Saturday, July 5, 2008

Doxorubicin Liposome Injection (Doxil) Approved for AIDS-Related Kaposi's Sarcoma

Doxorubicin Liposome Injection (Doxil) Approved for AIDS-Related Kaposi's Sarcoma

On June 10, the FDA approved a new indication for doxorubicin HCl liposome injection (Doxil; Alza Corp), allowing its use for the treatment of AIDS-related Kaposi's sarcoma after failure of previous systemic chemotherapy or intolerance to such therapy.

The recommended dose for patients with Kaposi's sarcoma is 20 mg/m2 (doxorubicin HCl equivalent), administered intravenously once every 3 weeks. Duration of treatment may vary according to efficacy and tolerance.

An initial infusion rate of 1 mg/minute is advised to minimize the risk for infusion-related reactions; if none are observed, the rate should be increased to complete administration of the drug for 1 hour. Dose delays and adjustments may be required for adverse events such as hand-foot syndrome, hematologic toxicities, and stomatitis.

The approval was based on data from an open-label, single-group, multicenter study of 77 patients with disease progression while receiving previous systemic combination therapy, 49 (64%) of whom had received doxorubicin HCl previously. Median time of the study was 155 days (range, 1 - 456 days), and the median cumulative dose was 154 mg/m2 (range, 20 - 620 mg/m2).

Therapeutic efficacy was evaluated in 2 analyses, the first being based on investigator assessment of changes in lesions over the entire body and the second on changes in up to 5 prospectively defined indicator lesions.

Results of the investigator assessment showed that 27% of patients achieved a partial response, defined as no new lesions, sites of disease, or worsening edema; flattening of 50% or more previously raised lesions or area of indicator lesions decreasing by 50% or more; and response lasting at least 21 days with no previous progression. The median time to response was 43 days (range, 15 - 133 days), and median duration of response was 73 days (range, 42 - 210 days).

A similar response rate (30%) was observed for patients who received doxorubicin previously, with a median time to response of 53 days (range, 15 - 109 days) and median duration of 89 days (range, 42 - 210 days).

Indicator lesion assessments revealed partial response rates of 48% for patients overall and 52% for those previously exposed to doxorubicin. The median time to lesion partial response for all patients was 22 days (range, 15 - 109 days), and its median duration was 71 days (range, 22 to ≥ 210 days). For those who had previously received doxorubicin, median time to response was 48 days (range, 15 - 109 days), and its duration was 79 days (range, 35 to ≥ 210 days).

After myelosuppression, the most commonly reported nonhematologic adverse events (incidence, ≥ 5%) reported in the study included nausea, asthenia, fever, alopecia, alkaline phosphatase increase, vomiting, diarrhea, stomatitis, and oral moniliasis.

Doxorubicin liposome injection was previously approved for the treatment of ovarian cancer after failure of platinum-based chemotherapy and in combination with bortezomib for the treatment of multiple myeloma in bortezomib-naive patients who have received at least 1 therapy previously.

Source: Medscape

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