The experience with suramin in advanced prostate cancer

Abstract

Suramin is a new experimental polyanionic compound that has shown evidence of antitumor activity in patients with hormone refractory prostate cancer. After a few years of Phase I and Phase II testing, much of the drug's toxicity pattern has been carefully characterized. Similarly, pharmacologic studies have defined many of the drug's complex pharmacologic properties to the extent that simple outpatient methods of drug administration can be easily accomplished. A pharmacologically derived, fixed outpatient schedule has been shown to be safe and effective and is currently in active Phase III development in prostate cancer and will provide more definitive data regarding the role of suramin in the treatment of this disease. Despite these accomplishments, a number of questions require further study, such as definition of pharmacodynamic correlations, effects on the hypothalamic‐pituitary‐adrenal and gonadal axis, and the nature of its most common dose‐limiting toxicity, which is a syndrome of malaise and fatigue. Cancer 1995;75:1927–34.

Probing the Interaction of Dengue Virus Envelope Protein with Heparin: Assessment of Glycosaminoglycan-Derived Inhibitors

“…These HA oligosaccharides were fractionated on the basis of size to obtain a series of oligosaccharides ranging from decasaccharide to ecosisaccharide, and were demonstrated to be pure by HPLC, capillary electrophoresis, and 1 H NMR . Each HA oligosaccharide was persulfated using the same method used for the intact GAGs, and the products were analyzed by capillary electrophoresis and gradient PAGE for purity, following hydrolysis for sulfate content and by 1 H NMR. , While the persulfated HA oligosaccharides bound significantly more weakly than did the intact persulfated HA, the larger persulfated HA oligosaccharides bound nearly as tightly as heparin, assessed by both competitive and direct binding assays. The strength of this interaction increased with oligosaccharide size from dp 10 through dp 20.…”

“…The polyanions examined in this study include several that are currently used as drugs and excipients. Small synthetic polyanions (Figure 1) including Suramin (an antineoplastic and antihelminthic agent), 15 sucrose octasulfate (the active component in Sucralfate), 16 sulfated lactobionic acid (an antithrombotic in clinical evaluation), 17 and sulfated β-cyclodextrin (an excipient) 18 were evaluated. We also evaluated the natural polyanionic polysaccharides known as glycosaminoglycans (GAGs): heparin (an anticoagulant/antithrombotic), heparan sulfate, chondroitin sulfate, and dermatan sulfate (all components of the antithrombotic ORG10172) 19 and hyaluronic acid (an ophthalmic and antiarthritic agent).…”

The management of prostate cancer in patients with a rising prostate‐specific antigen level

“…Clinical disease progression of hormone‐refractory prostate cancer manifests predominantly as metastases to the bones and less frequently as soft‐tissue nodal, lung or liver disease. Of 109 patients with hormone‐refractory prostate cancer studied by Eisenberger et al [48], bone metastases were present in 108, soft‐tissue nodal disease in 15, lung metastases in six and metastases to the liver in four. However, in patients with bone metastases the response to treatment is difficult to assess; measurable lesions are often absent and bone scans are frequently inconclusive because bone repair processes and inflammatory reactions may appear as progressive disease on the scintigram.…”

The effects of Suramin on Ca2+activated force and sarcoplasmic reticulum Ca2+release in skinned fast-twitch skeletal muscle fibers of the rat

“…Due to global administration protocols and the broad acting nature of Suramin, a number of contraindications have been reported. Among the most significant side effects are severe fatigue, malaise and lethargy, which all may be manifest as a broad spectrum neuromuscular peripheral weakness of the hands, arms, legs and feet of patients (Eisenberger et al 1995;Grossman et al 2001). The skeletal muscle itself represents a large volume target for Suramin action, with the relative skeletal muscle mass of the body making up 30.6% AE5.5 of women and 38.4% AE5.1 in men (Janssen et al 2000).…”