A Clinical Phase I / II Trial of Belinostat in Combination With Erlotinib in Patients With Non-small Cell Lung Cancer
Belinostat, developed by CuraGen, belongs to a new class of hydroxymat-type histone
deacetylase (HDAC) inhibitors. HDAC inhibitors, including Belinostat, has shown marked in
vitro and in vivo activity against a number of solid tumors and hematological cancers.
Belinostat has proven to be effective as a single agent or in combination with other
anticancer agents such as doxorubcin, paclitaxel, carboplatin, fluorouracil, bortezumib, and
there has been observed synergy between Belinostat or other HDAC inhibitors and EGFR
inhibitors gefinitinib and erlonitib.
Furthermore, the antineoplastic activity of Belinostat seen in preclinical experiments have
resulted in only moderate toxicity.
In the two Phase I trials of Belinostat for solid tumors and hematological malignancies
Belinostat have been well tolerated at doses up to 2000 mg daily in more than 100 patients.
Fatigue, nausea and vomiting has been the main side effects and with none or very mild
hematologic toxicity. Approximately 25% of patients in the study of solid tumors achieved
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary purpose of the phase I part of the trial is to establish the tolerance dose (maximum tolerated dose (MTD) and dose limiting toxicity (DLT).
Jon L Andersen, MD
Dept of Oncology Copenhagen University Hospital Herlev
Denmark: Danish Medicines Agency