intermittent chemotherapy with or without granulocyte-macrophage colony-stimulating factor (gm-csf) for metastatic hormone refractory prostate cancer (hrpc)

Conditions: Prostate Cancer

Summary: this is a two-arm, randomized phase ii study of intermittent chemotherapy with and without gm-csf. all patients will receive six 21-day cycles of docetaxel 75 mg/m2 on day 2 of each cycle and 5 mg prednisone twice a day on days 1-21. following six cycles of chemotherapy, eligible subjects will be randomized to no maintenance therapy or to maintenance gm-csf therapy. the gm-csf group dose schedule will be 250 mcg/m2 subcutaneous (sq) daily days 15-28 every 28 days. patients in both groups will continue until disease progression at which time gm-csf will be discontinued and chemotherapy will again be administered.


Eligibility criteria:
inclusion criteria: 1. age over 18 years 2. histologically documented adenocarcinoma of the prostate 3. progressive metastatic prostate cancer 4. castrate levels of testosterone (\<50 ng/ml) must be maintained 5. prior hormonal therapy or medications : patients who are receiving an anti-androgen, secondary hormonal therapy (i.e. ketoconazole, aminoglutethimide, megestrol acetate, diethylstilbestrol), 5-alpha reductase inhibitor (i.e. finasteride (proscar), dutasteride (avodart)) or herbal prostate medication (i.e. saw palmetto, pc-spes, pc-plus) must discontinue the drug by the date of initiation of chemotherapy on study 6. ≥ 4 weeks since major surgery and fully recovered 7. ≥ 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to ≤grade 1 8. ≥ 8 weeks since the last dose of strontium or samarium 9. sexually active patients must agree to use adequate contraception 10. karnofsky performance status ≥ 60% 11. life expectancy \>12 weeks 12. required initial laboratory values absolute neutrophil count \> 1500/ul platelets \> 100,000/ul hemoglobin \> 8.0 g/dl creatinine ≤ 2.0 x upper limit of normal bilirubin ≤upper limit of normal (uln) aspartate aminotransferase (ast) / alanine aminotransferase (alt) / alkaline phosphatase: ast and alt and alkaline phosphatase must be within the range allowing for eligibility in determining eligibility, the more abnormal of the 2 values (ast or alt should be used. an abnormal alkaline phosphatase must be attributed to liver dysfunction and not metastatic bone involvement (i.e elevated gamma-glutamyl transpeptidase (ggtp) or evidence of liver metastases) inclusion criteria for late enrolling patients: 1. age over 18 years 2. histologically documented adenocarcinoma of the prostate 3. ≤3 cycles of prior docetaxel chemotherapy for metastatic disease permitted prior to enrollment 4. docetaxel must have been administered on an every 3 week schedule 5. each docetaxel dose must have been between 60 and 75 mg/m2 6. castrate levels of testosterone \<50 ng/ml 7. daily use of other steroids (hydrocortisone, dexamethasone) instead of prednisone or no steroids, is permitted up until time of enrollment 8. a prostate-specific antigen (psa) level must have been documented within 6 weeks of initiating docetaxel chemotherapy exclusion criteria: 1. prior systemic chemotherapy for prostate cancer, other than q 3-week docetaxel/prednisone. prior neoadjuvant or adjuvant chemotherapy is permitted if there was no evidence of disease relapse within 12 months of the last dose of chemotherapy. 2. \>3 cycles of q3 week docetaxel/prednisone chemotherapy has already been administered to the patient 3. peripheral neuropathy \>grade 1 4. prior immunotherapy including systemic gm-csf or vaccines utilizing gm-csf; prior g-csf support of chemotherapy-related neutropenia is permitted 5. prior biologic agents (i.e.,anti-angiogenic agents, anti-epithelial growth factor receptor (egfr) inhibitors)≤ 4 weeks prior to registration 6. more than two prior therapies with an investigational agent, completed ≤ 4 weeks prior to enrollment (no prior immunotherapeutics are allowed) 7. myocardial infarction or significant change in anginal pattern within the last 6 months, symptomatic congestive heart failure (nyha class iii or higher) or uncontrolled cardiac arrhythmia 8. because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, hiv-positive patients receiving combination anti-retroviral therapy are excluded 9. patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 will be excluded 10. poorly controlled diabetes (fasting blood glucose \>250) despite optimization of medical therapy exclusion criteria for late enrolling patients: 1. prior immunotherapy including systemic gm-csf or vaccines utilizing gm-csf; prior g-csf support for chemotherapy-related neutropenia is permitted 2. delay of ≥6 weeks between any 2 chemotherapy cycles prior to enrollment on study 3. cumulative delays ≥8 weeks between chemotherapy cycles prior to enrollment on study

Keywords: metastatic hormone refractory prostate cancer