Phase II study of pentosan polysulfate (PPS) in patients with AIDS-related Kaposi's sarcoma. 1996

G Schwartsmann, and E Sprinz, and L Kalakun, and N Yamagushi, and E Sander, and I Grivicich, and R Koya, and D R Mans
Department of Medical Oncology, Academic Hospital of Porto Alegre (HCPA), Federal University of Rio Grande do Sul, Brazil.

OBJECTIVE To evaluate the response rate, toxicity and survival of patients with AIDS-related Kaposi's sarcoma (AIDS-KS) treated in a phase II clinical trial of pentosan polysulpate (PPS), an inhibitor of basic-fibroblast growth factor (b-FGF) which blocks the growth of Kaposi's sarcoma cells both in culture and in animal models. METHODS Between March 1992 and March 1994 16 homosexual males with histopathologically confirmed AIDS-KS were accrued for this phase II clinical trial. PPS was administered at the dose of 25 mg/m2 q6 hrs at day 1, followed by 25 mg/m2 q12 hrs daily by a subcutaneous injection. The number of patients to be included in the trial was calculated according to the two-stage Gehan method. Toxicity was graded according to the NCl Common Toxicity Criteria, while responses were evaluated according to the WHO Criteria adapted for KS lesions. Patients were all homosexual males, median age 35 (27-43) years, performance status (WHO) 1 (0-2), NYU stage II-IV and prior therapy included vincristine and etoposide (3 cases), local irradiation (4 cases) and megestrol acetate (2 cases). Concomitant AZT (zidovudine) was given to 3 patients, while DDI (dideoxyinosine) was administered in one case. RESULTS A median of 5 (3-11) weeks of therapy was administered to the patients. Pain at the injection site and low grade fever were the only toxicities observed. Drug-related effects on coagulation parameters or thrombocytopenia were not observed in the trial. One objective response (6%) was documented, which lasted for 9 weeks, while stable disease was observed in three patients, lasting for 11, 9 and 5 weeks, respectively. CONCLUSIONS This is the first observation of objective antitumor activity with a b-FGF inhibitor in patients with AIDS-KS. Considering it novelty and the lack of significant toxicity, the authors suggest that this experimental approach deserves further evaluation.

UI MeSH Term Description Entries
D008297 Male Males
D010426 Pentosan Sulfuric Polyester A sulfated pentosyl polysaccharide with heparin-like properties. Pentosan Polysulfate,Polypentose Sulfate,BAY-946,Elmiron,Fibrocid,HOE-946,HOE-BAY 946,HOE-BAY-946,Hemoclar,PZ-68,PZ68,Pentosan Polysulfate Sodium,Pentosan Polysulphate Sodium,Pentosane Sulfuric Polyester,Polysulfated Xylan,SP-54,Tavan SP 54,Xylan SP54,Xylan Sulfate,BAY 946,HOE 946,HOE BAY 946,PZ 68,Polyester, Pentosan Sulfuric,Polyester, Pentosane Sulfuric,Polysulfate Sodium, Pentosan,Polysulfate, Pentosan,Polysulphate Sodium, Pentosan,SP 54,SP 54, Tavan,SP54,SP54, Xylan,Sodium, Pentosan Polysulfate,Sodium, Pentosan Polysulphate,Sulfate, Polypentose,Sulfate, Xylan,Sulfuric Polyester, Pentosan,Sulfuric Polyester, Pentosane,Xylan, Polysulfated
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012514 Sarcoma, Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Kaposi's sarcoma occurs spontaneously in Jewish and Italian males in Europe and the United States. An aggressive variant in young children is endemic in some areas of Africa. A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, pp2105-7) HHV-8 is the suspected cause. Kaposi Sarcoma,Kaposi's Sarcoma,Multiple Idiopathic Pigmented Hemangiosarcoma,Kaposis Sarcoma,Sarcoma, Kaposi's
D016019 Survival Analysis A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. Analysis, Survival,Analyses, Survival,Survival Analyses
D016222 Fibroblast Growth Factor 2 A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1). Basic Fibroblast Growth Factor,Fibroblast Growth Factor, Basic,HBGF-2,Cartilage-Derived Growth Factor,Class II Heparin-Binding Growth Factor,FGF-2,FGF2,Fibroblast Growth Factor-2,Heparin-Binding Growth Factor Class II,Prostate Epithelial Cell Growth Factor,Prostatropin,Cartilage Derived Growth Factor,FGF 2

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