Flu/TBI in Treating Patients Not Responding to Previous Hormone Therapy

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the prostate
• Metastatic and progressive disease
• Refractory to hormonal therapy
• Prostate-specific antigen (PSA) > 5 ng/mL
• Previously treated with a docetaxel-based regimen
• No CNS metastases

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 6 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin < 2 times upper limit of normal (ULN)
• AST and ALT < 4 times ULN

Renal

• Creatinine clearance > 50 mL/min

Cardiovascular

• LVEF > 35%
• No symptomatic congestive heart failure

Pulmonary

• DLCO > 40% of predicted OR
• Total lung capacity or FEV_1 > 30% of predicted

Other

• HIV negative

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics

PATIENT AND DONOR SELECTION CRITERIA

4.1 Patient Inclusion Criteria:

4.1.1 Males aged 18-75.

4.1.2 Pathologically proven adenocarcinoma of the prostate with metastases and progressive disease (new metastatic lesions or increase in cancer-related pain or a rising PSA defined by consensus criteria. (A rising PSA will be defined as 2 measurements higher than an initial value. The second of the 3 measurements must be at least 7 days after the first).

4.1.3 Progressive disease despite hormonal management (including antiandrogen withdrawal, 6 weeks for bicalutamide, 4 weeks for flutamide or nilutamide)

4.1.4 PSA > 5 ng/mL

4.1.5 Serum testosterone level < 50 ng/mL

4.1.6 Prior treatment with a docetaxel-based regimen.

4.1.7 Performance status: Karnofsky Performance Scale (KPS) 70-100%. (Appendix III).

4.1.8 Signed informed patient consent.

4.2 Patient Exclusion criteria:

4.2.1 Expected survival less than 6 months

4.2.2 Active central nervous system involvement or spinal instability

4.2.3 Organ dysfunction:

4.2.3.1 Cardiac: Ejection fraction <35% or symptomatic congestive heart failure.

4.2.3.2 Pulmonary: DLCO <40% of predicted or either TLC or FEV1 < 30% predicted.

4.2.3.3 Liver dysfunction: serum total bilirubin >2x upper limit of normal (ULN) or either ALT or AST >4x ULN

4.2.3.4 Renal dysfunction: creatinine clearance < 50 ml/min

4.2.4 HIV seropositivity

4.2 Related Donor Inclusion criteria:

4.3.1 Age 18-75

4.3.2 Related to the patient and genotypically or phenotypically HLA-identical. (Appendix IV)

4.3.3 Able to give consent to peripheral blood stem cell mobilization with G-CSF and apheresis collection. Bone marrow donors are not eligible.

4.3 Unrelated Donor Inclusion criteria:

4.4.1 Age 18-75.

4.4.2 Unrelated donors who are prospectively:

4.4.2.1 Matched for HLA-DRB1 and -DQB1 alleles by high resolution typing AND 4.4.2.2 Matched for all serologically recognized HLA-A or -B or -C antigens and at least five of six HLA-A or -B or -C alleles as defined by Appendix IV.

4.4.3 Able to give consent to peripheral blood stem cell mobilization with G-CSF and apheresis collection. Bone marrow unrelated donors are not eligible.

4.4 Related and Unrelated Donor Exclusion criteria:

4.5.1 Identical twin.

4.5.2 Any contraindication to the administration of G-CSF for mobilization.

4.5.3 Serious medical or psychological illness.

4.5.4 Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.

4.5.5 HIV seropositivity.

4.5.6 The donor is pregnant, has a positive serum ßhCG or is lactating.