Thatcher N, Smith D B, Lind M J, Anderson H, Barclay J, Chopra M P, Fitzgerald M D
CRC Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, England.
Cancer. 1988 Jan 1;61(1):14-8. doi: 10.1002/1097-0142(19880101)61:1<14::aid-cncr2820610104>3.0.co;2-q.
Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty-eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future.
对45例晚期非小细胞肺癌（NSCLC）且肿瘤进展无法手术的患者进行了治疗。23例患者处于“局限”期。6例患者曾接受过胸部放疗。排除有中枢神经系统（CNS）转移、卡诺夫斯基评分低于30或高于70的患者以及70岁以上的患者。环磷酰胺（2.5 g/m²）在3小时内静脉输注，美司钠剂量相同。在输注中点，给予3.5 g/m²异环磷酰胺静脉推注。在接下来的8小时内给予额外的美司钠。每三周间隔最多给予四个疗程。共进行了138个疗程，53%的患者完成了全部四个疗程的治疗。缓解率为38%，其中3例（7%）完全缓解。另外7例（15%）病情稳定的患者在治疗结束时卡诺夫斯基评分有两级或更多级的症状改善。45例患者的中位生存期为7个月，范围为不到1个月至25个月。16个疗程出现3级血小板减少和/或白细胞减少（6次为4级，7次为3级），均在化疗前即刻的血常规检查中出现。14%的疗程需要静脉使用抗生素；3例患者死于可能与治疗相关的原因。发生了2次严重的异环磷酰胺脑病，但均完全康复，还发生了4次明显的血尿。化疗结束后1个月，33%的患者卡诺夫斯基评分高于70，而治疗前这一比例为0%。与许多NSCLC化疗方案不同，异环磷酰胺和环磷酰胺联合双烷基化剂治疗在特定患者群体中改善了身体状况且无重大毒性。然而，总体生存期仍然较短，未来需要考虑进一步的烷基化剂联合方案。
