Anti-cancer drugs
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Randomized Controlled Trial
A phase I dose-escalation study of edotecarin (J-107088) combined with infusional 5-fluorouracil and leucovorin in patients with advanced/metastatic solid tumors.
Edotecarin (J-107088), a novel inhibitor of topoisomerase I has an additive effect on colon cell lines (HCT-116) when combined with 5-fluorouracil (5-FU). We conducted a phase I study to determine the maximum tolerated dose and recommended a phase II dose of edotecarin in combination with infusional 5-FU/leucovorin (LV) in patients with advanced solid tumors. Patients and cohorts of three to six patients were sequentially enrolled at progressively higher dose levels of edotecarin administered as a 1-h intravenous (IV) infusion every 2 weeks. ⋯ One confirmed complete response in a patient with hepatocellular carcinoma and seven stable disease responses were achieved in the 14 treated patients. Pharmacokinetic analysis showed that edotecarin achieved and maintained apparent steady-state plasma concentrations during the IV administration in both the cycles. The administration of edotecarin in combination with infusional 5-FU/LV once every 14 days, even without the 5-FU bolus, did not permit adequate time for recovery from neutropenia.