Phase I study of CPT-11 and bolus 5-FU/l-leucovorin in patients with metastatic colorectal cancer

Hiromitsu Fujishima, Ikuo Kikuchi, Osamu Miyanaga, Akira Ueda, Eishi Baba, Kenji Mitsugi, Mine Harada, Shuji Nakano

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Background. Irinotecan (CPT-11) and bolus 5-fluorouracil (5-FU)/leucovorin (LV) administered weekly for 4 weeks every 42 days (Saltz regimen) is active but substantially toxic in patients with metastatic colorectal cancer (CRC). The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC. Methods. We investigated the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended phase II dose (RD) for CPT-11 given i.v. (90-min infusion) and bolus 5-FU plus biologically active l-LV administered weekly for 3 weeks every 28 days (modified Saltz regimen) in Japanese patients with metastatic CRC. Eighteen patients with measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and adequate organ functions were enrolled. Results. At dose level 2 (CPT-11, 100 mg/m2; 5-FU, 400 mg/m 2; and l-LV, 25 mg/body), 1 of 6 patients had DLT (febrile neutropenia). At dose level 3 (CPT-11, 100 mg/m2; 5-FU, 500 mg/m 2; and l-LV, 25 mg/body), 2 of 6 patients had DLT (febrile neutropenia and grade 4 neutropenia lasting more than 4 days). To determine whether level 3 was the MTD level, an additional 3 patients were treated at this level, but no DLT was observed. Consequently, 2 of 9 patients had DLT at level 3, this level thus being considered as the RD. At this level, grade 3-4 neutropenia was common but manageable. Nonhematological toxicities were mild. Seven partial responses were observed in the 18 enrolled patients (response rate [RR], 39%), and 8 patients (44%) experienced stable disease. Conclusion. This CPT-11/5-FU/l-LV regimen administered weekly for 3 weeks every 28 days has substantial antitumor activity, with manageable toxicities. A multicenter phase II study is currently underway.

    Original languageEnglish
    Pages (from-to)92-97
    Number of pages6
    JournalInternational Journal of Clinical Oncology
    Volume9
    Issue number2
    DOIs
    Publication statusPublished - Apr 2004

    All Science Journal Classification (ASJC) codes

    • Surgery
    • Hematology
    • Oncology

    Fingerprint

    Dive into the research topics of 'Phase I study of CPT-11 and bolus 5-FU/l-leucovorin in patients with metastatic colorectal cancer'. Together they form a unique fingerprint.

    Cite this