This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (15)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • HIV/AIDS  • Randomized Controlled Trial  • Immunologic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

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.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Oral Alitretinoin (9-cis-Retinoic Acid) Therapy for Chronic Hand Dermatitis in Patients Refractory to Standard Therapy: Results of a Randomized, Double-blind, Placebo-Controlled, Multicenter Trial
Ruzicka et al.
Arch Dermatol 2004;140:1453-1459.
ABSTRACT | FULL TEXT