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Results of a Phase 2 Multicenter Clinical Trial

David M. Aboulafia, MD; Dorece Norris, MD; David Henry, MD; Ronald J. Grossman, MD; James Thommes, MD; Denise Bundow, ARNP; Richard C. Yocum, MD; Victor Stevens, PhD

Arch Dermatol. 2003;139:178-186.

Objective  To evaluate the safety, dose tolerance, and anti-tumor effects of 9-cis-retinoic acid in the treatment of Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS).

Design  Phase 2, open-label clinical trial of oral doses of 9-cis-retinoic acid increasing in 40-mg increments every 2 weeks from 60 mg/m² per day to a maximum of 140 mg/m² per day.

Setting  Five hospital or health maintenance organization outpatient clinics.

Patients  Fifty-seven adult male patients with human immunodeficiency virus and biopsy-proven KS.

Main Outcomes Measures  Safety was evaluated by adverse events, physical examination, laboratory test abnormalities, treatment-limiting toxic effects, and reasons for early withdrawal. Response (50% improvement) was evaluated by an overall KS response and by the area and height from 6 index lesions selected at baseline.

Results  Patients tolerated 60 and 100 mg/m² per day. Most patients found 140 mg/m² per day intolerable owing to headache. Common treatment-related adverse events were headache, xerosis, rash, alopecia, and hyperlipemia. The patient response rate for the overall KS disease was 19% (11/57), including 1 patient with clinically complete response. The response rate assessed by measuring 6 index lesions during treatment was 39% (22/57). Sixteen responding patients (73%) were refractory to at least 1 previous anti-KS therapy. Patients with CD4⁺ counts of 150 cells/µL or lower were as likely to respond as patients with counts of higher than 150 cells/µL. The median time to response was 8.5 weeks (range, 4.0-21.1 weeks). The median duration of treatment was 15.1 weeks (range, 0.14 to 62 weeks).

Conclusion  9-cis-retinoic acid capsules have moderate activity and provide durable responses, but substantial toxic effects at higher doses limit its suitability as an anti-KS therapy.

From the Virginia Mason Medical Center, Seattle, Wash (Dr Aboulafia and Ms Bundow); Center for Quality Care, Tampa, Fla (Dr Norris); Graduate Hospital, Bala Cynwyd, Pa (Dr Henry); Anderson Clinical Research, Pittsburgh, Pa (Dr Grossman); Pacific Oaks Research, Beverly Hills, Calif (Drs Thommes and Yocum), and Ligand Pharmaceuticals Inc, San Diego, Calif (Dr Stevens). Drs Yocum and Stevens are employees of Ligand.

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