Safety and efficacy of maintenance therapy with a nonspecific cytochrome P17 inhibitor (CYP17i) after response/stabilization to docetaxel in metastatic castration-resistant prostate cancer - Abstract

BACKGROUND: Frontline treatment of metastatic castration-resistant prostate cancer (mCRPC) consists of docetaxel-based chemotherapy.

The median time to progression (TTP) from chemotherapy initiation is 6 to 8 months. Ketoconazole, a nonspecific cytochrome P17 inhibitor (CYP17i), blocks adrenal androgen synthesis. Low-dose ketoconazole (LDK), (200 mg three times daily [t.d.s]) has shown activity in mCRPC after progression to androgen deprivation. The role of a CYP17i after docetaxel treatment in the maintenance setting has been unexplored.

METHODS: We identified 38 patients with mCRPC who showed progression to luteinizing hormone releasing-hormone agonists (LHRHa) and who were treated with a median of 7 cycles of frontline three-weekly docetaxel (75 mg/m2) plus prednisone (10 mg/d) and LHRHa. Medical charts of 20 patients who showed no progression to docetaxel were reviewed. After the last docetaxel cycle, 10 patients received LDK maintenance treatment plus prednisone (10 mg/d) and LHRHa, whereas 10 patients received LHRHa alone. TTP was the primary endpoint.

RESULTS: After a follow-up of 27 months, disease in all patients receiving LHRHa alone progressed, whereas 8/10 patients progressed to maintenance therapy. Median TTP from docetaxel initiation was 11.5 months (95% confidence interval [CI], 6.3-16.6) for maintenance therapy and 9.2 months (95% CI, 8.5-9.9) for LHRHa alone (P = .047). The maintenance treatment was well tolerated. Only 1 patient experienced a grade 4 adverse event due to a nonsymptomatic pulmonary embolism.

CONCLUSION: This is the first study evaluating a CYP17i for maintenance therapy after docetaxel therapy. We showed a 2-month significant benefit in TTP for patients with mCRPC treated with LDK maintenance therapy after docetaxel, with a favorable toxicity profile. A large prospective randomized study using a CYP17i is warranted.

Written by:
Gil-Bazo I, Arévalo E, Castillo A, Zudaire ME, Carranza OE, Fusco JP, Castañón E, Collado-Gómez V, López I, Gil-Aldea I.   Are you the author?
Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain; Division of Oncology, Center for Applied Medical Research, Pamplona, Spain.

Reference: Clin Genitourin Cancer. 2012 Dec 20. pii: S1558-7673(12)00236-4.
doi: 10.1016/j.clgc.2012.11.003

PubMed Abstract
PMID: 23260990