TopoTaget A S
TopoTaget A S
Lassen U.,Copenhagen University |
Molife L.R.,Royal Marsden Hospital |
Sorensen M.,Copenhagen University |
Engelholm S.-A.,Copenhagen University |
And 8 more authors.
British Journal of Cancer | Year: 2010
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 mg m 2) were administered 2-3 h after the end of the belinostat infusion.Results:In all 23 patients received 600-1000 mg m 2 per day of belinostat with carboplatin and/or paclitaxel. No DLT was observed. The maximal administered dose of belinostat was 1000 mg m 2 per day for days 1-5, with paclitaxel (175 mg m 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. © 2010 Cancer Research UK All rights reserved.