Originally published as JCO Early Release 10.1200/JCO.2005.06.079 on November 30 2004

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Imatinib-Induced Regression of AIDS-Related Kaposi's Sarcoma

Henry B. Koon, Glenn J. Bubley, Liron Pantanowitz, David Masiello, Brad Smith, Katherine Crosby, JoAnn Proper, Will Weeden, Thomas E. Miller, Pamela Chatis, Merrill J. Egorin, Steven R. Tahan, Bruce J. Dezube

From the Beth Israel Deaconess Medical Center; PerkinElmer Life Sciences, Boston; Cell Signaling Technology, Beverly, MA; and University of Pittsburgh Cancer Institute, Pittsburgh, PA

Address reprint requests to Bruce J. Dezube, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave, CC-913, Boston, MA 02215; e-mail: bdezube{at}caregroup.harvard.edu.

PURPOSE: Activation of the platelet-derived growth factor (PDGF) and c-kit receptors has been proposed as important in mediating the growth of AIDS-related Kaposi's sarcoma (KS). We investigated the response of KS to the PDGF receptor (PDGFR)/c-kit inhibitor, imatinib mesylate, and investigated the effect of this therapy on critical signal transduction intermediates.

PATIENTS AND METHODS: Ten male patients with AIDS-related cutaneous KS, which progressed despite chemotherapy and/or highly active antiretroviral therapy, received imatinib mesylate administered orally, 300 mg twice daily. Clinical response was determined by serial tumor measurements. To determine biologic and histologic response, skin lesion biopsies were obtained at baseline and following 4 weeks of therapy.

RESULTS: Five of 10 participants had a partial response by tumor measurements. Biopsies after 4 weeks of therapy demonstrated histologic regression in four of six patients. Four patients' tumor biopsies were assessable for immunohistochemistry end points pre- and post-therapy. These demonstrated inhibition of PDGFR and its downstream effector, extracellular receptor kinase, which is a member of the mitogen-activated protein kinase family. The most common adverse event was diarrhea, which led to dose reduction in six patients.

CONCLUSION: Imatinib mesylate administered orally twice daily for AIDS-related KS results in clinical and histologic regression of cutaneous KS lesions within 4 weeks. These promising results demonstrate that inhibition of the c-kit and/or PDGF receptors may represent an effective strategy for treating KS.

Supported by the AIDS Oncology Clinical Scientist Development Program (H.B.K., grant No. K12CA077846-03).

H.B.K. and G.J.B contributed equally to this work.

Funding for this study was provided by Novartis Pharma AG, Basel, Switzerland.

Presented in part at the International AIDS Malignancy Conference, Bethesda, MD, April 28-29, 2003, and 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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