Conti J A, Kemeny N E, Saltz L B, Huang Y, Tong W P, Chou T C, Sun M, Pulliam S, Gonzalez C
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY, USA.
J Clin Oncol. 1996 Mar;14(3):709-15. doi: 10.1200/JCO.1996.14.3.709.
To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer.
Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90-minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo-I) activity were obtained from 11 patients. The pharmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients.
Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenyldramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea.
Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients.
确定新型抗癌药物伊立替康（CPT - 11）治疗转移性结直肠癌的缓解率、生存率及毒性。
41例初治的可测量转移性结直肠癌患者接受伊立替康125mg/m²静脉输注90分钟，每周1次，共4周，每6周重复。11例患者于治疗前取肿瘤活检组织以评估拓扑异构酶 - I（Topo - I）活性。18例患者测定了伊立替康及其活性代谢产物SN - 38的药代动力学。
41例患者中有13例（32%）获得部分缓解（PR；95%置信区间为18%至46%）。41例患者的中位缓解持续时间为8.1个月（范围4.0至16.0个月），中位生存时间为12.1个月（范围2.1至21.7个月）。3或4级毒性反应为腹泻（29%的患者）和中性粒细胞减少（22%的患者）。在最初入组的18例患者中，3或4级腹泻更为常见，发生率为56%；严格遵循洛哌丁胺和苯海拉明的止泻方案后，严重腹泻的发生率显著降低至9%。未发现伊立替康/SN - 38的药代动力学与缓解、生存或腹泻发生率的临床参数之间存在相关性。
伊立替康对转移性结直肠癌患者有治疗活性。严格遵循苯海拉明/洛哌丁胺的止泻方案可显著降低腹泻发生率；此后大多数患者对该药物耐受性良好。
