Abstract
4704 Background: Cox-2 expression has angiogenic and cytoprotective effects and its suppression could increase the response to chemotherapy. Cox-2 is overexpressed in 89.3% of pts with prostate cancer and it is an independent predictor of survival (Proc ASCO 2003,abst #1675). D and C exhibit antiangiogeneic activity and induce apoptosis. A combination of D and C could be synergistic. The objectives were to determine their effects on PSA, overall response (OR), toxicity, time to progression (TTP) and survival. Methods: Twenty eight (28) pts with HRPC progressing by rising PSA and scans were treated with D 30mg/m2 IV/wk over 30min for 3 wks and C 400mg po bid for 4 wk cycle. All were assessed by PSA and scans every 2 cycles. Dose modifications for hematology and renal toxicities were made. The RECIST criteria, PSA decline by ≥50% and the Simon’s Optimal Two-Stage design were used. Results: To date 28 pts have enrolled. Twenty seven (27) pts have received a minimum of 2 cycles, median (M) was 3 cycles (range 2–6) of D and C. One (1) pt received one cycle. The M age was 73 years (55–94), ECOG PS 1(0–1), LDH 186.5 U/L (125–899), Hgb 12.1 g/dL (8.6–14.6), PSA 93.6 ng/dL (15.3–4192). 81.5% of pts had soft tissue and 85.2% had bone metastases. Twenty seven (27) pts are evaluable for response. Of those, 11 pts (41%) had PSA response with normalization in 3 (11.1%); 6 pts (33.3%) had soft tissue response with 3 CR, 3 PR and 14 pts (51.9%) had stable disease. One (1) pt had major improvement on bone scan. OR was documented in 13 pts (48.2%). M TTP by PSA was 3.7 months (0.7 -10.8+) and by scans was 7.7 months (1.4 -14.9+). The M survival has not been reached after 12.5 months of follow up (3.0–17.8+). One pt withdrew due to abdominal discomfort, 2 pts (11.7%) had grade III diarrhea and 1 pt had grade III nail changes. There was excellent renal and cardiovascular tolerance. Conclusions: The combination of D and C is well tolerated. The OR rate was 48.2% with PSA normalization, soft tissue response and bone scan improvement. Longer follow up will determine the full impact of this active combination. Sponsored by Aventis Sanofi and Pfizer Pharmaceuticals. No significant financial relationships to disclose.
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