Effects of IAS in Men With Localized Biochemical Relapsed Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Flutamide; Leuprolide Acetate
Intervention description: Flutamide dosed at 250mg orally three times a day for 14 days prior to the initiation of Leuprolide Acetate.; Leuprolide Acetate dosed at 7.5mg intramuscular (IM) injections once per month for a total of 9 months.
Intervention MeSH terms: Leuprolide; Flutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: All subjects underwent androgen suppression with a two-week lead-in of Flutamide, followed by 9 monthly injections of Leuprolide Acetate. If PSA reached the appropriate nadir at by month 9, the androgen suppression was interrupted. Once the PSA reached the appropriate threshold, the subjects resumed treatment for another 9 months. These cycle continued until the patient withdrew from the study, was taken off the study due to toxicities or the decision of the investigator, or until the treatment with IAS was no longer effective in controlling the prostate cancer.
Masking: None (Open Label)
Enrollment: 102.0
Sex: Male
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Intermittent Hormone Therapy; Intermittent Androgen Suppression; Biochemical Relapsed Prostate Cancer; Androgen Deprivation Therapy; Localized Prostate Cancer

Summary:

      This study was a prospective analysis in men with localized prostate cancer who had rising
      Prostate Specific Antigen (PSA) levels after definitive treatment with surgery or radiation.
      Patients received Intermittent Androgen Suppression (IAS) in 9 month cycles until they became
      metastatic, became castrate resistant, or withdrew from the study. Subjects were monitored
      for time to development of Castration Resistant Prostate Cancer (CRPC) and overall survival.
      They were also monitored for the impact of IAS on a variety of neuro-psychiatric assessments
      and on bone density.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Biochemical relapse (rising PSA) after initial treatment (radiation therapy,
             brachytherapy, or radical prostatectomy) for histologically or cytologically confirmed
             adenocarcinoma of the prostate

          -  Clinical stage A2, B, C, D1

          -  Age: older than 21 years old

          -  Performance status of 0 or 1

          -  Pretreatment serum testosterone, normal range (or no clinical evidence of testosterone
             deficiency).

          -  If less than 30 months since completion of radiation therapy, biopsy of prostate
             suggested within 6 months of study entry. If more than or equal to 30 months since
             completion of radiation therapy, biopsy of prostate suggested within 1 year.

          -  Written informed consent.

        Exclusion Criteria:

          -  Abnormal bone scan suggestive of metastatic osseous disease.

          -  Previous hormonal manipulation including orchiectomy or any medication with
             significant antiandrogenic activity (combined androgen suppression over 9 months,
             monotherapy antiandrogens, estrogens, ketoconazole). *Neoadjuvant androgen suppression
             therapy of less than or equal to 3 months is allowed, if this androgen suppression
             therapy was completed more than or equal to 1 year prior to study enrollment AND if
             the Testosterone level is within the normal ranges.

          -  Any systemic chemotherapy or curative radiotherapy within 6 months.

          -  Hepatic dysfunction:

               -  Total bilirubin greater than 2.0 mg/dl

               -  Aspartate transaminase (AST; SGOT) greater than 3 times the upper limit of normal
                  range

               -  Lactate dehydrogenase (LDH) greater than 3 times the upper limit of normal
                  range).

          -  Renal dysfunction:

               -  Blood urea nitrogen (BUN) greater than 40 mg/dl

               -  Serum Creatinine greater than 2.0 mg/dl.

          -  History or presence of other malignancy within the last 5 years (except treated
             squamous/basal cell carcinoma of the skin or superficial bladder carcinoma).

          -  Hypersensitivity to flutamide or leuprolide.