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Suramin: a novel growth factor antagonist with activity in hormone-refractory metastatic prostate cancer
1Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Purpose:
Suramin is known to inhibit the growth of malignant prostate carcinoma cells in vitro. This led us to evaluate the effectiveness of suramin in the treatment of 38 patients with prostate carcinoma refractory to hormone therapy.
Patients And Methods:
Suramin was administered by continuous infusion at a rate designed to reach a peak of 300 micrograms/mL at the end of 14 days. Patients were given 8 weeks to recover from any toxicity before beginning the second cycle. Subsequent cycles were administered in the same manner except the starting dose rate was 280 mg/m2.
Results:
In 17 patients with measurable soft tissue disease, three had complete disappearance of soft tissue disease for 4, 5, and 11 months, whereas three patients had a greater than or equal to 50% decrease in the sum of the products of the diameters of all measurable disease for greater than or equal to 1 month. Of these 17 patients, pretreatment prostate-specific antigen (PSA) decreased by 75% or more in five (29%) and normalized in one (6%). The remaining 21 patients had disease limited to bone, and only one of these experienced resolution of more than 50% of all lesions on bone scan. Of these 21 patients, pretreatment PSA decreased by 75% or more in eight (38%) and normalized in five (25%). Median time to progression for all patients was 26.3 weeks, and median survival was 42.3 weeks. Patients with bone involvement alone exhibited a better survival than patients with soft tissue involvement (P2 = .02). Survival was strongly correlated (P2 = .0001) with a decline in the pretreatment PSA of greater than or equal to 75% by the eighth week on therapy, with nearly an 85% survival at 1 year compared with a 20% survival for those whose pretreatment PSA did not decline by that amount.
Conclusion:
We conclude that suramin is an active agent in hormone-refractory prostate carcinoma.
Insights
Suramin shows activity in treating hormone-refractory prostate cancer. A significant number of patients experienced decreased prostate-specific antigen (PSA) levels and improved survival rates, particularly those with bone-only disease.
Area of Science:
- Oncology
- Pharmacology
Background:
- Malignant prostate carcinoma cell growth is inhibited by suramin in vitro.
- Hormone therapy is a standard treatment for prostate cancer, but resistance can develop.
Purpose of the Study:
- To evaluate the effectiveness of suramin in patients with prostate carcinoma refractory to hormone therapy.
Main Methods:
- Thirty-eight patients with hormone-refractory prostate carcinoma received suramin via continuous infusion.
- Treatment involved cycles with dose adjustments and recovery periods for toxicity.
Main Results:
- In patients with soft tissue disease, three achieved complete disappearance, and three had >=50% decrease in measurable disease.
- Significant PSA declines were observed in both soft tissue and bone-limited disease groups.
- Median time to progression was 26.3 weeks, and median survival was 42.3 weeks.
- Bone-only involvement correlated with better survival; PSA decline strongly predicted survival.
Conclusions:
- Suramin is an active agent in treating hormone-refractory prostate carcinoma.
- The drug demonstrates efficacy in reducing tumor burden and improving survival outcomes.