Background. Belinostat is a novel histone deacetylase inhibitor. Primary Objectives. Maximum tolerated dose (MTD) and dose\nlimiting toxicities (DLTs) of belinostat (Bel) in combination with doxorubicin (Dox) in solid tumours (phase I) and response rate\n(RR) in soft tissue sarcomas (phase II). Methods. Bel was administered as a 30-minute IV infusion on days 1ââ?¬â??5 and on day 5with Dox.\nThe dose escalation schedule was as follows: cohort 1: Bel 600mg/m2 and 50mg/m2 Dox, cohort 2: Bel 600mg/m2 and 75mg/m2\nDox, cohort 3: Bel 800mg/m2 and 75mg/m2 Dox, and cohort 4: Bel 1000mg/m2 and 75mg/m2 Dox. Results. 41 patients were\nincluded (25 in phase I, 16 in phase II). Adverse events were fatigue (95%), nausea (76%), and alopecia (63%). There was one DLT,\ngrade 3 rash/hand and foot syndrome. MTD was Bel 1000 mg/m2/d and Dox 75mg/m2. Four responses were seen: 2 PR in phase\nI, 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.\nResponse rate was moderate but median time to progression was 6.0 months (95% CI, 1.6ââ?¬â??9.7 months) which is superior to some\nreports of single-agent Dox.
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