RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of suramin is more effective for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of low, intermediate, and high dose suramin in treating men with stage IV prostate cancer that is refractory to hormone therapy.

OBJECTIVES:

• Compare the response in patients with advanced hormone-refractory adenocarcinoma of the prostate treated with low- vs intermediate- vs high-dose suramin.
• Compare the toxic effects of these regimens in these patients.
• Compare the overall and failure-free survival of patients treated with these regimens.
• Compare the duration of complete and partial responses in patients treated with these regimens.
• Determine the population pharmacokinetics of these regimens and correlate these parameters with the toxicity of these regimens and response rate in these patients.
• Compare the quality of life of patients treated with these regimens.
• Determine the relationship of absolute and relative decrease in PSA and rate of PSA decrease with the likelihood and duration of response in patients treated with these regimens.
• Determine whether a change in fibroblast growth factor levels in patients treated with suramin can be associated with the pharmacokinetics of suramin or the likelihood of clinical response in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease site (bone only vs soft tissue), CALGB/Zubrod performance status (0 or 1 vs 2), number of prior hormonal therapies (1 or 2 vs 3), and participating center. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive low-dose suramin IV over 1 hour on days 1, 2, 8, 9, 29, 30, 36, 37, 57, 58, 64, and 65 in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive intermediate-dose suramin as in arm I.
• Arm III: Patients receive high-dose suramin as in arm I. Patients with new progression after partial or complete response may receive additional courses, at the discretion of the study chairperson, beginning at least 12 weeks after completion of the first course and continuing in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed.

Patients are followed every 4 weeks until disease progression and then periodically for new primary cancer(s) and survival.

PROJECTED ACCRUAL: A total of 378 patients will be accrued for this study.

• Drug: chemotherapy
• Drug: suramin

• George DJ, Halabi S, Shepard TF, Sanford B, Vogelzang NJ, Small EJ, Kantoff PW. The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480. Clin Cancer Res. 2005 Mar 1;11(5):1815-20.
• Taplin ME, George DJ, Halabi S, Sanford B, Febbo PG, Hennessy KT, Mihos CG, Vogelzang NJ, Small EJ, Kantoff PW. Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study. Urology. 2005 Aug;66(2):386-91.
• Ahles TA, Herndon JE 2nd, Small EJ, Vogelzang NJ, Kornblith AB, Ratain MJ, Stadler W, Palchak D, Marshall ME, Wilding G, Petrylak D, Holland JC; Cancer and Leukemia Group B. Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480. Cancer. 2004 Nov 15;101(10):2202-8.
• Small EJ, Halabi S, Ratain MJ, Rosner G, Stadler W, Palchak D, Marshall E, Rago R, Hars V, Wilding G, Petrylak D, Vogelzang NJ. Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480. J Clin Oncol. 2002 Aug 15;20(16):3369-75.
• Bok RA, Halabi S, Fei DT, Rodriquez CR, Hayes DF, Vogelzang NJ, Kantoff P, Shuman MA, Small EJ. Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study. Cancer Res. 2001 Mar 15;61(6):2533-6.
• George DJ, Halabi S, Shepard TF, Vogelzang NJ, Hayes DF, Small EJ, Kantoff PW; Cancer and Leukemia Group B 9480. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res. 2001 Jul;7(7):1932-6.
• Halabi S, Vogelzang NJ, Kornblith AB, Ou SS, Kantoff PW, Dawson NA, Small EJ. Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol. 2008 May 20;26(15):2544-9.
• Halabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003 Apr 1;21(7):1232-7.

DISEASE CHARACTERISTICS:

• Histologically proven adenocarcinoma of the prostate with progressive metastatic or progressive regional nodal disease

  • PSA evidence of progression defined as at least 50% increase over baseline on at least 2 measurements at least 2 weeks apart

• Measurable disease preferred but not required

  • Bone scan abnormalities acceptable provided PSA at least 10 ng/mL
  • No minimum PSA value required if measurable disease present
• Progression after or during an adequate trial of hormonal therapy

• No more than 3 prior hormonal interventions for progressive disease

  • One prior hormonal intervention is defined by any of the following:

    • Concurrent testicular and adrenal androgen ablation (e.g., leuprolide, goserelin, orchiectomy, or diethylstilbestrol (DES) plus flutamide, bicalutamide, nilutamide, megestrol, or other antiandrogen)
    • Initial LHRH agonist followed by orchiectomy provided no progression prior to orchiectomy
    • Prior intermittent androgen deprivation on protocol SWOG-9346
    • Corticosteroids for metastatic disease or in conjunction with aminoglutethimide or ketoconazole

  • Two prior hormonal interventions are defined by the following:

    • Antiandrogen given for disease progression more than 3 months after initial hormonal therapy
• Prior neoadjuvant or adjuvant deprivation for treatment of nonmetastatic disease not considered a prior hormonal intervention

• Antiandrogen withdrawal not considered a separate hormonal intervention

  • At least 4 weeks since antiandrogen withdrawal or megestrol withdrawal
  • Failure to respond to (i.e., no decrease in PSA at 2 and 4 weeks) or progression after a transient response to antiandrogen withdrawal or megestrol withdrawal required
• Primary testicular androgen suppression (e.g., LHRH agonist or DES) continues during study
• No brain metastases or other CNS disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• CALGB 0-2 OR
• Zubrod 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,000/mm3
• Absolute neutrophil count at least 1,200/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 9 g/dL
• Fibrinogen at least 200 mg/dL
• No prior hemorrhagic or thrombotic disorders

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times normal
• Prothrombin time, partial thromboplastin time, and thrombin time normal

Renal:

• Creatinine clearance at least 70 mL/min

Other:

• No primary muscle disease
• No active, uncontrolled bacterial, viral, or fungal infection
• No grade 1 or worse peripheral neuropathy
• No underlying medical condition that would preclude study
• No other serious medical illness that limits survival to less than 3 months
• No psychiatric condition that would preclude informed consent
• No other malignancy within the past 5 years except inactive nonmelanomatous skin cancer or adequately treated stage I or II cancer in remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for metastatic disease

Chemotherapy:

• No prior chemotherapy (including estramustine) for metastatic disease

Endocrine therapy:

• See Disease Characteristics
• No concurrent megestrol or other hormonal agents
• No concurrent systemic or inhaled corticosteroids (intranasal and topical steroids allowed)

Radiotherapy:

• At least 4 weeks since prior radiotherapy (8 weeks for strontium therapy)

Surgery:

• See Disease Characteristics

Other:

• No prior experimental therapy for metastatic disease
• No concurrent heparin, warfarin, or aspirin

• National Cancer Institute (NCI)
• Southwest Oncology Group
• Eastern Cooperative Oncology Group