A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer.
Jpn J Clin Oncol
; 48(3): 242-247, 2018 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-29315394
ABSTRACT
BACKGROUND:
The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment.METHOD:
Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed.RESULT:
From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years.CONCLUSION:
Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Vimblastina
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Neoplasias da Mama
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Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
/
Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article