Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma

Abstract

Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m(2)) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T(1)S(1)). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at (http://www.clinicaltrials.gov) as no. NCT00020449.

Figures

Figure 1

Photographs of the feet and computed tomographs of the chest of a patient treated with IL-12 and liposomal doxorubicin. Images in panels A and C were taken at baseline; those in panels B and D were taken at 22 months of treatment, the time of complete response. This patient was docu-mented to have a partial response at 4 weeks. Panels A and B were taken by NIH Patient Photographic Services using Nikon Digital SLR cameras (D1 and D1X respectively). Computed tomography scans were acquired from the NIH Clinical Center Diagnostic Radiology Department using the Kodak Carestream PACS web-based program. Images were imported into Adobe Photoshop v7 (Adobe Systems, San Jose, CA) for cropping and labelling. The images were then converted into a single Microsoft JPEG using MS Word 2003 (Microsoft, Seattle, WA) for importing into the manuscript as a single picture.

Figure 2

Progression-free survival of all patients. Time includes both time that they were being treated and a period of observation after treatment.

Figure 3

Serum interleukin-12 (IL-12), interferon-gamma (IFN-γ), and inducible protein-10 (IP-10) before and after the first dose of subcutaneous 300 ng/kg IL-12, a dose at week 18, and a dose at week 34. Patients 1 to 3 at week 18 and patients 7 and 8 at week 34 received 300 ng/kg IL-12; the others received 500 ng/kg.