Rougier P, Bugat R, Douillard J Y, Culine S, Suc E, Brunet P, Becouarn Y, Ychou M, Marty M, Extra J M, Bonneterre J, Adenis A, Seitz J F, Ganem G, Namer M, Conroy T, Negrier S, Merrouche Y, Burki F, Mousseau M, Herait P, Mahjoubi M
Institut Gustave Roussy, Villejuif, France.
J Clin Oncol. 1997 Jan;15(1):251-60. doi: 10.1200/JCO.1997.15.1.251.
To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients.
Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function.
Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern.
CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.
评估伊立替康（CPT - 11）在初治及经治的晚期结直肠癌患者中的治疗效果。
213例年龄在18至75岁之间、患有转移性结直肠癌、世界卫生组织（WHO）体能状态≤2且预期寿命≥3个月的患者，每3周接受350mg/m²的CPT - 11治疗。所有178例符合疗效分析条件的患者此前接受基于氟尿嘧啶（5 - FU）的化疗方案（辅助或姑息性）不超过一种，且具备良好的血液学、肾脏及肝脏功能。
原发肿瘤部位为结肠（71%）和直肠（28%）。66%的患者有≥两个转移部位。98%的患者曾接受过手术，77.5%的患者曾接受过化疗。178例符合条件的患者中，32例获得客观缓解（4例完全缓解[CR]和28例部分缓解[PR]；缓解率为18%；95%置信区间为12.6%至24.4%），65例病情稳定，59例病情进展。经治组缓解率为17.7%，初治组为18.8%。在前一亚组中，此前接受5 - FU化疗病情进展的患者缓解率为16.1%，未接受此类治疗病情进展的患者缓解率为19.1%。初治患者与经治患者的客观缓解中位持续时间（9.1个月）及达到缓解的中位时间（9.3周）无差异。最常见的不良事件为中性粒细胞减少，80%的患者出现该症状，延迟性腹泻（87%）、脱发（88%）、疲劳（81%）以及恶心/呕吐（77%）。所有这些不良事件均可控制。严重（WHO 3级或4级）中性粒细胞减少仅在18%的疗程中出现，白细胞减少在11%的疗程中出现，延迟性腹泻在11%的疗程中出现，恶心和呕吐在3%的疗程中出现。4%的疗程中同时出现3级或4级中性粒细胞减少和延迟性腹泻是最值得关注的安全问题。
CPT - 11在初治及曾接受5 - FU治疗后病情进展的经治晚期转移性结直肠癌患者的治疗中具有确切疗效，这表明CPT - 11与5 - FU之间不存在交叉耐药性。腹泻和中性粒细胞减少作为CPT - 11的主要毒性反应，增加了发生发热性中性粒细胞减少性败血症的风险。
