Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study
Isakoff, S J
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CitationIsakoff, S J, D Wang, M Campone, A Calles, E Leip, K Turnbull, N Bardy-Bouxin, L Duvillié, and E Calvo. 2014. “Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study.” British Journal of Cancer 111 (11): 2058-2066. doi:10.1038/bjc.2014.508. http://dx.doi.org/10.1038/bjc.2014.508.
AbstractBackground: 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.
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