Lassen, U., Molife, L. R., Sorensen, M., Engelholm, S., Vidal, L., Sinha, R., Penson, R. T., Buhl-Jensen, P., Crowley, E., Tjornelund, J., Knoblauch, P., de Bono, J. S. (2010) A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. BRITISH JOURNAL OF CANCER, 103 (1). pp. 12-17. ISSN 0007-0920

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Abstract

BACKGROUND: This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours. METHODS: Cohorts of three to six patients were treated with escalating doses of belinostat administered intravenously once daily, days 1-5 q21 days; on day 3, carboplatin (area under the curve (AUC) 5) and/or paclitaxel (175 mgm(-2)) were administered 2-3 h after the end of the belinostat infusion. RESULTS: In all 23 patients received 600-1000 mgm(-2) per day of belinostat with carboplatin and/or paclitaxel. No DLT was observed. The maximal administered dose of belinostat was 1000 mgm(-2) per day for days 1-5, with paclitaxel (175 mgm-2) and carboplatin AUC 5 administered on day 3. Grade III/IV adverse events were (n; %): leucopenia (5; 22%), neutropenia (7; 30%), thrombocytopenia (3; 13%) anaemia (1; 4%), peripheral sensory neuropathy (2; 9%), fatigue (1; 4%), vomiting (1; 4%) and myalgia (1; 4%). The pharmacokinetics of belinostat, paclitaxel and carboplatin were unaltered by the concurrent administration. There were two partial responses (one rectal cancer and one pancreatic cancer). A third patient (mixed mullerian tumour of ovarian origin) showed a complete CA-125 response. In addition, six patients showed a stable disease lasting >= 6 months. CONCLUSION: The combination was well tolerated, with no evidence of pharmacokinetic interaction. Further evaluation of anti-tumour activity is warranted. British Journal of Cancer (2010) 103, 12-17. doi:10.1038/sj.bjc.6605726 www.bjcancer.com Published online 15 June 2010 (C) 2010 Cancer Research UK

Item Type:	Article
Authors (ICR Faculty only):	De-Bono, Johann
All Authors:	Lassen, U., Molife, L. R., Sorensen, M., Engelholm, S., Vidal, L., Sinha, R., Penson, R. T., Buhl-Jensen, P., Crowley, E., Tjornelund, J., Knoblauch, P., de Bono, J. S.
Uncontrolled Keywords:	HDAC; belinostat; carboplatin; paclitaxel; BelCaP;TOPOISOMERASE-II; TRIAL; CANCER; VORINOSTAT; PXD101; ACID
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group
Depositing User:	Users 10 not found.
Date Deposited:	20 Jul 2010 08:24
Last Modified:	11 Jul 2017 10:02
URI:	http://publications.icr.ac.uk/id/eprint/9754

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