopold K, Wolfe W, Foster W, Herndon J, Blackwell S, Yost R
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Cancer. 1994 Aug 15;74(4):1243-52. doi: 10.1002/1097-0142(19940815)74:4<1243::aid-cncr2820740411>3.0.co;2-d.
The purpose of this study was to assess the ability of administering to patients induction chemotherapy with carboplatin and etoposide (VP-16), followed by full-course radiation therapy and weekly carboplatin with tolerable toxicity as preoperative therapy to down-stage disease thus allowing the resection of clinically staged IIIA non-small cell lung cancer.
Twenty-eight eligible patients with good performance status and previously untreated, marginally resectable stage IIIA non-small cell lung cancer received induction chemotherapy with carboplatin (dosed per the Egorin formulation), and VP-16 (100 mg/m2) followed by 6000 cGy of chest radiotherapy over six weeks administered concurrently with weekly doses of 100 mg/m2 of carboplatin. Patients who had either responsive or stable disease underwent thoracotomy, with attempted surgical resection of the primary lung lesion and the areas of abnormal adenopathy. Procedures involving less than a pneumonectomy were used whenever feasible.
Fifty-two cycles of induction chemotherapy were administered. The average initial dose of carboplatin was 407 mg/m2. Toxicity was tolerable with grade 3-4 neutropenia and/or thrombocytopenia in 48 and 27% of the patients. There were no septic deaths. Full-dose radiotherapy was administered to 82% of patients, with 73% receiving at least five weekly doses of carboplatin. The radiographically assessed response rate to the neoadjuvant treatment was 64% (partial response, 46%; minimal response, 18%). Sixteen patients underwent gross tumor resection with 12 (43%) having negative pathologic margins. Six patients had pneumonectomy. There were three perioperative deaths (19%); two were secondary to respiratory failure after the patients underwent a pneumonectomy. The median survival for all 28 patients was 15 months, and for the 16 patients undergoing thoracotomy was 23 months. Eight patients were alive and in remission, with follow-up ranging from 8 to 31 months.
The authors conclude that (1) carboplatin and VP-16, followed by full-dose radiotherapy with weekly carboplatin administration, is a well tolerated and effective regimen in the treatment of patients with marginally resectable stage IIIA non-small cell lung cancer; and (2) full-course radiotherapy can be administered before surgical resection without additional surgical morbidity or mortality.
本研究的目的是评估对患者给予卡铂和依托泊苷（VP - 16）进行诱导化疗，随后进行全疗程放疗以及每周给予卡铂且毒性可耐受作为术前治疗以降低疾病分期，从而实现对临床分期为IIIA期的非小细胞肺癌进行切除的能力。
28例符合条件、身体状况良好且既往未接受过治疗、边缘可切除的IIIA期非小细胞肺癌患者接受了卡铂（按照埃戈林公式给药）和VP - 16（100 mg/m²）的诱导化疗，随后在六周内给予6000 cGy的胸部放疗，同时每周给予100 mg/m²的卡铂。疾病有反应或稳定的患者接受开胸手术，尝试手术切除原发性肺病变及异常淋巴结区域。只要可行，就采用少于全肺切除术的手术方式。
共进行了52个周期的诱导化疗。卡铂的平均初始剂量为407 mg/m²。48%的患者出现3 - 4级中性粒细胞减少和/或27%的患者出现血小板减少，毒性可耐受。无感染性死亡病例。82%的患者接受了全剂量放疗，73%的患者至少接受了五周的卡铂治疗。新辅助治疗的影像学评估缓解率为64%（部分缓解，46%；最小缓解，18%）。16例患者进行了大体肿瘤切除，其中12例（43%）病理切缘阴性。6例患者接受了全肺切除术。围手术期死亡3例（19%）；2例继发于全肺切除术后的呼吸衰竭。28例患者全部患者的中位生存期为15个月，接受开胸手术的16例患者的中位生存期为23个月。8例患者存活且病情缓解，随访时间为8至31个月。
作者得出结论：（1）卡铂和VP - 16，随后进行全剂量放疗并每周给予卡铂，是治疗边缘可切除的IIIA期非小细胞肺癌患者耐受性良好且有效的方案；（2）全疗程放疗可在手术切除前进行，且不会增加手术并发症或死亡率。
