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UK studies on suramin therapy in hormone resistant prostate cancer
E O Kehinde1, T R Terry, N Mistry
1Department of Urology, University of Leicester, Leicester General Hospital.
Abstract:
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.
Insights
New research indicates that combining etoposide (EMP) and suramin effectively treats hormone-resistant prostate cancer (CaP). This combination significantly reduces prostate-specific antigen (PSA) levels and alleviates bone pain, offering a promising therapeutic strategy for advanced CaP.
Area of Science:
- Oncology
- Pharmacology
Background:
- Hormone-resistant prostate cancer (CaP) proliferation is driven by growth factors beyond testosterone.
- Suramin shows in vitro efficacy against CaP cell lines but has limitations in clinical use due to toxicity and short response duration.
- Combination therapies are being explored to enhance anti-tumor activity and minimize toxicity in CaP treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of combining etoposide (EMP) with suramin for hormone-resistant prostate cancer.
- To compare the combination therapy against EMP monotherapy in terms of PSA level reduction and symptom management.
Main Methods:
- A study compared combination therapy (EMP 280 mg twice daily + suramin 1 g weekly infusions for 6 weeks) against EMP monotherapy in patients with hormone-resistant CaP.
- Outcomes measured included prostate-specific antigen (PSA) level changes at 3 and 6 months, bone pain, and analgesic requirements.
Main Results:
- The combination therapy demonstrated a statistically significant difference in the rate of PSA level depression at 3 and 6 months (p < 0.01) compared to EMP alone.
- Patients receiving the combination therapy experienced a 100% reduction in bone pain and analgesic requirements, versus 0% for EMP monotherapy.
- The study highlights the synergistic potential of EMP and suramin in managing hormone-resistant prostate cancer.
Conclusions:
- Combination therapy with etoposide and suramin is a promising strategy for hormone-resistant prostate cancer.
- This regimen significantly improves key clinical markers, including PSA levels and patient-reported pain.
- Further investigation into this combination therapy could lead to improved treatment outcomes for advanced prostate cancer.