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    Phase I dose-escalation trial of irinotecan with continuous infusion 5-FU first line, in metastatic colorectal cancer.

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    Authors
    Saunders, Mark P
    Hogg, M
    Carrington, Bernadette M
    Sjursen, Ann-Marie
    Allen, J
    Beech, Janette
    Swindell, Ric
    Valle, Juan W
    Affiliation
    Department of Clinical Oncology, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK. mark.saunders@christie-tr.nwest.nhs.uk
    Issue Date
    2004-10-18
    
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    Abstract
    This single-centre phase I trial was designed to determine the maximum tolerated dose of irinotecan and the recommended dose to use in combination with a fixed dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for the first-line treatment of metastatic colorectal cancer (CRC). Tolerability and efficacy were secondary end points. In all, 22 patients, median age 57 years, were treated with escalating, weekly doses of irinotecan (50, 75, 100 and 85 mg m(-2)) in combination with 250 mg m(-2) 5-FU administered as a continuous infusion. All patients had measurable disease. The combination was well tolerated up to an irinotecan dose of 75 mg m(-2). However, three out of five patients at the 100 mg m(-2) irinotecan dose level had their dose reduced due to multiple grade 2 toxicities, and eventually one patient stopped treatment due to grade 3 diarrhoea and multiple grade 2 toxicities. Subsequent patients were recruited at an irinotecan dose level of 85 mg m(-2). The overall response rate was 55%, comprising one complete and 11 partial responses (PRs). Six patients also achieved sustained stable disease (SD), giving a clinical benefit (complete response/PR/SD) response of 82%. The median duration of response was 238 days (8.5 months) and median time to progression was 224 days (8.0 months). Two patients who achieved PRs underwent partial hepatectomies. Thus, irinotecan (85 mg m(-2)) combined with a continuous infusion of 5-FU (250 mg m(-2)) is an active and well-tolerated regimen for the treatment of metastatic CRC. It represents an effective treatment for patients who require close supervision and support, throughout their initial exposure to chemotherapy for this disease, and this dose combination was recommended for an ongoing phase II study.
    Citation
    Phase I dose-escalation trial of irinotecan with continuous infusion 5-FU first line, in metastatic colorectal cancer. 2004, 91 (8):1447-52 Br. J. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/77841
    DOI
    10.1038/sj.bjc.6602173
    PubMed ID
    15452550
    Type
    Article
    Language
    en
    ISSN
    0007-0920
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.bjc.6602173
    Scopus Count
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