An Open Trial to Assess the Efficacy and Safety of Oral Thalidomide in Patients With Hormone-Refractory Prostate Cancer

Trial objectives: The primary objective is to determine the proportion of patients who have 50% decrease in PSA maintained for at least 4 weeks, in advanced hormone-refractory prostate cancer (HRPC) patients who receive thalidomide (100 mg BID). Secondary objectives include the objective tumor response rate for measurable lesions, the median duration of tumor response, median time to disease progression and assessments of clinical benefits, quality of life, and safety profile.

• Trial objectives: The primary objective is to determine the proportion of patients who have 50% decrease in PSA maintained for at least 4 weeks, in advanced hormone-refractory prostate cancer (HRPC) patients who receive thalidomide (100 mg BID). Secondary objectives include the objective tumor response rate for measurable lesions, the median duration of tumor response, median time to disease progression and assessments of clinical benefits, quality of life, and safety profile.
• Number of patient : about 70 evaluable patients
• Medication and Dose: Thalidomide (THADO 50mg/cap.) 100mg, BID.
• Duration: Continue treatment until disease progression, unacceptable toxicity or when patient meets any off-study criteria.
• Efficacy assessments: % of patients with 50% decrease in PSA maintained for at least 4 weeks,Objective tumor response Median duration of tumor response Median time to disease progression, Clinical benefits pain, performance status, weight
• Quality of life (evaluated by the instruments of EORTC-QLQ-C30, FACT-prostate)Safety assessments:
• Toxicity -Adverse Event -Laboratory Test

Inclusion Criteria:

• 18 years of age or older.
• Histologically or cytologically confirmed adenocarcinoma of prostate that is metastatic, hormone-refractory (confirmed by testing serum testosterone), and clinically progressive following at least one prior hormonal regimen.
• Patients must have documented progression of disease on anti-androgen withdrawal, if the patient have documented progression on previous anti-androgen therapy.
• Measurable (patient with measurable bi-dimensional disease) or evaluable disease (defined as the presence of a nonmeasurable abnormality on CT or on physical examination coupled with a PSA ³ 30).
• Karnofsky performance status ³ 60%.6. Adequate bone marrow functions: Granulocyte count 1,000/mm3, Platelets 75,000/mm3, haemoglobin 8 g/dl.
• Adequate renal and liver functions: Creatinine < 1.5 mg/dl, Bilirubin < 2 mg/dl, ALT/AST less than 2.5 times the upper limit of the reference range for the institute.
• Patients with chemical or clinical hypothyroidism should have their thyroid replacement prior to starting study.
• Patients must have recovered from the effect of recent surgery (at least 4 weeks apart), radiotherapy (at least 4 weeks apart).
• Patients have ability to complete Quality of Life (QoL) questionnaires.
• Patients must sign informed consent.

Exclusion Criteria:

• Patients with advanced second primary malignancy.
• Patients with brain metastases.
• Patients with hypersensitivity to thalidomide.
• History of myocardial infarction within past 6 months, uncontrolled congestive heart failure or angina pectoris.
• Patients with orthostatic hypotension before therapy.
• Patients with NCI CTC grade 3 or greater peripheral neuropathy of any cause that is clinically detectable.
• Patients with active infection, including positive serology for HIV.
• Patients who have received chemotherapy before for treatment of metastases of prostate cancer, or received other investigational agents or corticosteroids within 4 weeks prior to enrollment of study.

• National Taiwan University Hospital
• Taipei Veterans General Hospital,Taiwan
• Chang Gung Memorial Hospital
• Mackay Memorial Hospital
• Tri-Service General Hospital
• China Medical University Hospital
• Chi Mei Medical Hospital
• Buddhist Tzu Chi General Hospital