PHASE-II STUDY OF PENTOSAN POLYSULFATE (PPS) IN PATIENTS WITH AIDS-RELATED KAPOSIS-SARCOMA

Aims and background: To evaluate the response rate, toxicity and survi val of patients with AIDS-related Kaposi's sarcoma (AIDS-KS) treated i n a phase II clinical trial of pentosan polysulpate (PPS), an inhibito r of basic-fibroblast growth factor Ib-FGF) which blocks the growth of Kaposi's sarcoma cells both in culture and in animal models. Patients and methods: Between March 1992 and March 1994 16 homosexual males wi th histopathologically confirmed AIDS-KS were accrued for this phase I I clinical trial. PPS was administered at the dose of 25 mg/m(2) q6 hr s at day 1, followed by 25 mg/m(2) q12 hrs daily by a subcutaneous inj ection. The number of patients to be included in the trial was calcula ted according to the two-stage Gehan method. Toxicity was graded accor ding to the NCI Common Toxicity Criteria, while responses were evaluat ed 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 ac etate (2 cases), Concomitant AZT (zidovudine) was given to 3 patients, while DDI (dideoxyinosine) was administered in one case. Results: A m edian of 5 (3-11) weeks of therapy was administered to the patients. P ain at the injection site and low grade fever were the only toxicities observed. Drug-related effects on coagulation parameters or thrombocy topenia were not observed in the trial, One objective response (6%) wa s documented, which lasted for 9 weeks, while stable disease was obser ved in three patients, lasting for 11, 9 and 5 weeks, respectively. Co nclusion: This is the first observation of objective antitumor activit y with a b-FGF inhibitor in patients with AIDS-KS. Considering its nov elty and the lack of significant toxicity, the authors suggest that th is experimental approach deserves further evaluation.