|S.A. Miles, University of California-Los Angeles CARE Center, presented interim data on 66 patients treated openly with 9-cis retinoic acid (9-CRA). All of the AIDS Kaposi's sarcoma (AKS) patients entered free of opportunistic infections. Daily oral doses of 9-CRA at 60 to 100 mg led to an overall response rate (RR) of 37%. Adverse drug events (ADEs) included headache (26%), elevated triglycerides (18%), and decreased neutrophils (16%). HIV ribonucleic acid (RNA) levels did not change significantly using 9-CRA with antiviral drugs.|
|Introduction to open Phase II study||Retinoids block in vitro multiplication of cells derived from AKS. Both 9-CRA and all-trans retinoic acid (ATRA) selectively inhibit AKS cells; however, topical and oral studies show 9-CRA to have better profiles for bioavailability and pharmacodynamics compared with ATRA.|
|Methodology||Fourteen US clinical centers enrolled 66 AKS patients free of secondary
opportunistic infections. Baseline history included prior local therapy
by 47% and various systemic chemotherapies or immunotherapy by 48% of the
patients, respectively. The most frequently used concurrent antiviral
drug was 3TC (82%) followed by D4T (48%) and AZT (40%).
Oral dosing with 9-CRA began at 60 mg/msq each afternoon. If tolerated, the dose could be increased to 100 mg/msq. Patients reported biweekly to the clinic for CD4 T lymphocyte counts, HIV RNA estimation, and ADEs. Evaluation of the tumor response took place after 16 weeks' 9-CRA therapy in 52 patients.
|Therapeutic effects with 9-CRA||
Fifty-two patients, treated for at least 16 weeks, showed the following
At baseline, HIV RNA averaged 190,000 copies/mL even though 76% of the patients had been receiving 3 or 4 antiviral drug regimens. HIV RNA levels did not change significantly during added 9-CRA treatment (p>0.05).
|Adverse drug events (ADEs)||Twenty-two of 66 (33%) patients discontinued taking 9-CRA because of headache (11), dry skin (5), alopecia (4), or fatigue (3). One patient stopped after the diagnosis of a brain lesion, unrelated to test drug. Tolerated ADEs included headache (15), elevated triglycerides (7), and at lower frequency (<7%), desquamation/rash, neutropenia, pneumonia, fever, fatigue, edema, and elevated liver function tests.|
|Presenter conclusions||The test drug, 9-CRA, shows efficacy in AKS patients. Efficacy occurs in the absence of antiviral activity and confounding by antiviral agents. Future studies ought to use lower doses of 9-CRA because of the ADEs induced with once daily dosing at 60 to 100 mg/msq.|
Presented at the American Society of Clinical Oncology (ASCO) Meeting,
May 16-19, 1998
Copyright © 1998 Conrad Group Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / June 1998
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