According to the results of a Phase 1/2 clinical trial, Torisel in combination with Velcade was well tolerated and effective for the treatment of relapsed/refractory multiple myeloma.

Dr. Irene Ghobrial of the Dana-Farber Cancer Institute presented the results at the 2010 annual American Society of Hematology (ASH) conference held in Orlando last month.

Dr. Ghobrial said the trial results were promising in heavily pretreated myeloma patients and that the combination of Torisel (temsirolimus) and Velcade (bortezomib) warrants further evaluation.

Torisel is marketed by Pfizer and is currently approved for the treatment of advanced kidney cancer. It works by inhibiting a protein essential for cancer cell growth and division.  A previous study showed that the overall response rate with Torisel alone is 43 percent in myeloma patients.

This study was designed to determine the safety and efficacy of Torisel in combination with Velcade in previously treated myeloma patients.  Phase 1 of the study included 20 patients, and Phase 2 included 43 patients.  Most participants were heavily pre-treated, and 63 percent had relapsed or were resistant (refractory) to their last Velcade treatment.

In Phase 1 of the trial, patients received 1.3 or 1.6 mg/m² Velcade weekly for 4 out of 5 weeks as well as 15 or 25 mg Torisel weekly.  Both drugs were tolerated at the maximum doses tested.

In Phase 2 of the trial, 47 percent of patients responded to treatment, which included 5 percent complete responses, 9 percent very good partial responses, 19 percent partial responses, and 14 percent minimal responses. Two-thirds of patients who had previously been treated with Velcade achieved stable disease, and 20 percent achieved a minimal response or better.

“If we had used twice-a-week Velcade instead of once-a-week Velcade or added dexamethasone [Decadron] in this combination, potentially we could have had an even higher response in [Velcade-refractory] patients,” said Dr. Ghobrial.

Progression-free survival was 5.6 months, and overall survival was 18.8 months.

Almost all patients experienced side effects, especially low platelet counts, which were associated with both Velcade and Torisel. Other types of low blood cell counts were common as well.

Of note, 34 percent of participants experienced peripheral neuropathy (tingling in the arms and legs), but there were no reported cases of severe peripheral neuropathy in this study.  Dr. Ghobrial hypothesized that the reduced peripheral neuropathy in this study compared to what is normally seen with Velcade administration may have been due to the once-weekly dose of Velcade or a protective effect conferred by Torisel.

For more information, see abstract 990 on the ASH annual meeting website.