A phase I and pharmacologic study of 9-aminocamptothecin administered as a 120-h infusion weekly to adult cancer patients.
Cancer Chemother Pharmacol
; 48(3): 215-22, 2001 Sep.
Article
em En
| MEDLINE
| ID: mdl-11592343
ABSTRACT
PURPOSE:
To define the toxicity profile and the recommended phase II doses of 9-aminocamptothecin (9-AC) administered as a weekly 120-h infusion.METHODS:
9-AC was administered over 120 h weekly to 55 adult cancer patients with solid tumors over doses ranging from 0.41 to 0.77 mg/m2 per day in a phase I and pharmacologic study. 9-AC formulated in dimethylacetamide/polyethylene glycol (DMA) was administered on a 3 of 4-week schedule, and the newer colloidal dispersion (CD) formulation was given on a 2 of 3-week schedule.RESULTS:
Overall, 193 courses of therapy were administered over 122 dose levels. On the 3 of 4-week schedule, 9-AC DMA infused at > or = 0.6 mg/m2 per day for 120 h weekly produced dose-limiting neutropenia, thrombocytopenia, and diarrhea, or resulted in 1-2-week treatment delays. Shortening treatments to 2 of 3 weeks resulted in dose-limiting neutropenia and fatigue at infusion rates > 0.72 mg/m2 per day. The ratio of 9-AC lactone to total (carboxylate + lactone) drug plasma concentrations at steady-state was 0.15 +/- 0.07. Clinical toxicities and drug pharmacokinetics were not substantially different between the DMA and CD formulations. One objective response was observed in a patient with bladder cancer and minor responses were observed in patients with lung and colon cancers. Plasma area under the concentration versus time curve for 9-AC lactone modestly correlated with the degree of thrombocytopenia (r=0.51) using a sigmoid Emax pharmacodynamic model.CONCLUSION:
The recommended phase II dose for the 9-AC DMA formulation is 0.48 mg/m2 per h over 120 h for 3 of 4 weeks and for the 9-AC CD formulation is 0.6 mg/m2 per day over 120 h for 2 of 3 weeks. Both regimens were well tolerated and feasible to administer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos