High-dose vorinostat is effective in relapsed lymphomas

Patients whose aggressive lymphomas have relapsed or failed to respond to the current front-line chemotherapy regimen now have an effective second line of attack against their disease. High doses of vorinostat (suberoylanilide hydroxamic acid) in combination with another round of commonly used second-line drugs produced a 70% response rate in patients, including complete elimination of lymphoma cells in several patients.

Lymphoma refers to a group of cancers that strike the lymphatic system, which is a key part of the immune system. Lymphomas are broadly classified as either Hodgkin or non-Hodgkin. Some lymphomas are highly curable; others require complex treatment.

This study's results open the way to potentially solve the dilemma of how to effectively treat patients when modern cancer drugs fail after the first try. Corresponding author Ajay Gopal, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, said these findings set the stage for using a new class of drugs called histone deacetylase inhibitors (HDAC), of which vorinostat is one, to sensitize tumor cells to the cancer-killing effects of chemotherapy.

This first-of-its-kind phase I clinical trial tested the effectiveness of HDACs to augment standard chemotherapy. Patients treated in the trial had several types of lymphoma. The best responses were seen in those with Hodgkin and diffuse large B-cell lymphomas, which are two of the most aggressive types and typically require a stem cell transplant when first-line treatment is not curative. Knocking back the cancer increases the likelihood of a successful transplant. This study was published in the British Journal of Haematology (2013; doi:10.1111/bjh.12230).

The researchers noted that while the current front-line chemotherapy drugs are the most effective yet against lymphomas, patients who relapse after receiving them are less likely to achieve long-term, disease-free survival when current second-line or salvage therapies are applied. This is because the cancers develop resistance to the drugs or the tumor's biology changes in some way to reduce their effectiveness.

Preclinical studies have found vorinostat to be effective when used along with the standard chemotherapy combination (R)ICE (rituximab, ifosphamide, carboplatin, and etoposide). Vorinostat works by blocking signals to tumor-suppressor genes, which allows those genes to induce tumor cell death.

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