Rapid Hormonal Cycling as Treatment for Patients With Prostate Cancer: The Men's Cycle

• GnRH (Drug), also known as LUPRON, ZOLADEX: leuprolide and goserelin are gonadotropin-releasing hormone analogues
• Ketoconazole (Drug), also known as Nizoral: An imidazole antifungal agent. reduces adrenal and testicular androgen production in men
• Bicalutamide (Drug), also known as Casodex: A pure nonsteroidal antiandrogen
• Testosterone transdermal gel (Drug), also known as Androgel: an androgenic anabolic steroid
• Estrogen transdermal patch (Drug), also known as CLIMARA: Estradiol is the primary and most potent estrogen

Primary outcomes

• Response [6 months]: Complete Response: Normalization of the PSA (< or = to 4.0 for patients with castrate metastatic disease, or < 0.5 for patients with a rising PSA) that is maintained on 3 successive evaluations a minimum of 2 weeks apart. Partial Response: Decrease in PSA value by > or = to 50% from baseline value (without normalization) for 3 successive evaluations a minimum of 2 weeks apart. Stabilization: Patients who do not meet the criteria for PR or PROG for at least 90 days will be considered stable.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

-Patients residing in the following clinical states wit! be considered: A. Rising PSA: Patients with a history of localized disease who have undergone definitive radiation or surgery. These patients must demonstrate progression of disease biochemically as outlined below. Patients in this group may not have radiographically evident disease.

B. Non-castrate metastatic: Patients must present with radiographic evidence of metastatic disease at the time of diagnosis or after treatment for localized disease. These patients must show newly detected disease or progressing disease in bone or in soft tissue. Biochemical progression is defined as: minimum no. of determinations: 3 Interval: >2 weeks Minimal Baseline PSA value (ng/ml): 2 Minimal % increase in range of values: 50%

* Diagnosis of prostate adenocarcinoma histologically confirmed at MSKCC.
* Patient must have level of serum testosterone above the lower limit of normal.
* Karnofskcy performance status (KPS) >_70%.
* Patients must have adequate organ function as defined by the following laboratory criteria:
* WBC >_3500/mm3, platelet count >_100,000/mm3.
* Bilirubin <2.0 mg/dl or SGOT <3.0 X the upper limit of normal.
* Creatinine <_1.6 mg/dl or creatinine clearance >_60 cc/min.
* Prior hormonal therapy is allowed as:

  1. Neoadjuvant treatment prior to radiation therapy or radical prostatectomy, provided that the total duration of exposure does not exceed 10 months.
  2. One cycle of intermittent therapy up to a maximum exposure of 10 months.
* Patients must be at least 18 years of age.
* Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment

Exclusion Criteria:

* Clinically significant cardiac disease (New York Heart Association Class III/IV),or severe debilitating puhnonary disease.
* Uncontrolled serious active infection.
* Anticipated survival of less than 3 months.
* Active CNS or epiduraltumor
* Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests.

Participant flow

Outcome results

• Response (Primary), Number, participants: All Participants 22

Adverse events

Serious adverse events by term

Other adverse events by term

• Howard Scher, MD, Principal investigator, Memorial Sloan Kettering Cancer Center