Rapid Regression of KS Lesions with Imatinib

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Imatinib Can Produce Rapid Regression of AIDS-Related KS Lesions

By Anne Harding

Feb 25 - Blocking two receptors believed to be involved in the progression of Kaposi's sarcoma (KS) causes clinical and histologic regression of KS lesions in some cases, a new study shows.

Both the platelet-derived growth factor (PDGF) receptor and the c-kit receptor have been implicated in the formation of KS lesions, Dr. Bruce J. Dezube of Beth Israel Deaconess Medical Center in Boston and colleagues note in their report in the February 10 issue of the Journal of Clinical Oncology.

They conducted the current study to determine whether Gleevec (imatinib), currently used to treat chronic myelogenous leukemia and gastrointestinal stromal tumors, might be useful in AIDS-related KS, because the drug is known to be active against both c-kit and PDGF.

Ten patients with AIDS-related KS that had not responded to highly active antiretroviral therapy (HAART) were given 300 mg of Gleevec twice daily for four weeks. Tumor measurements showed a partial response in half of the patients, while tumor biopsies of six patients found histological regression in four.

Of particular interest, immunohistochemistry showed that, in three of the biopsies, treatment resulted in reduced activation of the PDGFR and extracellular receptor kinase (ERK) pathways. ERK is a downstream effector of PDGFR.

"This is really translational science," Dr. Dezube said in an interview with Reuters Health.

The molecular findings of the current study are more important than the clinical ones, he added, particularly as there is already an effective, well-tolerated medication for KS -- Doxil (liposomal doxorubicin) -- taken by thousands of patients. "We almost did it like a proof of principle trial -- we wanted to see if it affected the genes," he explained.

Gleevec, which was given at a higher-than-normal-dose in the current study, was poorly tolerated by patients, with all developing diarrhea. It is not clear, the researchers note, whether this was because the drug interacted with HAART.

The researchers are now conducting a study in 80 KS patients using a 400 mg daily dose of Gleevec to further evaluate efficacy and toxicity of the drug.

J Clin Oncol 2005;23:982-989.

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