Docetaxel and sunitinib will be compared to docetaxel for their effect on CEC/CEP spikes induced by docetaxel in HRPC patients

Docetaxel (75mg/m2 q21d) is standard of care for patients with hormone refractory prostate cancer (HRPC). Recent data indicate, that chemotherapeutics given at MTD induce, besides their cytotoxic effects, mobilization of circulating endothelial cells (CEC) and - progenitors (CEP) in drug-free breaks of each cycle. In preclinical models, mobilized CEC/CEP result in tumor vasculogenesis and progression of disease.

We hypothesize that treatment with sunitinib, an anti-angiogenic tyrosine kinase inhibitor, in between 3 weekly docetaxel disrupts CEC/CEP spikes following docetaxel leading to chemosensitization and reduced tumor re-growth in HRPC patients responding to docetaxel.

• Drug: Docetaxel * Sunitinib
• Drug: Docetaxel

• Active Comparator: docetaxel 75mg/m2 day1 q 21d x 4 cycles, sunitinib 37.5mg/d day2 -day15 x 4 cycles
• Active Comparator: docetaxel 75mg/m2 day1 q 21d x 4 cycles

Inclusion Criteria:

• WHO performance status of 0-2.
• Histologically proven prostate adenocarcinoma.
• All patients must have prostate adenocarcinoma that is unresponsive or refractory to androgen ablation with biochemical progression

• Measurable and/or evaluable progressive disease, which is defined by one of the following three criteria:

  • 25% increase in bidimensionally measurable soft tissue metastases
  • Appearance of new metastatic lesions (proven by CT scan, X-ray or bone scan)
  • PSA level of at least 10ng/mL, with increases on at least 2 successive occasions at least 2 weeks apart
• If the patient has been treated with antiandrogens, treatment must have been stopped at least 6 weeks prior to study randomization