A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas
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A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas. / Vitfell-Rasmussen, Joanna; Judson, Ian; Safwat, Akmal Ahmed; Jones, Robin L; Rossen, Philip Blach; Lind-Hansen, Maja; Knoblauch, Poul; Krarup-Hansen, Anders.
I: Sarcoma, Bind 2016, 2090271, 2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas
AU - Vitfell-Rasmussen, Joanna
AU - Judson, Ian
AU - Safwat, Akmal Ahmed
AU - Jones, Robin L
AU - Rossen, Philip Blach
AU - Lind-Hansen, Maja
AU - Knoblauch, Poul
AU - Krarup-Hansen, Anders
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1155/2016/2090271
DO - 10.1155/2016/2090271
M3 - Journal article
C2 - 27403082
VL - 2016
JO - Sarcoma
JF - Sarcoma
SN - 1357-714X
M1 - 2090271
ER -
ID: 179160778