UK studies on suramin therapy in hormone resistant prostate cancer.
New insights regarding the biology of hormone resistant CaP have shown that major growth factors other than testosterone are responsible for cellular proliferation of androgen resistant prostate cancer cells. In vitro studies have confirmed the efficacy of growth factor inhibitors such as suramin in reducing cellular proliferation of androgen dependent LNCaP and independent PC-3 CaP cell lines as well as CaP cells obtained by primary culture. Initial clinical trials using high dose suramin (peak serum concentration 250-300 micrograms/ml) as monotherapy in patients with hormone resistant CaP have shown some promise, but the duration of response to therapy has been short lived and suramin toxicity is a problem. To minimize toxicity without reducing anti-tumour activity, studies evaluating its use in combination with other cytotoxic drugs are attractive in CaP. Suramin and doxorubicin, tumour necrosis factor and EMP have shown synergy in vitro. However, in a phase II clinical trial using combination therapy with low dose suramin (140 micrograms/ml) and mitomycin C in 32 patients, there was one complete response and six partial responses, and in 15 patients, the disease had stabilized. The median time to treatment failure was 103 days, and the median survival was 209 days. This regimen caused significant toxicities. The present study has shown that the combination of EMP 280 mg twice a day and suramin 1 g weekly infusions for 6 weeks, compared to EMP 280 mg alone, showed a statistically significant difference in the rate of depression of PSA levels after 3 and 6 months of treatment (p < 0.01) and a statistically significant reduction in bone pain and requirement for analgesics in patients on combination therapy-100% compared to 0% for patients on EMP alone.
Kehinde
E O
EO
Department of Urology, University of Leicester, Leicester General Hospital.
Terry
T R
TR
Mistry
N
N
Horsburgh
T
T
Sandhu
D P
DP
Bell
P R
PR
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004351:Drug Resistance; D005485:Flutamide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013498:Suramin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D013498:Suramin; D005485:Flutamide