A Phase I, open-label, dose-escalation study of continuous once-daily oral treatment with afatinib in patients with advanced solid tumors.
Invest New Drugs
; 31(2): 409-16, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23242861
ABSTRACT
BACKGROUND:
This trial evaluated the safety, tolerability and maximum tolerated dose (MTD) of afatinib, a novel ErbB Family Blocker.METHODS:
In this open-label, dose-escalation Phase I study, afatinib was administered continuously, orally, once-daily for 28 days to patients with advanced or metastatic solid tumors. Dose escalation was performed in a 3 + 3 design, with a starting dose of 10 mg/day (d); doses were doubled for each successive cohort until the MTD was defined. The MTD cohort was expanded to a total of 19 patients. Incidence and severity of adverse events (AEs), antitumor activity and pharmacokinetics were assessed.RESULTS:
Thirty patients received at least one dose of afatinib. Twenty-nine patients were evaluable for response. Dose-limiting toxicities (DLTs) consisting of Grade 3 diarrhea were observed in two out of three patients treated at 60 mg/d. The MTD was determined at 40 mg/d. The most frequent treatment-related AEs were diarrhea and mucosal inflammation reported in 76.7% and 43.3% of patients respectively. Five patients had stable disease with a median progression-free survival of 111 days. No objective responses occurred. Pharmacokinetic data showed no deviation from dose-proportionality and steady-state was reached on Day 8 at the latest.CONCLUSIONS:
Afatinib was well tolerated with manageable side effects when administered once-daily, continuously at a dose of 40 mg.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Neoplasias
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article