Docetaxel and Erlotinib in Treating Older Patients With Prostate Cancer

OBJECTIVES:

Primary

• Determine the response rate and response duration in older patients with progressive hormone refractory prostate cancer treated with docetaxel and erlotinib.

Secondary

• Determine the safety of this regimen in these patients.
• Evaluate the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Initial combination therapy: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib once daily on days 1-21. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease receive 3 additional courses beyond maximal response.
• Extension phase: After 9 courses of initial combination therapy, patients achieving a complete response, partial response, or stable disease receive 8 courses of erlotinib alone (total of 17 courses of study treatment).

Quality of life is assessed at baseline, day 1 of each course, and at the end of study treatment. For patients in the extension phase, quality of life is also assessed on day 1 of courses 10, 12, 14, and 16.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study within 24 months.

Inclusion criteria

• Histologically confirmed adenocarcinoma of the prostate.
• Disease progression following primary or secondary hormonal therapy.
• All patients must be maintained on GnRH analog during this study.
• Serum PSA must be > 20 ng/mL in patients without bidimensionally measurable disease or bone disease.
• Age > 65 years.
• Karnofsky performance status of > 70%.
• Life Expectancy of > 12 weeks.
• Peripheral neuropathy, if present must be < grade 1 by NCI criteria.
• Radionuclide bone scan and chest /abdominal/pelvic CT scan must be obtained in all patients within 4 weeks prior to cycle 1/day 1.
• Sexually active men must be willing to consent to using effective contraception while on treatment and for 6 months following treatment.
• No concomitant use of prostata or saw palmetto.
• Testosterone must be castrate levels(< 50 ng/ml).
• WBC > 2.8 x 109/L
• Granulocytes > 1.5 x 109/L
• Platelets > 100 x 109/L
• Hemoglobin > 8.0 g/dL
• Serum creatinine < 2.1
• Total bilirubin < ULN
• Alkaline Phosphatase < 2.5 ULN AND ALT/AST < 2.0 ULN OR Alkaline Phosphatase 2.6-3.9 ULN, AND ALT/AST <1.5 ULN OR Patients with known bone involvement may be included with alkaline phosphatase > 4.0 ULN, IF ALT and AST and total bilirubin are within the normal range and the bone involvement is thought to account for elevated alkaline phosphatase.
• PT, INR should be within physiologic limits, i.e. INR 0.7 - 1.5. If patient is receiving anticoagulation therapy then INR should be within the range of 2.0 - 3.5.

Exclusion criteria

• Any major surgery or radiotherapy, within 4 weeks prior to cycle 1/day 1 (within 12 weeks for previous treatment with strontium-89, rhenium, or sumarium).
• Hormonal therapy, with the exception of androgen deprivation therapy and stable regimens of prednisone and dexamethasone, (no change within 2 weeks prior to cycle1/day 1). Prior prostate hormonal treatment must have been discontinued at least four weeks (6 weeks for Casodex) prior to cycle1/day 1.
• Cardiovascular: Uncontrolled hypertension (resting blood pressure >160/100 mm/Hg); clinical episodes of congestive heart failure, angina pectoris, or myocardial infarction within the last year.
• Any active infections (requiring IV antibiotics).
• Any prior chemotherapy.
• Not reliable for adequate follow-up.
• History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
• Brain metastases or (clinical signs of) brain involvement or leptomeningeal disease.
• Patients with a history of another malignancy during the last 5 years other than prostate cancer, nonmelanomatous skin cancer or in situ bladder cancer (Stage T1a).
• Concurrent commercial or investigational antineoplastic therapy.