Title: A phase I study with MAG-camptothecin intravenously administered weekly for 3 weeks in a 4-week cycle in adult patients with solid tumours
Authors: Wachters, F M ×
Groen, H J M
Maring, J G
Gietema, J A
Porro, M
Dumez, Herlinde
de Vries, E G E
van Oosterom, A T #
Issue Date: Jun-2004
Series Title: British Journal of Cancer vol:90 issue:12 pages:2261-7
Abstract: In MAG-camptothecin (MAG-CPT), the topoisomerase inhibitor camptothecin is linked to a water-soluble polymer. Preclinical experiments showed enhanced antitumour efficacy and limited toxicity compared to camptothecin alone. Prior phase I trials guided the regimen used in this study. The objectives were to determine the maximum tolerated dose, dose-limiting toxicities, safety profile, and pharmacokinetics of weekly MAG-CPT. Patients with solid tumours received MAG-CPT intravenously administered weekly for 3 weeks in 4-week cycles. At the starting dose level (80 mg x m(-2) week(-1)), no dose-limiting toxicities occurred during the first cycle (n=3). Subsequently, three patients were enrolled at the second dose level (120 mg x m(-2) week(-1)). Two of three patients at the 80 mg x m(-2) week(-1) cohort developed haemorrhagic cystitis (grade 1/3 dysuria and grade 2/3 haematuria) during the second and third cycles. Next, the 80 mg x m(-2) week(-1) cohort was enlarged to a total of six patients. One other patient at this dose level experienced grade 1 haematuria. At 120 mg x m(-2) week(-1), grade 1 bladder toxicity occurred in two of three patients. Dose escalation was stopped at 120 mg x m(-2) week(-1). Cumulative bladder toxicity was dose-limiting toxicity at 80 mg x m(-2) week(-1). Pharmacokinetics revealed highly variable urinary camptothecin excretion, associated with bladder toxicity. Due to cumulative bladder toxicity, weekly MAG-CPT is not a suitable regimen for treatment of patients with solid tumours.
ISSN: 0007-0920
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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