Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study.
Br J Cancer
; 111(11): 2058-66, 2014 11 25.
Article
em En
| MEDLINE
| ID: mdl-25290090
ABSTRACT
BACKGROUND:
This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine.METHODS:
Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an 'up-down' design to determine the toxicity contour of the combination.RESULTS:
Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m(-2) twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients.CONCLUSIONS:
In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias
Tipo de estudo:
Clinical_trials
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:
2014
Tipo de documento:
Article