当前位置： SCI文献检索 > Clinical Genitourinary Cancer期刊下所有文献 > Safety and efficacy of maintenance therapy with a nonspecific cytochrome P17 inhibitor (CYP17i) after response/stabilization to docetaxel in metastatic castration-resistant prostate cancer.

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/m(2)) 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.

journal_name

Clin Genitourin Cancer

journal_title

Clinical genitourinary cancer

authors

Gil-Bazo I,Arévalo E,Castillo A,Zudaire ME,Carranza OE,Fusco JP,Castañón E,Collado-Gómez V,López I,Gil-Aldea I

doi

10.1016/j.clgc.2012.11.003

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

78-84

issue

2

eissn

1558-7673

issn

1938-0682

pii

S1558-7673(12)00236-4

journal_volume

11

pub_type

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