952 - Sequential Androgen Deprivation and Chemotherapy in Metastatic Prostate Cancer: Discordant Responses in Pilot Study Suggest an Opportunity for Individualized Therapy

Abstract

ABSTRACT Background CRPC is fatal but with recent better survival based on new agents. Optimal sequential therapy remains a challenge. We undertook a phase II pilot study of Mitoxantrone (MTX) followed by docetaxel, estramustine, carboplatin (DEC). Methods CRPC pts who progressed on/after MTX were given estramustine 280mg TID x 5d, docetaxel 60mg/m2, carboplatin AUC = 5 q28 days; ASA & warfarin daily, max 8 cycles. Endpoints: RR >30% with PSA fall >30% & Results 20 pts: Med. age: 66 yrs (53-83), Med. Gleason 8, ECOG PS: 0-1, 12 pts with RP and 8 pts de novo mets, Sites: bone (18), lung (3), liver (4), LN (6). Pts received 2-11 MTX cycles. Prior RT: 12 pts. On DEC 13/20pts PR by PSA, 5: SD, 1: PD; 1: NE. Toxicity: 9pts gr 3/4 neutropenia - 1 with fever, 3: gr 3 neuropathy, 3: gr3 infection, 6: gr 3/4 Hgb, 1: gr3 plats, 1 DVT. Non-heme tox: 4pts gr3 fatigue, 3: gr 3 UTI, 1 gr3 dehydration & diarrhea. Med PFS MTX: 5.5 mos (1.2, 15.3), Med PFS DEC: 5.3 mos (1.2-14.5). OS from MTX start: 20.3 mos (9.1-37.5). OS from DEC start: 12.3 mos (1.2-31). Regression analysis identified visceral mets, alk phos & PFS on MTX (but not PSA, ECOG, Hb or Gleason score) as independent factors for OS from start of MTX. Response to MTX & DEC only partly overlapped. PSA response >30% drop in PSA to MTX or DEC & median OS were: responders to MTX only (n = 4; 20.3 mos (18.4-25.4)); to docetaxel only (n = 10; 14.6 mos (9.1-43.7); both (n = 5; 28.9 mos (22.7-40.3); neither (n = 1; 12.3 mos (Fisher's exact p = 0.3 for response MTX vs DEC, logrank p = 0.028 for OS). Based on pts ADT PSAn, we found longer PFS for DEC and MTX with higher PSAn (log-rank p = 0.048 & 0.019) & trend to better OS on MTX/DEC sequence with PSAn >4 (p = -0.14, med OS 20.1 vs 25.8 months). Fall in Hgb between ADT & start of DEC associated with shorter PFS on DEC (p = 0.05) with a trend to shorter OS (p = 0.08). Conclusions DEC was effective in patients with CRPC given MTX. Pts benefited if they responded to either or both agents but there was limited overlap in response (25%). High PSA nadir on ADT maybe associated with a longer PFS & OS to chemotherapy. Biomarkers linked to hormonal & chemotherapy effect for individual agents in PC could have significant utility. Study with larger cohorts of sequential therapy is ongoing Disclosure All authors have declared no conflicts of interest.