Verschraegen C F, Levy T, Kudelka A P, Llerena E, Ende K, Freedman R S, Edwards C L, Hord M, Steger M, Kaplan A L, Kieback D, Fishman A, Kavanagh J J
University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Clin Oncol. 1997 Feb;15(2):625-31. doi: 10.1200/JCO.1997.15.2.625.
A phase II study was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11), a water-soluble derivative of camptothecin, in patients with prior chemotherapy-treated squamous cell cancer of the cervix.
Forty-two patients were included in the study. The median age was 44 years (range, 24 to 59 years). The median Zubrod performance status was 1. All patients were refractory to first-line chemotherapy and 88% had received prior radiotherapy. The initial dose of CPT-11 was 125 mg/m2 given as a weekly 90-minute intravenous infusion for 4 weeks, every 6 weeks. Subsequent doses were unchanged, reduced, or omitted according to toxicity grade.
Forty-two patients were assessable for response. The overall response rate was 21%. The median time to response was 6 weeks and the median duration of response was 12 weeks. The overall median duration of survival was 6.4 months. A statistically significant survival advantage (median of 12.6 v 5.1 months) was found in patients whose disease responded to the treatment (P < .015). The major dose-limiting toxic effects (grade > or = 3) were nausea and vomiting (45%), diarrhea (24%), and granulocytopenia (36%). Grade > or = 3 anemia was encountered in 62% of patients and the incidence of thrombocytopenia was negligible. Less severe side effects were alopecia (48%), drug fever (43%), anorexia (33%), fatigue (33%), skin rash (21%), stomatitis (14%), and allergic reaction (9%). The gastrointestinal intolerance was dose-related. The incidence of bone marrow depression did not decrease with dose reduction, possibly because of a cumulative effect or hematologic intolerance by a subset of patients.
CPT-11 has significant activity in refractory cervical carcinoma. Gastrointestinal intolerance and hematologic toxicity must be monitored carefully. Further studies of alternative schedules may improve the tolerance and response rate.
开展一项II期研究，以评估喜树碱的水溶性衍生物伊立替康（CPT - 11）对先前接受过化疗的宫颈鳞状细胞癌患者的抗肿瘤活性和毒性。
42例患者纳入本研究。中位年龄为44岁（范围24至59岁）。Zubrod体能状态中位数为1。所有患者对一线化疗均耐药，88%的患者曾接受过放疗。CPT - 11的初始剂量为125mg/m²，每6周进行一次，每周静脉输注90分钟，共4周。后续剂量根据毒性分级保持不变、减少或省略。
42例患者可评估疗效。总缓解率为21%。中位缓解时间为6周，中位缓解持续时间为12周。总生存时间中位数为6.4个月。疾病对治疗有反应的患者具有统计学显著的生存优势（中位数为12.6对5.1个月）（P <.015）。主要剂量限制性毒性作用（≥3级）为恶心和呕吐（45%）、腹泻（24%）和粒细胞减少（36%）。62%的患者出现≥3级贫血，血小板减少发生率可忽略不计。较轻的副作用包括脱发（48%）、药物热（43%）、厌食（33%）、疲劳（33%）、皮疹（21%）、口腔炎（14%）和过敏反应（9%）。胃肠道不耐受与剂量相关。骨髓抑制的发生率不会因剂量减少而降低，可能是由于累积效应或部分患者的血液学不耐受。
CPT - 11对难治性宫颈癌具有显著活性。必须仔细监测胃肠道不耐受和血液学毒性。对替代给药方案的进一步研究可能会提高耐受性和缓解率。
