Elsevier

Urology

Volume 53, Issue 3, March 1999, Pages 535-541
Urology

Adult Urology
Suramin treatment in hormone- and chemotherapy-refractory prostate cancer

https://doi.org/10.1016/S0090-4295(98)00544-5Get rights and content

Abstract

Objectives. Suramin, a polysulfonated naphtylurea with anti-growth factor activity, was used in the treatment of metastatic, hormone- and chemotherapy-refractory prostate cancer. Recent studies have proved the effect of suramin on prostate cancer.

Methods. Between March 1990 and January 1994, 27 patients with metastatic prostate cancer were enrolled in this study. Treatment regimen consisted of a loading phase, allowing patients to reach suramin serum levels between 180 and 250 μg/mL using a suramin dose of 1.4 g/m2 at 3-day intervals. Constant suramin serum levels were maintained by a 0.5 to 1-g/m2 dose every 7 to 10 days. Because previous studies showed suramin to have serious toxicity, compromised organ status was excluded by repeated examinations.

Results. Six patients did not complete the suramin loading phase because of side effects and were removed from the study. With an average cumulative suramin dose of 14.2 g, 33% of the assessable patients (7 of 21) experienced a more than 50% reduction of prostate-specific antigen (PSA) and/or alkaline phosphatase (AP) serum levels. Mean survival in these suramin-responsive patients was 495 days. Two of these patients experienced a remarkable reduction of metastases in bone scan examinations. Another 48% of the patients (10 of 21) had essentially unchanged AP and PSA serum levels during suramin treatment, indicating stable disease. Mean survival of these patients was 341 days. In 4 patients undergoing suramin treatment, continuous clinical progression of the disease was observed (mean survival 79 days). Toxicity was less or comparable to prior reported studies; the most common side effects were polyneuropathy, allergic skin rash, and vortex keratopathy.

Conclusions. Suramin has limited, but significant, efficacy even in chemotherapy- and hormone-refractory prostate cancer, without serious toxicity.

Section snippets

Patient characteristics and evaluation

Between March 1990 and January 1994, 27 patients with hormone- and chemotherapy-refractory metastatic cancer of the prostate were enrolled in this study after giving written informed consent. The study protocol was approved by the local ethics committee. Mean age was 60.8 years (range 50 to 78). The initial treatment at the time of diagnosis had been radical prostatectomy in 10 patients, external beam radiation therapy in 1 patient, and primary androgen ablation in 16 patients. Of the 10

Dosage

The average duration of suramin treatment was 108 days (range 3 to 461). In this time, patients were given between 3.0 and 49.3 g of suramin (average dose 14.7). In 6 patients, therapy was discontinued during the loading phase without reaching therapeutic levels because of side effects (see toxicity section). The 21 patients reaching therapeutic serum levels were treated with doses between 10.25 and 22.25 g of suramin during a single course, with a suramin infusion every 7 to 10 days. One

Comment

Epidemiologic studies indicate an increasing incidence of prostate cancer, especially in younger men. Curative therapy is limited to patients with organ-confined disease only. Once cancer is advanced or metastatic, only palliative treatment is available. Since Huggins and Hodges11 published their experience on the beneficiary effects of castration in these patients, androgen deprivation by operative or chemical means still represents the therapy of choice.

Despite modifications in hormonal

Acknowledgements

To Prof. Dr. Siekmann at the laboratories of clinical biochemistry at the University of Bonn for performing the high-performance liquid chromatography analysis of suramin serum levels and to Mr. Herde, who collected the data of our first set of patients.

References (26)

  • P.J. Rosen et al.

    Suramin in hormone-refractory metastatic prostate cancera drug with limited efficacy

    J Clin Oncol

    (1996)
  • R. Klecker et al.

    Quantification of suramin by reverse-phase ion-pairing high-performance liquid chromatography

    J Liq Chromatogr

    (1985)
  • Wittes RE: Manual of Oncologic Therapeutics, ed 1989–90. Philadelphia, JB Lippincott, 1989, pp...
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    Bruno Allolio was supported by Deutsche Forschungsgemeinschaft DFG (Al203/1–5).

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