Data from 2, Phase 2 open-label studies support the use of paclitaxel as second-line therapy in patients with AIDS-related Kaposi's sarcoma. Fifty-nine of the 85 patients enrolled in these studies had previously received systemic therapy, including interferon alpha (32%), DaunoXome® (31%), DOXIL® (2%), and doxorubicin containing chemotherapy (42%), with 64% having received prior anthracyclines. Eighty-five percent of the pretreated patients had progressed on, or could not tolerate, prior systemic therapy.1

In Study CA139-174, patients received paclitaxel at 135 mg/m2 as a 3-hour infusion every 3 weeks (intended dose intensity 45 mg/m2/week). If no dose-limiting toxicity was observed, patients were to receive 155 mg/m2 and 175 mg/m2 in subsequent courses. Hematopoietic growth factors were not to be used initially. In Study CA139-281, patients received paclitaxel at 100 mg/m2 as a 3-hour infusion every 2 weeks (intended dose intensity 50 mg/m2/week). In this study patients could be receiving hematopoietic growth factors before the start of paclitaxel therapy, or this support was to be initiated as indicated; the dose of paclitaxel was not increased. The dose intensity of paclitaxel used in this patient population was lower than the dose intensity recommended for other solid tumors. 

All patients had widespread and poor-risk disease. Applying the ACTG staging criteria to patients with prior systemic therapy, 93% were poor risk for extent of disease (T1), 88% had a CD4 count <200 cells/mm3 (I1), and 97% had poor risk considering their systemic illness (S1). 

All patients in Study CA139-174 had a Karnofsky performance status of 80 or 90 at baseline; in Study CA139-281, there were 26 (46%) patients with a Karnofsky performance status of 70 or worse at baseline. 

Although the planned dose intensity in the 2 studies was slightly different (45 mg/m2/week in Study CA139-174 and 50 mg/m2/week in Study CA139-281), delivered dose intensity was 38 to 39 mg/m2/week in both studies, with a similar range (20 to 24 to 51 to 61). 

Efficacy: The efficacy of paclitaxel was evaluated by assessing cutaneous tumor response according to the amended ACTG criteria and by seeking evidence of clinical benefit in patients in 6 domains of symptoms and/or conditions that are commonly related to AIDS-related Kaposi's sarcoma. 

Cutaneous Tumor Response (Amended ACTG Criteria): The objective response rate was 59% (95% CI, 46% to 72%) (35 of 59 patients) in patients with prior systemic therapy. Cutaneous responses were primarily defined as flattening of more than 50% of previously raised lesions. 

The median time to response was 8.1 weeks and the median duration of response measured from the first day of treatment was 10.4 months (95% CI, 7.0 to 11.0 months) for the patients who had previously received systemic therapy. The median time to progression was 6.2 months (95% CI, 4.6 to 8.7 months). 

Additional Clinical Benefit: Most data on patient benefit were assessed retrospectively (plans for such analyses were not included in the study protocols). Nonetheless, clinical descriptions and photographs indicated clear benefit in some patients, including instances of improved pulmonary function in patients with pulmonary involvement, improved ambulation, resolution of ulcers, and decreased analgesic requirements in patients with Kaposi's sarcoma (KS) involving the feet and resolution of facial lesions and edema in patients with KS involving the face, extremities, and genitalia. 

Safety: The adverse event profile of paclitaxel administered to patients with advanced HIV disease and poor-risk AIDS-related Kaposi's sarcoma was generally similar to that seen in the pooled analysis of data from 812 patients with solid tumors. These adverse events and adverse events from the Phase 2 second-line Kaposi's sarcoma studies are described in the ADVERSE REACTIONS section in tabular (Tables 10 and 16) and narrative form. In this immunosuppressed patient population, however, a lower dose intensity of paclitaxel and supportive therapy including hematopoietic growth factors in patients with severe neutropenia are recommended. Patients with AIDS-related Kaposi's sarcoma may have more severe hematologic toxicities than patients with solid tumors.