A Phase 1 clinical trial recently reported in the journal Clinical Cancer Research indicated that the novel drug combination of Velcade (bortezomib) and Zolinza (vorinostat) may be effective in patients with relapsed or refractory myeloma.

Previous preclinical results suggested that Zolinza enhances Velcade’s therapeutic effect. However, this is the first clinical trial to describe the combination of a histone deacetylase (HDAC) inhibitor (Zolinza) and a proteasome inhibitor (Velcade) in heavily pre-treated relapsed or refractory myeloma patients.

The Phase 1 clinical trial monitored 23 patients with relapsed and/or refractory myeloma. In order to be eligible for the trial, patients were required to have received at least three prior regimens. Participants had a median of seven lines of prior treatment, including autologous transplantation, thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade.

Velcade and Zolinza were administered on an outpatient basis. Researchers measured the maximum tolerated dose of Zolinza to be 400 mg daily for eight days every 21-day cycle, with Velcade administered at a dose of 1.3 mg/m² on days one, four, eight, and 11. Patients with less than a partial remission additionally received dexamethasone (Decadron) doses after two cycles.

The overall response rate for the trial was 42 percent, and the response rate among patients who were previously unresponsive to Velcade treatment was 33 percent.

There were no drug-related deaths. The most common grade three or four side effects observed included myelosuppression, fatigue, and diarrhea. These higher level grades indicate severe and potentially life-threatening side effects that affect daily life and require medical attention or hospitalization.

Multicenter Phase 2 and 3 trials have been initiated to further evaluate the combination of Velcade and Zolinza in patients with relapsed or refractory myeloma.

For more information, please see the study published in the journal Clinical Cancer Research (abstract).