Impact of PSA flare-up in patients with hormone-refractory prostate cancer undergoing chemotherapy.
OBJECTIVE
The intention of this study is to describe the impact and underlying potential basis of the prostate-specific antigen (PSA) flare-up phenomenon in patients with hormone-refractory prostate cancer (HRPC) treated with docetaxel-based chemotherapy.


METHODS
We retrospectively identified 74 consecutive patients who received docetaxel/estramustine-based chemotherapy at our institution. Patients were evaluated based on modified criteria from the Prostate-Specific Antigen Working Group regarding survival and toxicity. Additionally, two androgen receptor mutations derived from patients with advanced disease were analyzed for promiscuous transactivation activity.


RESULTS
The 74 patients were stratified into four groups: response, partial response, flare-up-initial PSA elevation, and progression. Median survival in the flare-up group (n=8) was 20 months and did not differ from the response group (p=0.564). The flare-up group showed a maximum PSA elevation from baseline between 3.4 and 28.3% (between three and six weeks) followed by PSA decline >or=50% from the baseline level in seven of the eight patients. The androgen receptor mutations AR(877) and AR(715) displayed a 37.5- and 5.2-fold increase in transactivation activity by progesterone and a 12.6- and 5.4-fold increase by estrogen compared to the AR(WT), respectively.


CONCLUSIONS
A considerable portion of HRPC patients experience an initial PSA flare-up under systemic chemotherapy. In this study, occurrence of flare-up phenomenon did not impact survival. Chemotherapy should be continued a minimum of six weeks before removing patients from a docetaxel-based regimen. We showed evidence that co-medication with dexamethasone/prednisolone and/or estramustine itself can induce an initial PSA flare-up via androgen receptor mutations.
Nelius
Thomas
T
Department of Urology, Texas Tech University Health Sciences Center, Medical Office Plaza, Suite 260, 3502 9th Street, Lubbock, TX 79415, USA. thomas.nelius@ttuhsc.edu
Klatte
Tobias
T
de Riese
Werner
W
Filleur
Stephanie
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000368:Aged; D000728:Androgens / Q000502:physiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D011944:Receptors, Androgen / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000728:Androgens; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D017430:Prostate-Specific Antigen