Phase I dose-escalation study of oral vinflunine administered once daily for 6 weeks every 8 weeks in patients with advanced/metastatic solid tumours.
Cancer Chemother Pharmacol
; 71(3): 647-56, 2013 Mar.
Article
en En
| MEDLINE
| ID: mdl-23299791
ABSTRACT
PURPOSE:
Vinflunine ditartrate is a microtubule inhibitor belonging to the vinca alkaloid family. This phase I study was carried out to evaluate the maximal tolerated dose, the safety profile, the pharmacokinetics and the activity of oral vinflunine (VFL) given daily in patients with advanced/metastatic solid tumours and who have failed standard therapy.METHODS:
Patients were treated with oral VFL administered once daily for 6 weeks followed by a two-week rest. Sequential dose-escalating cohorts of patients were enrolled into 5 dose levels 20, 40, 60, 75 and 95 mg/day.RESULTS:
In total, 27 patients received 53 cycles. Dose-limiting toxicities (DLT) were observed from 60 mg/day. The dose levels 75 and 95 mg/day were both assessed as maximal tolerated dose. The most frequent dose-limiting toxicities were of haematological origin. The recommended dose was defined as 60 mg/day, dose at which 4 patients experienced long stabilizations (≥4 months) and also received longer treatment duration in comparison with the other dose levels. Blood exposure of VFL and its active metabolite 4-O-deacetyl vinflunine (DVFL) increased proportionally to the dose levels. The concentrations of VFL and DVFL reached a steady state at, respectively, 5 and 20 days and remained stable for the rest of the cycle. Increased incidence of DLT/SAE was consistent with the increase of VFL dose and drug exposure.CONCLUSIONS:
These results showed the feasibility of daily oral vinflunine administration on a 6-week treatment duration. This new schedule of administrations enabled sustained and stable blood concentrations of both VFL and DVFL. The recommended dose was defined at 60 mg/day, dose at which 4 patients experienced clinical benefit.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vinblastina
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Inhibidores de la Angiogénesis
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Neoplasias
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Antineoplásicos Fitogénicos
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Francia