Paclitaxel Poliglumex and Estradiol in Treating Patients With Stage IV Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: transdermal estradiol; paclitaxel poliglumex
Intervention description: Transdermal estradiol given 0.2mg/day for duration of study.; Paclitaxel poliglumex (PPX) is a macromolecular polymer-drug conjugate of paclitaxel. PPX was given every 28 days, at a dose of 150 mg/m2
Intervention MeSH terms: Paclitaxel; Paclitaxel poliglumex; Estradiol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: Male
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as paclitaxel poliglumex, work in different ways
      to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Estradiol may kill prostate cancer cells that no longer respond to hormone therapy.
      Giving paclitaxel poliglumex together with estradiol may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving paclitaxel poliglumex together with
      estradiol works in treating patients with stage IV prostate cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed adenocarcinoma of the prostate

               -  Stage IV disease

                    -  Radiographic evidence of regional or distant metastases

          -  Evidence of disease progression (by PSA and/or imaging studies) despite standard
             hormonal therapy and after exposure to docetaxel-containing chemotherapy, as evidenced
             by any of the following:

               -  Measurable or evaluable disease progression, defined as the appearance of new
                  lesion(s) or unequivocal increase in previously existing lesions or masses

               -  Disease progression by PSA*, defined by 1 of the following:

                    -  3 consecutively rising PSA with the second PSA taken ≥ 1 week after the
                       first PSA

                    -  2 consecutively rising PSA with a fourth PSA > the second PSA NOTE: *The
                       last required PSA must be after the required antiandrogen washout period for
                       patients who have been on antiandrogen therapy

          -  Must have received prior therapy with at least two 3-weekly doses or six weekly doses
             of docetaxel

               -  Patients may have discontinued therapy due to progression, intolerance,
                  completion of planned therapy, or other reasons

               -  Prior treatment with combinations of docetaxel with estramustine phosphate sodium
                  or noncytotoxic agents (biologic agents) allowed

          -  Serum testosterone < 50 ng/dL (unless surgically castrate)

               -  Patients must continue androgen deprivation with a luteinizing hormone-releasing
                  hormone agonist if they have not undergone orchiectomy

          -  No known or suspected brain metastases

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  Life expectancy > 3 months

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Creatinine ≤ 1.5 times upper limit of normal (ULN)

          -  Bilirubin ≤ 1.5 times ULN

          -  AST and ALT ≤ 2.5 times ULN

          -  No other active malignancy except adequately treated nonmelanoma skin cancer or other
             noninvasive or in situ neoplasm

          -  No other significant active medical illness or infection that would preclude study
             compliance

          -  No significant cardiovascular illness, including any of the following:

               -  NYHA class III or IV congestive heart failure

               -  Unstable angina

               -  Myocardial infarction within the past 6 months

               -  Acute deep venous thrombosis

               -  Acute pulmonary embolism

          -  No significant peripheral neuropathy ≥ grade 2

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  At least 6 weeks since prior antiandrogen therapy (4 weeks for flutamide)

               -  No current evidence of an antiandrogen withdrawal response

          -  More than 4 weeks since prior radiotherapy

          -  More than 8 weeks since prior radiopharmaceutical therapy (strontium chloride Sr 89,
             samarium Sm 153 lexidronam pentasodium)

          -  No prior paclitaxel

          -  No other concurrent cytotoxic agents

          -  No other concurrent chemotherapy or biologic response modifiers

          -  No concurrent supplements known or suspected to contain supplemental estrogens