© 1993 by Oxford University Press
Journal of the National Cancer Institute, Vol. 85, No. 19, 1585-1592,
October 6, 1993
© 1993 Oxford University Press
Administration of Pentosan Polysulfate to Patients With Human Immunodeficiency Virus-Associated Kaposi's Sarcoma
Medicine Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health Bethesda, Md
Dermatology Branch, Intramural Research Program, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute, National Institutes of Health Bethesda, Md
Clinical Pharmacology Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health Bethesda, Md
Office of the Director, National Cancer Institute, National Institutes of Health Bethesda, Md
Clinical Pathology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health Bethesda, Md
Department of Pharmacy, Warren Grant Magnuson Clinical Center, National Institutes of Health Bethesda, Md
to: James M. Pluda, M.D., National Cancer Institute, 6130 Executive Blvd., Executive Plaza North, Rm. 715, Rockville, MD 20852.
Background: Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. Purpose: The purpose of this phase I clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. Methods: Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3–6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. Results: The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3–27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. Conclusion: Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. Implication: Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted. [J Natl Cancer Inst 85: 1585–1592, 1993]
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