Docetaxel, Estramustine, and Exisulind in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

OBJECTIVES:

• Determine the time to objective and biochemical progression and response proportion (objective and post-therapy changes in PSA) in patients with hormone refractory metastatic prostate cancer treated with docetaxel, estramustine, and exisulind.
• Determine the toxic effects of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: Patients receive oral estramustine 3 times daily on days 1-5, docetaxel IV over 1 hour on day 2, and oral exisulind twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

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