Hofheinz Ralf, Hartung Gernot, Samel Stefan, Emig Michael, Pilz Lothar, Willeke Frank, Hochhaus Andreas, Hehlmann Rüdiger, Queisser Wolfgang
Onkologisches Zentrum, III Medizinische Klinik.
Anticancer Drugs. 2002 Nov;13(10):999-1004. doi: 10.1097/00001813-200211000-00003.
Irinotecan (CPT-11) has been shown to prolong survival and improve quality of life in comparison to best supportive care in colorectal cancer patients with pretreatment of bolus 5-fluorouracil (5-FU). After first-line 24-h high-dose (HD) 5-FU/folinic acid (FA) an objective response rate of 11% with 3-weekly CPT-11 350 mg/m was reported. In the present study we investigated weekly CPT-11 in combination with 24-h HD-5-FU/FA as second-line treatment after prior exposure to 24-h HD-5-FU. Synergy between 5-FU and CPT-11 is the rationale to combine both substances for second-line therapy in order to overcome resistance to 5-FU. Thirty-five patients were recruited in a single institution to receive 6 x weekly CPT-11 80 mg/m(2), FA 200 mg/m(2) and 24-h HD-5-FU 2000 mg/m(2). Treatment was repeated on day 57.
M/F=20/15, median WHO performance status 1, range (0-2). Thirty-four patients were evaluable for response: partial response 17% and no change 40%. Median time to progression and overall survival were 3.3 and 8.4 months, respectively. All patients were evaluable for toxicity analysis (National Cancer Institute Common Toxicity Criteria grade 3): leukocytopenia 3%, diarrhea 12% and vomiting/nausea 6%. Of the assigned doses, a median 100% of 5-FU and 92% of CPT-11 were administered during the first cycle of chemotherapy. We conclude that weekly CPT-11 and HD-5-FU/FA is an active and safe combination chemotherapy resulting in response rates in the upper range of other CPT-11-based second-line regimen. The toxicity profile in our series compared to 3-weekly CPT-11 seems favorable.
与接受大剂量推注 5-氟尿嘧啶（5-FU）预处理的结直肠癌患者的最佳支持治疗相比，伊立替康（CPT-11）已显示可延长生存期并改善生活质量。在一线 24 小时高剂量（HD）5-FU/亚叶酸（FA）治疗后，报告了每 3 周给予 350mg/m²CPT-11 的客观缓解率为 11%。在本研究中，我们调查了每周给予 CPT-11 联合 24 小时 HD-5-FU/FA 作为先前接受 24 小时 HD-5-FU 治疗后的二线治疗。5-FU 和 CPT-11 之间的协同作用是将这两种药物联合用于二线治疗以克服对 5-FU 耐药的理论依据。在单一机构招募了 35 名患者，接受每周 6 次 80mg/m²CPT-11、200mg/m²FA 和 24 小时 2000mg/m²HD-5-FU 治疗。在第 57 天重复治疗。
男/女 = 20/15，世界卫生组织体能状态中位数为 1，范围（0 - 2）。34 名患者可评估缓解情况：部分缓解 17%，病情稳定 40%。疾病进展时间中位数和总生存期分别为 3.3 个月和 8.4 个月。所有患者均可评估毒性（美国国立癌症研究所通用毒性标准 3 级）：白细胞减少 3%，腹泻 12%，呕吐/恶心 6%。在化疗的第一个周期中，5-FU 和 CPT-11 的给药剂量中位数分别为 100%和 92%。我们得出结论，每周给予 CPT-11 和 HD-5-FU/FA 是一种有效且安全的联合化疗方案，缓解率处于其他基于 CPT-11 的二线治疗方案的较高范围。与每 3 周给予 CPT-11 相比，我们系列中的毒性特征似乎更好。
