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Phase I trial of vinflunine and pemetrexed in refractory solid tumors.
Sanoff, Hanna K; Davies, Janine; Walko, Christine; Buie, Larry; Chiu, Wing-Keung; Ivanova, Anastasia; O'Neil, Bert; Stinchcombe, Thomas E; Keller, Kimberly; Dees, E Claire.
Afiliación
  • Sanoff HK; Department of Medicine, Division of Hematology-Oncology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. hsanoff@virginia.edu
Invest New Drugs ; 29(1): 131-6, 2011 Feb.
Article en En | MEDLINE | ID: mdl-19830387
ABSTRACT

BACKGROUND:

Vinflunine is a novel vinca alkaloid with promising single agent clinical activity. Pemetrexed has at least additive activity with other vincas. A phase I trial was undertaken to assess the safety of vinflunine and pemetrexed in patients with refractory solid tumors.

METHODS:

A standard 3-patient cohort dose escalation scheme was used to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the vinflunine/pemetrexed combination. Pemetrexed 500 mg/m(2) was given with vinflunine 280 mg/m(2) (cohort 1), 300 mg/m(2) (cohort 2) or 320 mg/m(2) (cohort 3) on day 1 of a 21-day cycle.

RESULTS:

19 patients were enrolled, median age 58 years (range 32 to 77) and had a median of 3 (range 1-6) prior therapies. DLT occurred 1 of 6 pts in cohort 1 (thrombocytopenia, hyponatremia), 2 of 10 pts in cohort 2 (febrile neutropenia, hyponatremia, hyperbilirubinema; febrile neutropenia), and 2 of 3 pts in cohort 3 (febrile neutropenia, hypokalemia; febrile neutropenia). 1 pt in cohort 2 died prior to completion of cycle 1 likely from disease progression. Most common grade 3/4 adverse events were neutropenia (7), leukopenia (5). Febrile neutropenia occurred in 4 patients (21%). No objective responses were seen. Two patients (breast and lung) had prolonged stable disease for 25 and 20 cycles respectively.

CONCLUSIONS:

Based on this experience we recommend vinflunine 300 mg/m(2) and pemetrexed 500 mg/m(2) in combination every 3 weeks for future study. At these doses, the combination of vinflunine and pemetrexed was tolerable in this heavily pretreated population. Hematologic toxicity, including febrile neutropenia, was prominent.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Vinblastina / Protocolos de Quimioterapia Combinada Antineoplásica / Resistencia a Antineoplásicos / Glutamatos / Guanina / Neoplasias / Antineoplásicos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Invest New Drugs Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Vinblastina / Protocolos de Quimioterapia Combinada Antineoplásica / Resistencia a Antineoplásicos / Glutamatos / Guanina / Neoplasias / Antineoplásicos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Invest New Drugs Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos