9-cis-Retinoic Acid Capsules in the Treatment of AIDS-Related Kaposi Sarcoma

Abstract

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 per 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 (Ն50% 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 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 Ն62 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.

Oral Alitretinoin (9-cis-Retinoic Acid) Therapy for Chronic Hand Dermatitis in Patients Refractory to Standard Therapy

“…Much higher doses of oral alitretinoin have been given in previous studies to patients with solid tumors or as preventive anticancer therapy. For example, 34 patients received once-daily oral alitretinoin doses of 5 to 230 mg/m 2 for 4 weeks, 14 22 patients received twicedaily doses from 20 to 150 mg/m 2 per day for at least 4 weeks, 15 41 patients received once-daily (26 patients) or twice-daily (15 patients) doses up to 140 mg/m 2 for at least 4 weeks, 16 53 patients received once-daily doses from 60 to 100 mg/m 2 for a median of 15.1 weeks, 17 and 74 former smokers received once-daily doses up to 100 mg for 3 months. 18 Dose-limiting toxic effects reported at greater than 100 mg/m 2 per day were headache and diarrhea.…”

Role of Fat-Soluble Vitamins A and D in the Pathogenesis of Influenza: A New Perspective

“…Headache, a common symptom of in�uenza [117], is also a major feature of retinoid toxicity [118]. Conjunctivitis and photophobia are also common during acute seasonal in�uenza infection, especially in avian in�uenza A infections in humans [119].…”

Off-label uses of retinoids in dermatology

“…The median duration of treatment was 15.1 weeks. 9-cis-retinoic acid capsules have moderate activity and provide durable responses; however, substantial toxic effects at higher doses limit its suitability as an anti-KS therapy [118,119].…”