9-cis-retinoic acid capsules in the treatment of AIDS-related Kaposi sarcoma -: Results of a phase 2 multicenter clinical trial

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/m(2) pet day to a maximum of 140 mg/m(2) 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 (greater than or equal to50% 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/m(2). per day. Most patients found 140 mg/m(2) 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 I 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/muL or lower were as likely to respond as patients with counts of higher than 150 cells/muL. 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 greater than or equal to62 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.