Rothenberg M L, Eckardt J R, Kuhn J G, Burris H A, Nelson J, Hilsenbeck S G, Rodriguez G I, Thurman A M, Smith L S, Eckhardt S G, Weiss G R, Elfring G L, Rinaldi D A, Schaaf L J, Von Hoff D D
University of Texas Health Science Center at San Antonio, TX, USA.
J Clin Oncol. 1996 Apr;14(4):1128-35. doi: 10.1200/JCO.1996.14.4.1128.
To evaluate irinotecan (CPT-11; Yakult Honsha, Tokyo, Japan) in patients with metastatic colorectal carcinoma that had recurred or progressed following fluorouracil (5-FU)-based therapy.
Patients were treated with irinotecan 125 to 150 mg/m2 intravenously (IV) every week for 4 weeks, followed by a 2-week rest. Forty-eight patients were entered onto the study and all were assessable for toxicity. Forty-three patients completed one full course of therapy and were assessable for response.
One complete and nine partial responses were observed (response rate, 23%; 95% confidence interval [CI], 10% to 36%). The median response duration was 6 months (range, 2 to 13). The median survival time was 10.4 months and the 1-year survival rate was 46% (95% CI, 39% to 53%). Grade 4 diarrhea occurred in four of the first nine patients (44%) treated on this study at the 150-mg/m2 dose level. The study was amended to reduce the starting dose of irinotecan to 125 mg/m2. At this dose, nine of 39 patients (23%) developed grade 4 diarrhea. Aggressive administration of loperamide also reduced the incidence of grade 4 diarrhea. Grade 4 neutropenia occurred in eight of 48 patients (17%), but was associated with bacteremia and sepsis in only case.
Irinotecan has significant single-agent activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. The incidence of severe diarrhea is reduced by using a starting dose of irinotecan 125 mg/m2 and by initiating loperamide at the earliest signs of diarrhea. These results warrant further clinical evaluation to define the role of irinotecan in the treatment of individuals with colorectal cancer.
评估伊立替康（CPT - 11；日本东京养乐多本社）对接受氟尿嘧啶（5 - FU）为基础治疗后复发或进展的转移性结直肠癌患者的疗效。
患者接受伊立替康125至150mg/m²静脉注射（IV），每周1次，共4周，随后休息2周。48例患者进入本研究，所有患者均可评估毒性。43例患者完成了一个完整疗程的治疗，可评估疗效。
观察到1例完全缓解和9例部分缓解（缓解率为23%；95%置信区间[CI]，10%至36%）。中位缓解持续时间为6个月（范围，2至13个月）。中位生存时间为10.4个月，1年生存率为46%（95%CI，39%至53%）。在本研究中，最初接受150mg/m²剂量水平治疗的9例患者中有4例（44%）发生4级腹泻。研究进行了修正，将伊立替康的起始剂量降至125mg/m²。在此剂量下，39例患者中有9例（23%）发生4级腹泻。积极使用洛哌丁胺也降低了4级腹泻的发生率。48例患者中有8例（17%）发生4级中性粒细胞减少，但仅1例与菌血症和脓毒症相关。
伊立替康对在以5 - FU为基础的化疗期间或之后不久进展的结直肠癌具有显著的单药活性。使用125mg/m²的伊立替康起始剂量并在腹泻最早迹象出现时开始使用洛哌丁胺可降低严重腹泻的发生率。这些结果值得进一步的临床评估，以确定伊立替康在结直肠癌治疗中的作用。
