Phase I dose-escalation trial of irinotecan with continuous infusion 5-FU first line, in metastatic colorectal cancer.
AuthorsSaunders, Mark P
Carrington, Bernadette M
Valle, Juan W
AffiliationDepartment of Clinical Oncology, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK. email@example.com
MetadataShow full item record
AbstractThis 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.
CitationPhase 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
JournalBritish Journal of Cancer
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Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.Ingham, S; Warwick, J; Buchan, I; Sahin, S; O'Hara, Catherine; Moran, Anthony; Howell, Anthony; Evans, D; Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UK. (2013-06)Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.
Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council.De Wit, Ronald; Roberts, J Trevor; Wilkinson, Peter M; De Mulder, Pieter H M; Mead, Graham M; Fosså, S D; Cook, P; De Prijck, Linda; Stenning, S; Collette, L; Rotterdam Cancer Institute and University Hospital, Rotterdam, The Netherlands. firstname.lastname@example.org (2001-03-15)PURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles. RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.
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