BACKGROUND: Treatment options are limited for patients with advanced acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (AIDS-KS) whose disease has progressed after receiving therapy with liposomal anthracyclines or combination chemotherapy with doxorubicin (Adriamycin), bleomycin, and vincristine (ABV). This study was performed to assess the safety and efficacy of a novel dose and schedule of paclitaxel in patients with AIDS-KS who failed to respond to previous systemic chemotherapy. METHODS: This was an open-label, multicenter Phase II study. Eligible patients had advanced AIDS-KS consisting of at least 25 mucocutaneous lesions, visceral disease, or lymphedema, and had failed to respond to at least one previous systemic chemotherapy regimen. Patients were treated with paclitaxel at a dose of 100 mg/m(2) given intravenously over 3 hours, every 2 weeks. Primary efficacy end points were tumor response, time to progression, time to treatment failure, and survival. Quality of life and adverse events were evaluated using the Symptom Distress Scale (SDS) and the World Health Organization Toxicity Criteria, respectively. RESULTS: One hundred and seven male patients with advanced AIDS-KS were enrolled from nine participating sites. The median entry CD4+ lymphocyte count was 41/mm(3) (range 0-1139). Previous treatment regimens included ABV in 52, liposomal daunorubicin in 49, and liposomal doxorubicin in 40 patients. Forty-one patients (38%) received two or more previous chemotherapy regimens. Protease inhibitor use during the study was reported by 82 (77%) patients overall; 47 patients (44%) were receiving a protease inhibitor before study entry. Complete or partial response was documented in 60 patients (56%). The median duration of response was 8.9 months. Major response rate was similar when comparing patients not on a protease inhibitor at the time of response (59%) with patients on a protease inhibitor at time of response (54%). However, protease inhibitor use had a significant impact on survival (P = 0.04). Grade 4 neutropenia was reported in 35% of patients; other life-threatening side effects were uncommon. Significant improvements were seen in the total quality of life scores measured by the SDS, including significant improvement in KS-related symptoms such as facial disease, tumor-associated edema, and pulmonary involvement. CONCLUSION: Paclitaxel given every 2 weeks induces major tumor regression in the majority of patients with advanced KS who failed to respond to previous systemic chemotherapy. Paclitaxel is associated with significant improvement in quality of life with acceptable toxicity and should be considered as an effective treatment option for patients with advanced KS.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Designing babies: genetic manipulation has just led to the birth of an Alzheimer's-free baby. Is this a step toward a 'Brave New World'? or a needed medical advance?

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Alzheimer Disease↗

PubMed2002

Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma.

OBJECTIVE: To assess the efficacy, safety and tolerance of oral 9-cis-retinoic acid in HIV-infected patients with Kaposi's sarcoma. METHODS: Sixty-six patients with AIDS-related Kaposi's sarcoma were enrolled at 14 centers; 60 received the study medication and were analyzed and, of these, 45 (75%) had received prior therapy for Kaposi's sarcoma. Once daily oral 9-cis-retinoic acid (alitretinoin, Panretin) was administered at doses up to 140 mg/m2. Most patients (72%) received a maximum dose of 100 mg/m2. Response was assessed using AIDS Clinical Trials Group (ACTG) criteria. RESULTS: The median age was 38 years and the median absolute CD4 cell count was 194 x 10(6) cells/l (range 6-784 x 10(6)). Despite the use of three- and four-drug antiviral regimens (83%), the median HIV RNA at baseline was 8701 copies/ml [range < 500 (lower limit of detection) to 4.24 x 10(6)]. The tumor response rate was 37% (95% confidence interval 25-49). Tumor response was associated with improved quality-of-life measures. There was a significant increase in interleukin 6 (IL-6) levels from baseline to week 4. Responders had significantly lower baseline soluble IL-6 receptor levels (P = 0.029) than non-responders. The median time to response was 9 weeks (mean, 13 weeks; range, 4-36). HIV RNA levels did not change significantly during therapy nor did they correlate with tumor responses. Study drug was discontinued by 28 patients for adverse events, which included headache (13) and skin toxicity (10). CONCLUSION: Oral 9-cis-retinoic acid is an active antitumor drug for AIDS-related Kaposi's sarcoma. Treatment is associated with skin and constitutional toxicity and further studies are needed to improve its long-term tolerance.

Administration, Oral↗

PubMed1999

The moral way to pay for human organs.

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Cadaver↗