Ychou M, Raoul J L, Desseigne F, Borel C, Caroli-Bosc F X, Jacob J H, Seitz J F, Kramar A, Hua A, Lefebvre P, Couteau C, Merrouche Y
CRLC Val d'Aurelle, 31 Rue de la croix verte, 34298 Montpellier cedex 05, France.
Cancer Chemother Pharmacol. 2002 Nov;50(5):383-91. doi: 10.1007/s00280-002-0506-7. Epub 2002 Sep 26.
The efficacy and safety of single-agent, high-dose irinotecan (CPT-11, Campto) 500 mg/m(2) every 3 weeks were investigated as first-line treatment for advanced colorectal cancer (CRC).
Patients were enrolled into the study to receive a first cycle of therapy with irinotecan at a dose of 350 mg/m(2) every 3 weeks, which could be escalated to 500 mg/m(2) for the second and subsequent cycles depending on toxicity. Efficacy, safety and pharmacokinetics were determined in the intent to treat (ITT) population and the high-dose population (i.e. patients who had received at least three cycles of irinotecan, the second and third at 500 mg/m(2)).
Of 49 patients enrolled into the study (ITT population), 31 (63%) received at least three cycles of treatment with cycles 2 and 3 at an irinotecan dose of 500 mg/m(2) (the high-dose population). The response rates (RR) for the ITT and high-dose populations were 24.5% and 35.5%, respectively. The main grade 3/4 toxicities per cycle in the ITT and high-dose populations were neutropenia 22% and 17%, febrile neutropenia 5% and 3%, and diarrhoea 12% and 7%, respectively. The pharmacokinetics of irinotecan and its metabolite SN-38 were investigated in 31 patients in cycle 1 and 22 patients in cycle 2. Irinotecan clearance and SN-38 exposure were not sufficiently correlated with toxicity in cycle 1 to identify patients for dose increase in subsequent cycles. The exposure to irinotecan and SN-38 increased in proportion to dose from 350 to 500 mg/m(2).
These results suggest that high-dose irinotecan can be safely administered as first-line monotherapy to approximately two-thirds of patients who present with advanced CRC following a selective first cycle.
研究单药高剂量伊立替康（CPT - 11，开普拓）每3周500mg/m²作为晚期结直肠癌（CRC）一线治疗的疗效和安全性。
患者入组接受伊立替康治疗的首个周期，剂量为每3周350mg/m²，根据毒性情况，第二个及后续周期剂量可增至500mg/m²。在意向性治疗（ITT）人群和高剂量人群（即接受至少三个周期伊立替康治疗的患者，第二个和第三个周期剂量为500mg/m²）中确定疗效、安全性和药代动力学。
入组研究的49例患者（ITT人群）中，31例（63%）接受了至少三个周期的治疗，第2和第3周期伊立替康剂量为500mg/m²（高剂量人群）。ITT人群和高剂量人群的缓解率（RR）分别为24.5%和35.5%。ITT人群和高剂量人群每个周期主要的3/4级毒性分别为中性粒细胞减少22%和17%、发热性中性粒细胞减少5%和3%、腹泻12%和7%。在第1周期的31例患者和第2周期的22例患者中研究了伊立替康及其代谢产物SN - 38的药代动力学。伊立替康清除率和SN - 38暴露量在第1周期与毒性的相关性不足，无法识别后续周期可增加剂量的患者。从350mg/m²至500mg/m²，伊立替康和SN - 38的暴露量与剂量成比例增加。
这些结果表明，高剂量伊立替康作为一线单药治疗，在经过选择性的首个周期后，可安全地用于约三分之二的晚期CRC患者。
