Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

KAPOSI'S SARCOMA: BIOLOGIC THERAPY WITH INTERFERONS AND RETINOIDS

S.E. Krown
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.6
AIDS 1994, Vol. 8 (Suppl. 4);S12

Interferon-α (IFN-α), although widely used to treat Kaposi's sarcoma (KS) in HIV-infected individuals for over a decade, has only recently been recognized as a potential inhibitor of angiogenic cytokines and growth factors believed to play a central role in KS pathogenesis. For example, low-dose IFN-α given to normal volunteers and patients with hepatitis C induced increased circulating levels of the interleukin-1 receptor antagonist (IL-1Ra). In addition, IFNs α and β have been shown to down-regulate the expression of basic fibroblast growth factor (bFGF) in a variety of human carcinoma cell lines at the mRNA and protein levels, an effect that was independent of inhibition of cell proliferation. A number of clinical studies have now confirmed the high response rates for the combination of IFN-α and zidovudine (AZT) noted in earlier phase I trials. These studies have not only documented activity for relatively low doses of IFN-α (compared to those used as monotherapy) when combined with AZT, but have also confirmed a relatively high degree of antitumor activity in patients with CD4 counts below 200/μl, who rarely respond to high doses of IFN alone. An ongoing study of the IFN-α/ddI combination has also shown antitumor activity for IFN-α doses as low as 1 million U/d. Retinoids, both alone and in combination with IFN-α are also under study for KS, and may also function as cytokine modulators. In clinical trials, however, differential effects on KS growth, including apparent tumor stimulation at high doses, have been noted, with the best responses reported after relatively low doses of trans-retinoic acid. These results and others lend credence to the concept of KS as a cytokine-driven proliferative process whose course may be modified by biologic agents.

Presenting author: S.E. Krown

1994-11-18
13.6

Originally published in AIDS Volume 8, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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