A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas.

ABSTRACT: Background. Belinostat is a novel histone deacetylase inhibitor. Primary Objectives. Maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of belinostat (Bel) in combination with doxorubicin (Dox) in solid tumours (phase I) and response rate (RR) in soft tissue sarcomas (phase II). Methods. Bel was administered as a 30-minute IV infusion on days 1-5 and on day 5 with Dox. The dose escalation schedule was as follows: cohort 1: Bel 600?mg/m(2) and 50?mg/m(2) Dox, cohort 2: Bel 600?mg/m(2) and 75?mg/m(2) Dox, cohort 3: Bel 800?mg/m(2) and 75?mg/m(2) Dox, and cohort 4: Bel 1000?mg/m(2) and 75?mg/m(2) Dox. Results. 41 patients were included (25 in phase I, 16 in phase II). Adverse events were fatigue (95%), nausea (76%), and alopecia (63%). There was one DLT, grade 3 rash/hand and foot syndrome. MTD was Bel 1000?mg/m(2)/d and Dox 75?mg/m(2). Four responses were seen: 2 PR in phase I, RR of 8%; in phase II, 1 PR/1 CR, RR of 13%, and 9 patients (56%) with SD. Conclusion. The combination was well tolerated. Response rate was moderate but median time to progression was 6.0 months (95% CI, 1.6-9.7 months) which is superior to some reports of single-agent Dox.

SUBMITTER: Vitfell-Rasmussen J 

PROVIDER: S-EPMC4923583 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature