The 2009 American Society of Hematology (ASH) Meeting showcased several presentations on Zolinza ^[1] (vorinostat), a histone deacetylase inhibitor developed by Merck Pharmaceuticals that is currently investigated for the treatment of multiple myeloma.

Zolinza alters the way a cancer cell’s DNA creates proteins, which is important in cancer treatment because such a drug can slow down cell proliferation, minimize mutations in DNA and control cell death.

Zolinza With Revlimid And Dexamethasone

Preliminary data from an ongoing Phase 1 study suggest that the combination treatment of Zolinza, Revlimid ^[2] (lenalidomide) and dexamethasone ^[3] (Decadron) is safe and active in relapsed and refractory multiple myeloma patients.

Researchers have enrolled 28 patients with relapsed or refactory myeloma to determine the maximum tolerated dose of the combination treatment. They are also studying the safety and efficacy of the combination treatment.

The participants have received five escalating dosages of Zolinza, Revlimid and dexamethasone for at least eight cycles of treatment.

Twenty five of the 28 enrolled patients have been evaluated with regard to the efficacy of the treatment. Of those 25 patients, 21 (84%) have seen an improvement in their disease. The overall response rate is 64 percent.

Twenty-four patients have experienced at least one side effect, with the most common being diarrhea, fatigue, neutropenia (low white blood cell count) and thrombocytopenia (low platelet count).

One dose-limiting toxicity has been observed at the highest dose level. Six additional patients were escalated to that dose level. No additional dose-limiting toxicities have been observed since then. The maximum tolerated dose has therefore not been reached yet.

Researchers continue to investigate the combination treatment to further evaluate the efficacy and safety of this treatment.

Zolinza With Doxil And Velcade

Results from another Phase 1 study that was presented at the ASH meeting show that Zolinza in combination with Doxil ^[4] (pegylated liposomal doxorubicin) and Velcade ^[5] (bortezomib) is safe and efficacious in patients with relapsed and refractory multiple myeloma.

Nine patients (median age of 56) with relapsed or refractory myeloma enrolled in this study, receiving 1.3mg/m² of Velcade on days 1, 4, 8, and 11, and 30mg/m² of Doxil on day 4 of treatment. In addition, they were given escalating doses of Zolinza once daily on days 4 through 11 of a 3-week cycle. Three patients received 200 mg of Zolinza, four received 300 mg and two were given 400 mg.

Six out of seven evaluable patients responded to the treatment. One patient experienced a complete response, one patient went into very good partial remission and the remaining four experienced partial remission.

Common side effects included fatigue, diarrhea, nausea, vomiting and peripheral neuropathy (nerve damage in the extremities that can cause pain and tingling sensations). Three patients required dose reductions due to the side effects.

Blood-related side effects included neutropenia (low white blood cell count), lymphopenia (low lymphocyte count), and thrombocytopenia (low platelet count).

Researchers point out that they will have to consider side effects when determining the optimal dose for the Phase 2 study.

Zolinza With Velcade

Preliminary results from an ongoing Phase 1 trial suggest that extended treatment of Velcade in combination with Zolinza shows long-term activity in patients with relapsed and refractory myeloma.

The study sequentially enrolled 34 patients with relapsed or refractory multiple myeloma. They received escalating doses of Zolinza (200 or 400 mg) for at least eight treatment cycles. Plus, they either were given 0.7 or 0.9 mg/m2 of Velade on days 4, 8, 11 and 15, or 0.9, 1.1 or 1.3 mg/m2 of Velcade on days 1, 4, 8 and 11. Patients received 20 mg of oral dexamethasone (Decadron) on days 1-4 and 9-12 of each cycle if their disease progressed.

Nine patients have completed the study through twelve or more treatment cycles so far. Of these nine patients, five patients have experienced a partial response, two have had a minimal response, and two have been given the diagnosis of a stable disease.

All of the nine patients experienced mild to moderate side effects, most commonly diarrhea, nausea and fatigue.

Seven out of the nine patients have discontinued the treatment because their disease has progressed. The median time to progression was 294 days.

Based on these preliminary results, the study authors feel that the Zolinza/Velcade combination treatment could provide long-term responses to relapsed/refractory myeloma patients.

For more information, see abstracts 305 ^[6], 306 ^[7], and 3386 ^[8] at the ASH meeting Web site.