Phase 1b study of lenvatinib (E7080) in combination with temozolomide for treatment of advanced melanoma.
Oncotarget
; 6(40): 43127-34, 2015 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-26503473
ABSTRACT
OBJECTIVE AND METHODS:
In this phase 1b study, patients with stage 4 or unresectable stage 3 melanoma were treated with escalating doses of lenvatinib (once daily) and temozolomide (TMZ) (days 1-5) in 28-day cycles, to determine the maximum tolerated dose (MTD) of the combination. Dose Level (DL)1 lenvatinib 20 mg, TMZ 100 mg/m2; DL2 lenvatinib 24 mg, TMZ 100 mg/m2; DL3 lenvatinib 24 mg, TMZ 150 mg/m2. Adverse events (AEs) were recorded and tumor response assessed per RECIST 1.0.RESULTS:
Dose-limiting toxicity occurred in 1 of 32 treated patients (DL1); MTD was not reached. The highest dose administered was lenvatinib 24 mg + TMZ 150 mg/m2. Most common treatment-related AEs included fatigue (56.3%), hypertension (53.1%), and proteinuria (46.9%). Overall objective response rate was 18.8% (6 patients), all partial response; (DL1, n = 1; DL3, n = 5). Stable disease (SD) ≥ 16 weeks was observed in 28.1% of patients (DL1 and DL2, n = 1 each; DL3, n = 7); 12.5% of patients had SD ≥ 23 weeks. Single and repeat-dose pharmacokinetics of lenvatinib were comparable across cycles and with concomitant TMZ administration.CONCLUSIONS:
Lenvatinib 24 mg/day + TMZ 150 mg/m2/day (days 1-5) demonstrated modest clinical activity, an acceptable safety profile, and was administered without worsening of either lenvatinib- or TMZ-related toxicities in this patient group.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
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Quinolinas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Dacarbazina
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Melanoma
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article