Early Trial Evaluates Drug Combo for Blood Cancers

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Researchers at the Massey Cancer Center of Virginia Commonwealth University in Richmond have completed a phase 1 clinical trial evaluating a combination of the drugs Bortezomib and Alvocidib in patients with relapsed or refractory blood cancers. The team, which included contributors from several universities and research institutes, reported its results in the 15 May 2011 issue of the journal Clinical Cancer Research (paid subscription required).

The trial represented the first time a proteasome inhibitor such as Bortezomib was combined with a cell cycle inhibitor such as Alvocidib to treat patients with cancer. Proteasome inhibitors work by blocking the action of proteasomes — large protein complexes that help destroy proteins that are no longer needed by the cell.

Cell cycle inhibitors disrupt the sequence of events that allow cells to undergo cell division and duplication. They also have the ability to block gene transcription, which creates a complementary RNA copy of a DNA sequence.

A phase 1 trial tests an experimental drug for safety, tolerability, and to determine a safe dosage on small numbers of patients. This trial tested the two drugs on 16 patients who had either indolent (non-aggressive) non-Hodgkin’s lymphoma, mantle cell lymphoma, or multiple myeloma. After the patients received the treatments over a 21-day cycle, there were two complete responses, meaning that all detectable traces of the cancer were gone, and five partial responses.

Massy’s co-investigator Beata Holkova says, “Because of the small patient sample size,  we can’t draw definitive conclusions about the effectiveness of the therapy, but we were quite encouraged by the results.”

The researchers are working with the National Cancer Institute on a phase 2 clinical trial to test the effectiveness of this drug therapy. The trial will be conducted with multiple institutions to compare the effectiveness of fixed doses of the drug combination in a larger patient population.

Read more: U.K. Partnership to Test Cancer Drug Combinations

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