Background: Several APC show focal neuroendocrine (NE) spots at immunohistochemical analysis. CgA seems to be frequently associated to NE phenotype both in tissue and in circulation. Furthermore, high CgA levels during complete androgen blockade (CAB) therapy play a role in worsening prognosis of APC. Another point of interest is VEGF that is produced by NE cells and can stimulate neoangiogenic response of epithelial prostatic tissue. VEGF expression in NE cells is correlatedwith clinical characteristics and disease-specific survival. Somatostatin analogues induce a decrease in plasma CgA and may also exert anti-angiogenic activity indirectly by inhibition of VEGF, bFGF and GH/IGF-I axis. Methods: 40 APC patients, median age 75 (range: 65-83), were selected for hormone-refractory disease, previously treated with CAB. Serum PSA and plasmatic CgA and VEGF were performed in all pts at baseline (T0) and at 4 months (T4) and 8 months (T8) after therapy. Pts were also divided in group A (CgA T0 level > 18 U/l) and group B (CgA T0 level < 18 U/l). Group A was treated with docetaxel 75 mg/m2 every 3 weeks for 6 cycles and octreotide acetate 20 mg administered intramuscularly every 4 weeks until progression, group B with docetaxel only. Clinical and biochemical response, progression-free survival, toxicity and quality of life were also evaluated. Results: Evaluation was performed evaluated at the end of treatment. Median duration of treatment was 6 months (range: 4-12). Median duration of follow-up was 18 months (range: 8-32). 22 patients were included in group A: mean CgA plasma concentrations T0 78.7 U/l +/- 38.9, T4 43 U/l +/- 23.9, T8 31 U/l +/- 24.7; mean VEGF plasma concentrations T0 65.8 pg/ml +/- 31.3, T4 44.2 pg/ml +/- 20.9, T8 41.3 pg/ml +/- 15.6. 18 patients were included in group B: mean CgA plasma concentrations T0 12.9 U/l +/- 5.0, T4 15.6 U/l +/- 4.7, T8 19.8 U/l +/- 12.7; mean VEGF plasma concentrations T0 62.4 pg/ml +/- 30.1, T4 55.7 pg/ml +/- 26.6, T8 52.7 pg/ml +/- 26.7. PSA response rate (RR) was observed in 10/22 (45%) and 7/18 (39%) respectively for group A and B patients. Clinical objective RR was respectively 33% (7/22) and 22% (4/18). Only mild toxicities was observed in both groups. Conclusions: After therapy, only group A showed a statistically significant reduction of VEGF plasmatic levels (p < 0.05); also in group B lower levels of VEGF could be appreciated even if not statistically significant. It could suggest a crucial role of NE prostate cancer cells in VEGF expression. The combination therapy in patients with NE phenotype produces a significant reduction of plasma CgA levels as reported previously, with a favourable toxicity profile. Overall survival is still under evaluation. Further evaluations and a larger number of patients should be necessary to confirm these early observations.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA