Ettinger D S, Karp J E, Abeloff M D, Burke P J, Braine H G
Cancer Treat Rep. 1978 Mar;62(3):413-24.
Twenty-three patients with small cell carcinoma of the lung (15 with limited disease and eight with extensive disease) were randomized into one of two induction schedules of high-dose cyclophosphamide (CY), 60 mg/kg iv, given either on Days 1 and 2 or on Days 1 and 8. Following the high-dose CY, patients were treated with a sequence of three monthly courses of COMB (CY, 800 mg/m2; vincristine [Oncovin], 1.4 mg/m2; methotrexate, 20 mg/m2; and BCNU, 60 mg/m2) alternating with high-dose CY. The overall response rate to the high-dose CY was 70% with 17% being complete responses (CRs). COMB produced no additional responses. There was no significant difference in response rate with either high-dose CY schedule. There was no unexpected morbidity associated with the intensive regiment despite marked myelosuppression. The high-dose CY administered on Days 1 and 8 appeared less toxic than that given on Days 1 and 2. Laboratory studies demonstrated that small cell carcinoma cells respond to drug-induced humoral stimulation in vitro; and that tumor proliferation in vivo temporally coincides with increased serum stimulatory activity. This study demonstrates that high-dose CY is a safe and effective induction therapy for small cell carcinoma of the lung although the low CR rate obtained is disappointing.
23例肺癌小细胞癌患者（15例为局限性疾病，8例为广泛性疾病）被随机分为两种高剂量环磷酰胺（CY）诱导方案之一，静脉注射60mg/kg，分别在第1天和第2天或第1天和第8天给药。在高剂量CY之后，患者接受一系列为期三个月的COMB方案治疗（CY，800mg/m²；长春新碱[安可平]，1.4mg/m²；甲氨蝶呤，20mg/m²；卡莫司汀，60mg/m²），并与高剂量CY交替使用。高剂量CY的总体缓解率为70%，其中17%为完全缓解（CR）。COMB方案未产生额外缓解。两种高剂量CY方案的缓解率无显著差异。尽管有明显的骨髓抑制，但强化治疗方案未出现意外的发病率。第1天和第8天给予的高剂量CY似乎比第1天和第2天给予的毒性更小。实验室研究表明，小细胞癌细胞在体外对药物诱导的体液刺激有反应；并且体内肿瘤增殖在时间上与血清刺激活性增加相吻合。本研究表明，高剂量CY是一种安全有效的肺癌小细胞癌诱导治疗方法，尽管获得的低CR率令人失望。
