Preclinical and clinical experience suggests that both retinoids and interferon inhibit HIV replication and have anti-tumor activity against KaposiUs sarcoma (KS). In this study, the combination of interferon- alpha-2b (IFN-a) and 9-cis retinoic acid (9-cRA) will be tested to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy in patients with AIDS-associated KS. A minimum of 6 and a maximum of 24 patients will be studied. Patients will be given 9-cRA (ALRT1057, NSC #659772) at a starting dose of 25 mg/m2/day. No dose escalation of 9-cRA will occur within a designated dose level. The 9-cRA will be given alone for the first 7 days of therapy. Beginning on day 8, patients will be given IFN-a. Patients will be observed at a given dose level for a minimum of four weeks before proceeding to the next dose level. In addition, the study will assess the following in these patients: 1) the levels of the various subtypes of retinoic acid receptor (RAR), retinoid X receptor (RXR), and retinoid orphan receptor (ROR/RZR) mRNA and protein in KS tissue obtained by 2-mm punch biopsy prior to and during therapy with the 9-cRA/IFN-a combination; 2) the pharmacokinetics of 9-cRA and IFN-a; 3) the effects of 9-cRA and IFN-a on HIV activity; and 4) the antitumor effects of 9-cRA and IFN-a.

Project Start
Project End
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
New York University
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016
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