952 - Sequential androgen deprivation and chemotherapy in metastatic prostate cancer: discordant responses in pilot study suggest an opportunity for indiv...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anticancer agents
Prostate Cancer
Therapy
Biological therapy
Presenter Ronald Tang
Authors R. Tang1, C. Piatek1, J. Pinski2, F. Acosta1, C. Korn1, D. Raghavan3, T.B. Dorff4, D.I. Quinn4
  • 1Medicine, University of Southern California, 90033 - Los Angeles/US
  • 2Medicine, University of Southern California, Keck School of Medicine, 90033 - Los Angeles/US
  • 3Carolinas Healthcare, Levine Cancer Institute, 28232 - Charlotte/US
  • 4Usc Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, 90033 - Los Angeles/US

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% & <10% gr4 CTCAE criteria toxicity. Pts ADT (androgen deprivation therapy) PSA nadir (PSAn) was correlated with MTX & DEC outcomes.

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.