Wolff A C, Ettinger D S, Neuberg D, Comis R L, Ruckdeschel J C, Bonomi P D, Johnson D H
Johns Hopkins Oncology Center, Baltimore, MD, USA.
J Clin Oncol. 1995 Jul;13(7):1615-22. doi: 10.1200/JCO.1995.13.7.1615.
A phase II study of ifosfamide, carboplatin, and prolonged oral administration of etoposide (ICE) in patients with untreated extensive-disease (ED) small-cell lung cancer (SCLC) was conducted to assess toxicities, response, and median survival.
Between July 1990 and August 1992, 35 patients were treated. ICE doses were ifosfamide 5 g/m2 by 24-hour continuous intravenous (CIV) infusion with mesna on day 1, carboplatin 300 mg/m2 intravenously (IV) on day 1, and etoposide 50 mg/m2 orally on days 1 to 21 every 4 weeks for up to six to eight cycles (schedule I). Because of severe hematologic toxicity in the first 18 patients, the last 17 patients received ifosfamide 3.75 mg/m2 IV on day 1, carboplatin 300 mg/m2 IV on day 1, and etoposide 50 mg orally on days 1 to 14 (schedule II).
Nine of 18 patients (50%) on schedule I had 13 episodes of severe hematologic toxicity (one death), and only two (11%) received full doses on cycle 2. However, with schedule II, only four of 17 patients (24%) developed severe hematologic toxicity, and eight (47%) received full doses on cycle 2. Objective responses were observed in 29 of 35 patients (83%) (schedule 1, 16 of 18 patients [89%]; schedule II, 13 of 17 patients [76%]). There were eight (23%) complete responses (CRs) and 21 (60%) partial responses (PRs). The median survival duration was 8.3 months, and 1- and 2-year survival rates were 37% and 14%, respectively.
ICE with oral etoposide has comparable activity with other regimens in ED SCLC. However, the 2-year survival rate may be higher and ICE with the lower doses of schedule II could be given safely with acceptable toxicity. Further studies of ICE compared with standard two-drug regimens are warranted.
开展一项针对未经治疗的广泛期（ED）小细胞肺癌（SCLC）患者的异环磷酰胺、卡铂及依托泊苷延长口服给药（ICE）的II期研究，以评估毒性、反应及中位生存期。
1990年7月至1992年8月期间，对35例患者进行了治疗。ICE方案的剂量为：第1天异环磷酰胺5 g/m²，通过24小时持续静脉输注（CIV）并同时使用美司钠；第1天卡铂300 mg/m²静脉注射（IV）；每4周第1至21天依托泊苷50 mg/m²口服，最多进行6至8个周期（方案I）。由于前18例患者出现严重血液学毒性，后17例患者接受的方案为：第1天异环磷酰胺3.75 mg/m²静脉注射，第1天卡铂300 mg/m²静脉注射，第1至14天依托泊苷50 mg口服（方案II）。
方案I组的18例患者中有9例（50%）发生了13次严重血液学毒性事件（1例死亡），只有2例（11%）在第2周期接受了全剂量治疗。然而，采用方案II时，17例患者中只有4例（24%）出现严重血液学毒性，8例（47%）在第2周期接受了全剂量治疗。35例患者中有29例（83%）观察到客观反应（方案I，18例患者中的16例[89%]；方案II，17例患者中的13例[76%]）。有8例（23%）完全缓解（CR）和21例（60%）部分缓解（PR）。中位生存期为8.3个月，1年和2年生存率分别为37%和14%。
ICE联合口服依托泊苷在ED SCLC中的活性与其他方案相当。然而，2年生存率可能更高，且方案II较低剂量的ICE可以安全给药，毒性可接受。有必要进一步开展ICE与标准两药方案对比的研究。
