Suramin's development: what did we learn?
Suramin, a polysulphonated napthylurea, has been extensively evaluated over the past 10 years as an anticancer agent, with the most interest in the treatment of prostate cancer. Early clinical results were promising with response rates of up to 70% being reported. However, a recent double-blind study showed only modest palliative effect in patients with androgen independent prostate cancer. In retrospect, it appears those initial reports failed to control for confounding variables such as antiandrogen withdrawal and hydrocortisone. Suramin causes numerous reversible toxicities (lethargy, rash, fatigue, anemia, hyperglycemia, hypocalcemia, coagulopathies, neutropenia, renal and hepatic complications). Neurotoxicity has been the most significant complication and appears to be related to the intensity of the dosing regimen. An optimal therapeutic dose has not been determined, but it is clear that adaptive controls add little benefit. Aside from moderate toxicities and the low therapeutic index in patients with prostate cancer, suramin's development has taught us some valuable lessons (i.e., anti-androgen withdrawal was noted during suramin's development, the use of PSA as an indicator of tumor burden was initiated during the evaluation of suramin). These lessons can be applied to all clinical trials in hormone refractory prostate cancer. Suramin has significantly enhanced the evolution of our knowledge in several areas of prostate cancer biology and treatment.
Kaur
Maninderjeet
M
Molecular Pharmacology Section, Cancer Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
Reed
Eddie
E
Sartor
Oliver
O
Dahut
William
W
Figg
William D
WD
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013498:Suramin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016019:Survival Analysis; D014018:Tissue Distribution; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013498:Suramin; D017430:Prostate-Specific Antigen