Rusch V W, Albain K S, Crowley J J, Rice T W, Lonchyna V, McKenna R, Livingston R B, Griffin B R, Benfield J R
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021.
J Thorac Cardiovasc Surg. 1993 Jan;105(1):97-104; discussion 104-6.
Recent studies suggest that preoperative induction chemotherapy +/- radiotherapy can improve the historically poor resectability and survival of patients with stage IIIA non-small-cell lung cancer, but sometimes with significant associated morbidity and mortality. Such treatment has not been studied in stage IIIB non-small-cell lung cancer, usually considered unresectable. This multiinstitutional phase II trial tested the feasibility of concurrent preoperative chemoradiotherapy for stages IIIA and IIIB non-small-cell lung cancer.
Eligible patients had pathologically documented T1-4 N2-3 disease (without pleural effusions). Induction therapy was cisplatin, 50 mg/m2, days 1, 8, 29, and 36 plus VP-16, 50 mg/m2, days 1 to 5, and 29 to 33 plus concurrent radiotherapy (4500 cGy, 180 cGy fractions). Resection was attempted 3 to 5 weeks after induction if the response was stable, partial, or complete. Complete nodal mapping at thoracotomy was required.
One hundred forty-six patients were entered. This interim analysis is based on the first 75 eligible patients for whom complete surgical data are available. There were 49 men and 26 women, median age 58 years (range 32 to 75 years). Sixty-eight of (91%) patients were eligible for operation, and 63 of 75 patients (84%) underwent thoracotomy. Fifty five of 75 patients (73%), including 12 of 16 with a stable response, had a complete resection. Four of 63 patients died postoperatively (6%). Approximately one third required a "complex" resection, for example, lobectomy plus chest wall or spine resection, but mean operating time was 3.2 hours and mean blood loss was less than 1000 ml for both stages IIIA and IIIB. Complete pathology data are currently available from 53 patients: 11 (21%) had no residual tumor; 20 (30%) had rare microscopic foci of residual cancer. The 2-year survival is 40% for both stages IIIA and IIIB.
This combined modality therapy has been well tolerated and has been associated with high response and resectability rates in both stage IIIA and stage IIIB non-small-cell lung cancer. Current survival is significantly better than survivorship among historical control patients and provides a firm basis for subsequent phase III clinical trials.
近期研究表明,术前诱导化疗±放疗可改善ⅢA期非小细胞肺癌患者历来较差的可切除性及生存率,但有时会伴有显著的相关发病率和死亡率。此类治疗尚未在通常被认为不可切除的ⅢB期非小细胞肺癌中进行研究。这项多机构Ⅱ期试验测试了ⅢA期和ⅢB期非小细胞肺癌术前同步放化疗的可行性。
符合条件的患者经病理证实为T1-4 N2-3期疾病(无胸腔积液)。诱导治疗方案为顺铂50mg/m²,于第1、8、29和36天给药,依托泊苷50mg/m²,于第1至5天及29至33天给药,同时进行放疗(4500cGy,每次180cGy)。若诱导治疗后反应稳定、部分缓解或完全缓解,则在3至5周后尝试进行手术切除。开胸手术时需进行完整的淋巴结清扫。
共纳入146例患者。本中期分析基于前75例有完整手术数据的符合条件患者。其中男性49例,女性26例,中位年龄58岁(范围32至75岁)。68例(91%)患者符合手术条件,75例患者中有63例(84%)接受了开胸手术。75例患者中有55例(73%)实现了完全切除,其中包括16例反应稳定患者中的12例。63例患者中有4例术后死亡(6%)。约三分之一的患者需要进行“复杂”切除,例如肺叶切除加胸壁或脊柱切除,但ⅢA期和ⅢB期患者的平均手术时间均为3.2小时,平均失血量均少于1000ml。目前已有53例患者的完整病理数据:11例(21%)无残留肿瘤;20例(30%)有罕见的微小残留癌灶。ⅢA期和ⅢB期患者的2年生存率均为40%。
这种联合治疗耐受性良好,在ⅢA期和ⅢB期非小细胞肺癌中均具有较高的缓解率和可切除率。目前的生存率显著优于历史对照患者,为后续的Ⅲ期临床试验提供了坚实基础。