Relapsed/Refractory Patients:

Zolinza® (vorinostat)

What is Zolinza?

Zolinza (vorinostat) is a histone deacetylase (HDAC) inhibitor. Some cancer cells display excess HDAC activity, which inhibits the expression of genes that regulate cell growth. In laboratory studies, Zolinza has been shown to inhibit cancer cell growth and to induce cell death.

Zolinza is made by Merck and is FDA approved for the treatment of a type of cancer known as cutaneous T-cell lymphoma (CTLC). Other names for Zolinza are SAHA (suberoylanilide hydroxamic acid) and MK0683. Zolinza is an oral drug that is taken once a day with food.

What do we know about Zolinza’s activity in myeloma?

Laboratory and animal studies show that Zolinza displays additive, and often synergistic, activity when combined with Velcade® (bortezomib), melphalan, or Revlimid® (lenalidomide) and dexamethasone. In addition, adding Zolinza to agents such as Velcade, Revlimid, or Thalomid® (thalidomide) has resulted in responses to these agents in relapsed/refractory myeloma.

Several phase I studies have been conducted with Zolinza in relapsed and/or refractory myeloma. Preliminary data show that:

• The combination of Zolinza and Velcade appears to be active over the long term, even in some patients who have previously received Velcade and stopped responding.
• The combination of Zolinza, Revlimid, and dexamethasone appears to be an active oral regimen that is well tolerated.
• Adding Zolinza to Velcade and Doxil appears to be efficacious, and the toxicities manageable in an ongoing study.

The combination of Zolinza and Velcade is being evaluated in Phase II and III trials in relapsed and/or refractory myeloma.

• Interim results of a Phase IIb study evaluating the combination in patients with relapsed and refractory myeloma suggest that it is effective in Velcade-refractory myeloma. This trial (Vantage 095) is being facilitated by the Multiple Myeloma Research Consortium (MMRC). Preliminary findings were presented on the first 108 patients, who were heavily pretreated with a median of five prior treatments, and could receive dexamethasone if they had a less than optimal response. Final results of this study are expected in 2011.
• The combination of Zolinza and Velcade is being compared to Velcade alone in a Phase III trial known as Vantage 088. Enrollment in this trial has been completed, and includes patients who have received 1 to 3 previous therapies.

Zolinza is also being evaluated in newly diagnosed myeloma.

• Preliminary results of an ongoing Phase I trial of Zolinza, Revlimid, Velcade and dexamethasone show promising early efficacy, and no unexpected side effects have been noted.

How is Zolinza currently being studied in myeloma?

Zolinza is being studied in a number of clinical trials in relapsed and/or refractory myeloma, including:

• A Phase I/II trial in combination with carfilzomib, Revlimid, and dexamethasone (QUAD), which is set to begin
• A Phase I study in combination with Velcade and Doxil

In addition, Zolinza is being evaluated as maintenance therapy in patients who have undergone autologous stem cell transplant:

• A Phase II trial in combination with Velcade
• A Phase I trial in combination with Revlimid

Zolinza is also being evaluated in a Phase I trial in newly diagnosed myeloma in combination with Revlimid, Velcade, and dexamethasone.

To find a clinical trial, call 1-866-603-MMCT (-6628) or click here to go to the MMRF Patient Navigator Program.