title: 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.
authors.affiliation: Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
authors.forename: Joanna
authors.identifier: 0000-0003-0983-0732
authors.initials: J
authors.lastname: Vitfell-Rasmussen
authors.affiliation: The Institute of Cancer Research: Royal Cancer Hospital, 123 Old Brompton Road, London SW7 3RP, UK.
authors.forename: Ian
authors.identifier: 0000-0002-4766-5304
authors.initials: I
authors.lastname: Judson
authors.affiliation: Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus, Denmark.
authors.forename: Akmal
authors.identifier: 0000-0002-6020-2320
authors.initials: A
authors.lastname: Safwat
authors.affiliation: The Institute of Cancer Research: Royal Cancer Hospital, 123 Old Brompton Road, London SW7 3RP, UK.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.affiliation: Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus, Denmark.
authors.forename: Philip Blach
authors.initials: PB
authors.lastname: Rossen
authors.affiliation: Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
authors.forename: Maja
authors.initials: M
authors.lastname: Lind-Hansen
authors.affiliation: Onxeo, c/o Symbion, Fruebjergvej 3, 2100 København, Denmark.
authors.forename: Poul
authors.initials: P
authors.lastname: Knoblauch
authors.affiliation: Herlev University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
authors.forename: Anders
authors.identifier: 0000-0002-0200-4086
authors.initials: A
authors.lastname: Krarup-Hansen