Potential drug interaction with paclitaxel and highly active antiretroviral therapy in two patients with AIDS-associated Kaposi sarcoma.

Highly active antiretroviral therapy (HAART) consisting of multiple combinations of antiretroviral agents that inhibit HIV (HIV) replication has been associated with improvements in CD4+ T-lymphocyte cell counts, suppression of HIV replication, and regression of HIV-associated Kaposi's sarcoma (KS). Several of these agents have complex drug-drug interactions and have the potential to aggravate paclitaxel-associated toxicities. Herein two patients with KS are described who received paclitaxel while on HAART and who developed life-threatening toxicities. These cases are presented to alert clinicians to potentially serious drug interactions that can occur between various components of HAART and paclitaxel. Clinicians contemplating taxane-based chemotherapy for HIV-associated KS should carefully monitor patients for adverse events and, depending on their patient's HAART regimen, consider reducing the taxane dose.

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) 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 (>/=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/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/ micro L or lower were as likely to respond as patients with counts of higher than 150 cells/ micro L. 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.