927P - Time to progression and safety results of a nonspecific cytochrome-p 17 inhibitor after response/stabilization to docetaxel as a maintenance strateg...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Presenter Ignacio Gil-Bazo
Authors I. Gil-Bazo1, E. Arevalo2, A. Castillo1, M.E. Zudaire1, O.E. Carranza1, J.P. Fusco1, E. Castanon Alvarez3, L. Zubiri1, P. Martín1, I. Gil-Aldea4
  • 1Department Of Oncology, Clínica Universidad de Navarra, 31008 - Pamplona/ES
  • 2Clinical Oncology, Clínica Universidad de Navarra, 31008 - Pamplona/ES
  • 3Oncology Department, Clínica Universidad de Navarra, 31008 - Pamplona/ES
  • 4Centro De Investigación Biomédica, Complejo Hospitalario de Navarra, 31008 - Pamplona/ES

Abstract

Background

The first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) consists of docetaxel-based chemotherapy. The median time to progression (TTP) from chemotherapy initiation is 6-8 months (mo). Ketoconazole is a nonspecific cytochrome-P 17 inhibitor (CYP17i) that blocks adrenal androgen synthesis. Low-dose ketoconazole (LDK), (200 mg, t.d.s) has shown interesting activity in mCRPC after progression to androgen deprivation. The role of a CYP17i in the maintenance setting after response/stabilization to docetaxel has never been studied.

Methods

Thirty-eight mCRPC patients showing progression to luteinizing-hormone releasing hormone agonists (LHRHa), maintained LHRHa and received a median of 7 cycles of front-line three-weekly docetaxel (75 mg/m2) plus daily prednisone (10 mg). Twenty out of the thirty-eight patients showing no progression to docetaxel were enrolled. After docetaxel, ten patients were assigned to LDK maintenance treatment plus prednisone (10 mg/day) and LHRHa, and ten patients received LHRHa alone. TTP was the primary endpoint.

Results

After 33 months follow-up, a median TTP from docetaxel initiation was 11.5 months (IC95%: 6.3-16.6) for maintenance therapy and 9.2 months (IC95%: 8.5-9.9) for the control arm p = 0.047). Maintenance treatment was well tolerated with only one patient experiencing a grade 4 adverse event (non-symptomatic pulmonary embolism). Grade 1 and 2 asthenia and hot flashes worsening were the most common toxicities (table).

Conclusions

This is the first study testing a CYP17i for maintenance therapy after response/stabilization to docetaxel. A more than 2 months significant benefit in TTP with a favorable toxicity profile is observed. A further prospective analysis in a larger series using a CYP17i is warranted.

Toxicity profile of maintenance therapy with a CYP17 inhibitor.

Grade Toxicity 1 2 3 4 5
Asthenia 3 2 - - -
Diarrhea 1 1 - - -
Hepatotoxicity 1 1 - - -
Hyporexia - 1 - - -
Cephalea 1 - - - -
Hot flashes 1 4 - - -
Fluid Retention 1 2 - - -
Pulmonary embolism - - - 1 -

Disclosure

All authors have declared no conflicts of interest.