Michael Michael, Brittain MaryAnne, Nagai Jane, Feld Ronald, Hedley David, Oza Amit, Siu Lillian, Moore Malcolm J
Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Ontario, Canada.
J Clin Oncol. 2004 Nov 1;22(21):4410-7. doi: 10.1200/JCO.2004.11.125.
The dose-limiting toxicity of irinotecan (CPT-11; Camptosar) is delayed-onset diarrhea, with an incidence at the grade 3 to 4 level of 20% to 35%. SN38, its active moiety, is responsible by a direct effect on mucosal topoisomerase-I. The aim of this study was to assess whether activated charcoal (AC), possibly by adsorbing free lumenal SN38, can reduce irinotecan-induced diarrhea (CID) and optimize its dose-intensity.
Patients with advanced colorectal cancer receiving irinotecan 125 mg/m(2) intravenously once a week for 4 weeks every 6 weeks were studied. In cycle 1, patients received irinotecan plus AC (5 mL aqueous Charcodote [1,000 mg AC] plus 25 mL water) given the evening before the irinotecan dose and then tid for 48 hours after the dose. In cycle 2, no AC was given. National Cancer Institute Common Toxicity Criteria diarrhea grade, irinotecan dose-intensity, and loperamide consumption were recorded prospectively in both cycles.
Twenty-eight patients had completed cycle 1 with AC; 24 subsequently completed cycle 2 without AC. Grade 3 to 4 diarrhea was 7.1% v 25%, and grade 0 diarrhea was 46.4% v 20.8% in cycles 1 and 2, respectively. Median percent planned dose delivered was 98% v 70% in cycles 1 and 2, respectively. In cycles 1 and 2, respectively, 25% v 54% patients took more than 10 loperamide tablets. AC was well tolerated with excellent compliance.
The administration of AC with irinotecan reduced the incidence of grade 3 to 4 diarrhea and antidiarrheal medication consumption and increased irinotecan dose-intensity. Prophylactic AC may have a role in reducing dose-limiting CID and optimizing irinotecan therapy.
伊立替康（CPT - 11；开普拓）的剂量限制性毒性是延迟性腹泻，3至4级腹泻的发生率为20%至35%。其活性部分SN38通过直接作用于黏膜拓扑异构酶 - I起作用。本研究的目的是评估活性炭（AC）是否可能通过吸附肠腔内游离的SN38来减少伊立替康诱导的腹泻（CID）并优化其剂量强度。
研究对象为晚期结直肠癌患者，每6周静脉注射伊立替康125 mg/m²，每周1次，共4周。在第1周期，患者在伊立替康给药前一晚接受伊立替康加AC（5 mL水性活性炭[1000 mg AC]加25 mL水），然后在给药后每8小时1次，共48小时。在第2周期，不给予AC。前瞻性记录两个周期中美国国立癌症研究所通用毒性标准腹泻分级、伊立替康剂量强度和洛哌丁胺消耗量。
28例患者完成了第1周期含AC的治疗；随后24例完成了第2周期不含AC的治疗。第1和第2周期中，3至4级腹泻分别为7.1%和25%，0级腹泻分别为46.4%和20.8%。第1和第2周期中，计划给药剂量的中位数百分比分别为98%和70%。第1和第2周期中，分别有25%和54%的患者服用了超过10片洛哌丁胺。AC耐受性良好，依从性极佳。
伊立替康联合AC给药降低了3至4级腹泻的发生率和止泻药物的消耗量，并提高了伊立替康的剂量强度。预防性使用AC可能在减少剂量限制性CID和优化伊立替康治疗方面发挥作用。
