Giaccone G, Dalesio O, McVie G J, Kirkpatrick A, Postmus P E, Burghouts J T, Bakker W, Koolen M G, Vendrik C P, Roozendaal K J
Ospedale S. Giovanni A.S., Torino, Italy.
J Clin Oncol. 1993 Jul;11(7):1230-40. doi: 10.1200/JCO.1993.11.7.1230.
The present study investigates the role of short chemotherapy (five cycles) versus prolonged (12 cycles) chemotherapy in small-cell lung cancer (SCLC).
Six hundred eighty-seven patients with SCLC were registered in a multicenter study to receive five cycles of chemotherapy consisting of cyclophosphamide 1 g/m2 on day 1, doxorubicin 45 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1, 3 and 5 (CDE), every 3 weeks. Four hundred thirty-four nonprogressing patients after five cycles of chemotherapy were randomized either to receive seven further cycles of the same chemotherapy or to follow-up.
The response rate of 585 assessable patients was 79%, with 36% attaining a complete response. Toxicity was mainly hematologic, with 16 toxic deaths (2.4% of all eligible patients), 13 of which were due to sepsis. Median survival time from registration of all patients was 326 days (396 and 267 days for limited and extensive disease, respectively) with 3.2% of patients alive at 5 years. No difference in survival between the two arms was observed, with the same number of 5-year survivors in both arms. The patients randomized to the maintenance arm had a progression-free survival (PFS) duration approximately 2 months longer than the patients randomized to follow-up (median of 177 days v 114 days from randomization; P = .0004). Among patients with a partial response who were randomized to receive maintenance chemotherapy, 12 achieved a complete response after 12 cycles. More patients in the follow-up arm than in the maintenance arm received subsequent treatment on progression and responded more frequently to that treatment. Twelve patients developed second malignancies (seven non-small-cell lung cancers).
Prolonged chemotherapy does not offer a better chance of cure than short chemotherapy (five cycles) and does not prolong survival in patients with SCLC. Short, combination chemotherapy appears to be a reasonable choice for standard treatment of SCLC and for attempts to improve the cure rate of this disease.
本研究探讨短程化疗（5个周期）与长程化疗（12个周期）在小细胞肺癌（SCLC）中的作用。
687例SCLC患者登记参加一项多中心研究，接受每3周1次的化疗，共5个周期，化疗方案为第1天环磷酰胺1 g/m²、第1天阿霉素45 mg/m²、第1、3和5天依托泊苷100 mg/m²（CDE）。434例化疗5个周期后未进展的患者被随机分为两组，一组接受另外7个周期的相同化疗，另一组进行随访。
585例可评估患者的缓解率为79%，其中36%达到完全缓解。毒性主要为血液学毒性，有16例毒性死亡（占所有符合条件患者的2.4%），其中13例死于败血症。所有患者自登记后的中位生存时间为326天（局限性疾病和广泛性疾病分别为396天和267天），5年生存率为3.2%。两组之间未观察到生存差异，两组的5年生存者数量相同。随机分配到维持治疗组的患者无进展生存期（PFS）比随机分配到随访组的患者长约2个月（随机分组后中位时间分别为177天和114天；P = .0004）。在随机接受维持化疗的部分缓解患者中，12例在12个周期后达到完全缓解。随访组比维持治疗组有更多患者在疾病进展后接受后续治疗，且对该治疗的反应更频繁。12例患者发生了第二原发性恶性肿瘤（7例为非小细胞肺癌）。
与短程化疗（5个周期）相比，长程化疗并不能提供更好的治愈机会，也不能延长SCLC患者的生存期。短程联合化疗似乎是SCLC标准治疗以及提高该疾病治愈率尝试的合理选择。
