Macchiarini P, Chella A, Riva A, Mengozzi G, Silvano G, Solfanelli S, Angeletti C A
Service of Thoracic Surgery, University of Pisa, Italy.
Am J Clin Oncol. 1990 Dec;13(6):495-500. doi: 10.1097/00000421-199012000-00009.
17 previously untreated patients with small cell lung cancer entered a phase II study testing the feasibility of incorporating high dose epirubicin (110 mg/m2, day 1) in combination regimens, including cyclophosphamide (1 g/m2, day 1), and etoposide (120 mg/m2, day 1) (courses 1, 3, 5) or cisplatin (60 mg/m2, day 1) and etoposide (120 mg/m2, days 1-4) (courses 2, 4, 6), every 3 weeks. Complete responders with limited or extensive disease received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. All patients were evaluable for toxicity and response. Myelosuppression and stomatitis were the dose-limiting side-effects. Maximum myelosuppression occurred as granulocytopenia and anemia, but a recovery by day 21 was observed in the majority of courses. Neutropenic fever occurred in 47 of 99 courses. Severe stomatitis was experienced in 25 courses and lasted generally 7-12 days. Acute cardiac toxicity was uncommon and represented by mild to moderate rhythm abnormalities. No change was noted in the mean QRS voltage on electrocardiogram (ECG) and no patient had a decline of greater than or equal to 20% in the cardiac ejection fraction and/or episode of overt heart failure at any stage of treatment. The overall objective response rate was 88%, with six (35%) complete and nine (53%) partial responses. With a median follow-up of 16 months, overall median survival was 13 months (range, 2-18+). This study demonstrates that epirubicin, at the present dose and schedule, is feasible in combination regimens and that cardiotoxicity is not dose-limiting and induced or enhanced by thoracic irradiation and/or cyclophosphamide.
17例既往未接受过治疗的小细胞肺癌患者进入一项II期研究，该研究旨在测试将高剂量表柔比星（110mg/m²，第1天）纳入联合方案的可行性，联合方案包括环磷酰胺（1g/m²，第1天）和依托泊苷（120mg/m²，第1天）（第1、3、5疗程）或顺铂（60mg/m²，第1天）和依托泊苷（120mg/m²，第1 - 4天）（第2、4、6疗程），每3周进行一次。局限期或广泛期疾病的完全缓解者接受胸部（40Gy）和预防性颅脑（30Gy）照射。所有患者均可评估毒性和反应。骨髓抑制和口腔炎是剂量限制性副作用。最大骨髓抑制表现为粒细胞减少和贫血，但大多数疗程在第21天观察到恢复。99个疗程中有47个出现中性粒细胞减少性发热。25个疗程出现严重口腔炎，通常持续7 - 12天。急性心脏毒性不常见，表现为轻度至中度心律失常。心电图（ECG）上平均QRS电压无变化，且在治疗的任何阶段，没有患者的心脏射血分数下降大于或等于20%和/或出现明显心力衰竭发作。总体客观缓解率为88%，其中6例（35%）完全缓解，9例（53%）部分缓解。中位随访16个月，总体中位生存期为13个月（范围，2 - 18 +）。本研究表明，以目前的剂量和方案，表柔比星在联合方案中是可行的，且心脏毒性不是剂量限制性的，也不会因胸部照射和/或环磷酰胺而诱发或增强。
