PURPOSE: A Phase I study of exatecan, a new water-soluble @entity9800 derivative, was conducted to determine the maximum tolerated dose and a recommended dose, according to an internationally standardized core protocol. Pharmacological profiles of @entity13629 and total ( @entity13629 + @entity3338 ) exatecan were also investigated. @entity1 AND METHODS: Fifteen @entity1 with advanced solid @entity5 were treated with 3, 5, and 6.65 mg/m(2) of exatecan infused over 30 min every 3 weeks. Concentrations of @entity13629 , total drug, and a metabolite in plasma and urine were determined during the first course. RESULTS: Dose-limiting @entity1398 and @entity409 were observed in two of six @entity1 at 6.65 mg/m(2), but no grade 3 or worse @entity294 was observed. Emesis was moderate, and no grade 3 or worse @entity390 and @entity391 were observed at a recommended dose of 5 mg/m(2), with prophylactic use of granisetron. Pharmacokinetics were linear and had moderate variability; clearances of @entity13629 and total drug were 6.8 +/- 2.8 and 2.1 +/- 1.1 (mean +/- SD) l/h/m(2), respectively. The ratio of @entity13629 concentration to total drug concentration in plasma decreased from 0.81 +/- 0.06 at the end of infusion to 0.15 +/- 0.06 10 h after the infusion. The @entity13629 :total ratio of drug exposure was 0.30 +/- 0.08, ranging from 0.16 to 0.43. @entity1398 was related to the drug exposure of both @entity13629 and total drug. CONCLUSIONS: The recommended dose of exatecan infused over 30 min every 3 weeks is 5 mg/m(2), with a favorable @entity137 profile of mild and infrequent @entity294 . Interpatient variability of pharmacokinetics was similar to or smaller than that with other @entity9800 derivatives.

Phase I and pharmacological study of a new XXXX derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every three weeks.

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity5 :: ('MESH:D009369', 'Disease') :: ['malignancies'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver dysfunction'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity13629 :: ('CHEBI:25000', 'Chemical') :: ['lactone'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['Neutropenia', 'neutropenia'] @entity9800 :: ('MESH:D002166', 'Chemical') :: ['camptothecin'] @entity3338 :: ('CHEBI:35757', 'Chemical') :: ['carboxylate']
@entity9800 :: (MESH:D002166,Chemical) :: ['camptothecin']
