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Phase II AIDS Malignancy Consortium (AMC) trial of topical halofuginone in AIDS-associated Kaposi’s sarcoma (KS): clinical and biological effects using a novel intra-patient control design


KS is a disease of multifocal vascular proliferation. Matrix metalloproteinases (MMPs) and type I collagen play critical roles in angiogenesis and are potential targets. Halofuginone (Tempostatin™), a synthetic quinazolinone alkaloid derivative, induced anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. It inhibits several essential stages of angiogenesis: endothelial cell proliferation, MMP2 expression, BM invasion, ECM deposition by newly formed vessels, synthesis of type I collagen during angiogenic sprouting, and bFGF-induced neovascularization. These data suggested that halofuginone might have activity in KS.


The AMC developed a novel trial design with a blinded intra-patient vehicle control. Halofuginone was supplied by Collgard Biopharmaceuticals Ltd (Atlanta, GA) to the NCI-DCTD under a CRADA as a 0.01% w/w ointment. Twelve KS lesions were divided into two groups of six, designated Group A and Group B. Tubes designated A and B containing either halofuginone or matching placebo ointment were supplied in a blinded fashion. Ointment A was applied to Group A lesions and ointment B to Group B lesions twice daily. Lesion response was assessed every 4 weeks for Group A and Group B lesions individually, and global response assessed both treated and untreated disease. Tumor biopsies obtained at baseline and from both Group A and B lesions during treatment were studied for expression of type I collagen by ISH and of MMP2 and VEGF by IHC. A patient subset had blood sampling after 8 weeks to evaluate systemic absorption.


Twenty-three patients were treated. Median CD4 count was 322 (2-693); 68% had undetectable HIV RNA. Treatment was well tolerated. Of 14 patients who completed 12 weeks of treatment, 26% (95% CI, 10%-48%) showed partial response in halofuginone-treated lesions and 17% in placebo-treated lesions (95% CI, 5%-39%), (P=0.689). Global response was 30% (95% CI, 13%-53%). None of 10 subjects showed detectable blood levels. Type 1 collagen message decreased significantly in halofuginone-treated lesions at week 4, whereas vehicle-treated lesions showed no change. VEGF protein expression decreased significantly in vehicle-treated lesions at week 4, whereas halofuginone-treated lesions showed no change. There were no differences in levels of MMP2 or VEGF protein between halofuginone- and vehicle-treated lesions. No changes in HIV RNA levels or CD4 counts were observed.


Although topical halofuginone appears ineffective for KS treatment, this study presents a novel design that could be applied to future studies using the patient as his own control to test a topical, non-absorbed agent.


This work was supported by UO1 CA121947.

This article has been published as part of Infectious Agents and Cancer Volume 5 Supplement 1, 2010: Proceedings of the 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI).The full contents of the supplement are available online at

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Correspondence to Susan E Krown.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Krown, S.E., Fingleton, B., Lee, J.Y. et al. Phase II AIDS Malignancy Consortium (AMC) trial of topical halofuginone in AIDS-associated Kaposi’s sarcoma (KS): clinical and biological effects using a novel intra-patient control design. Infect Agents Cancer 5 (Suppl 1), A62 (2010).

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