A Phase II Study Of Estramustine, Docetaxel, And Exisulind (IND #64733) In Men With Hormone Refractory Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- Progressive systemic (metastatic) disease despite castrate levels of
testosterone secondary to orchiectomy or luteinizing hormone-releasing hormone
(LHRH) agonist therapy

- Castrate levels of testosterone must be maintained

- LHRH analog therapy should be continued

- Failed prior standard androgen-deprivation therapy

- Serum testosterone no greater than 50 ng/mL for patients who have not had
bilateral orchiectomy

- Evidence of metastatic disease on CT scan, MRI, or bone scan (no positron-emission
tomography or prostascint)

- Evidence of progressive disease after most recent prior therapy (including hormonal
therapy) as defined by 1 of the following:

- Measurable disease progression

- More than 20% increase in the sum of the longest diameters of target
lesions from the time of maximal regression or the appearance of 1 or more
new lesions

- Bone scan progression

- Appearance of 1 or more new lesions on bone scan attributable to prostate
cancer AND

- PSA at least 5 ng/mL

- PSA progression

- PSA at least 5 ng/mL which has increased serially from baseline on 2
occasions (at least 1 week apart) NOTE: If the confirmatory PSA is less
than screening PSA, an additional test for rising PSA is required

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic

- AST and ALT no greater than 1.5 times upper limit of normal (ULN)

- Bilirubin no greater than ULN

Renal

- Creatinine no greater than 1.5 times ULN

Cardiovascular

- No myocardial infarction within the past year

- No significant change in anginal pattern within the past year

- No congestive heart failure

- No New York Heart Association class II-IV heart disease

- No deep vein thrombosis within the past year

Pulmonary

- No pulmonary embolus within the past year

Other

- No clinically significant peripheral neuropathy

- No known hypersensitivity to sulindac

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior cytotoxic chemotherapy (including estramustine or suramin)

- No other concurrent chemotherapy

Endocrine therapy

- See Disease Characteristics

- At least 4 weeks since prior flutamide and megestrol

- At least 6 weeks since prior bicalutamide and nilutamide

- At least 4 weeks since prior hormonal therapy known to decrease PSA levels (including
ketoconazole, aminoglutethimide, finasteride, or any systemic corticosteroid)

- Concurrent primary testicular androgen suppression therapy (e.g., with a LHRH analog)
allowed

- No other concurrent hormonal therapy except:

- Steroids for adrenal insufficiency

- Hormones for non-disease-related conditions (e.g., insulin for diabetes)

- Intermittent dexamethasone as an antiemetic

Radiotherapy

- At least 4 weeks since prior radiotherapy and recovered

- At least 8 weeks since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam
pentasodium

- No concurrent palliative radiotherapy

Surgery

- See Disease Characteristics

- At least 4 weeks since prior major surgery and recovered

Other

- At least 4 weeks since prior herbal product known to decrease PSA levels (including
saw palmetto, PC-SPES)

- More than 1 week since prior sulindac

- No concurrent sulindac

- No concurrent chronic nonsteroidal anti-inflammatory drugs (including COX-2
inhibitors and salicylates such as aspirin, mesalamine, salsalate, and sulfasalazine)

- Concurrent ibuprofen and naproxen allowed

- Low-dose aspirin (e.g., 81 mg/day) for cardiovascular prevention allowed

- No concurrent full-dose oral or parenteral anticoagulation therapy

- Concurrent bisphosphonate therapy allowed provided therapy was initiated at least 4
weeks before study and disease has progressed despite therapy