Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Phase II study of the basic fibroblast growth factor (b-FGF)-inhibiting agent pentosan polysulfate (PPS) in patients with AIDS-related Kaposi's sarcoma (AIDS-KS) (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 14:A827 1995. Unique Identifier : AIDSLINE ICDB/95613979 Schwartsmann G; Mans DR; Machado VL; Sander E; Sprinz E; Kalakun L; South-American Office for Anticancer Drug Development, Porto; Alegre, RS, Brazil
Abstract:
The search for new anticancer agents which exhibit a high therapeutic index is critical, particularly in patients with AIDS-KS. In this context, inhibitors of angiogenesis are attractive candidates. As AIDS-KS is a highly vascularized tumor that overproduces the b-FGF variant K-FGF, we evaluated PPS for its efficacy in this disease. PPS is a semi-synthetic heparinoid which prevents the binding of b-FGF to its receptor on endothelial cells, and may thus inhibit tumor growth by cutting off its blood supply. This phase II study followed a two-stage Gehan method, and incorporated so far a total of 14 HIV-positive males with biopsy-proven progressing KS, median age between 18-75 years, WHO performance status 0-2, all of whom had given informed consent. PPS was administered sc at the schedule of 25 mg/m2 q 6 hr at day 1, followed by the same dose q 12 hr daily until disease progression. Responses were assessed after at least 2 treatment courses using the WHO criteria. One partial response (7%) was documented, with an 80% regression of tumor lesions, while 3 additional patients (21%) had stable disease for more than 40 days. The main side effects (using the CTC-NCI criteria) were fever grade 2 in 1 patient, local pain grade 2 in 2 patients and grade 1 PT/TTP changes. No bleeding was observed. In one patient, grade 4 thrombocytopenia occurred. As this side effect recovered spontaneously on therapy, it was considered disease-related by the investigator. Plasma samples for pharmacokinetic studies were collected in 5 patients, including the patient achieving a PR. A bioassay-based method is being developed for analysis. According to the Gehan method, one additional patient is still needed to complete the study. In summary, PPS showed objective antitumor activity in one patient with AIDS-KS at the above mentioned dose and schedule, which is rewarding for such a novel approach. As toxicity appears negligible, a new series of patients will be studied at a 50% higher dose-intensity in a new trial.
Keywords: Acquired Immunodeficiency Syndrome/*COMPLICATIONS Adolescence Adult Aged Antineoplastic Agents/PHARMACOKINETICS/*TOXICITY/*THERAPEUTIC USE Fibroblast Growth Factor, Basic/*ANTAGONISTS & INHIB Human Male Middle Age Pentosan Sulfuric Polyester/PHARMACOKINETICS/*TOXICITY/ *THERAPEUTIC USE Sarcoma, Kaposi's/*DRUG THERAPY/*ETIOLOGY/PATHOLOGY ABSTRACT CLINICAL TRIAL CLINICAL TRIAL, PHASE II 951230
M95C3210
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
