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Adaptive responses of androgen receptor signaling in castration-resistant prostate cancer

Perner S, Cronauer MV, Schrader AJ, Klocker H, Culig Z, Baniahmad A.

Abstract
 

BACKGROUND:

Randomized studies have shown improved survival with the combination of docetaxel (D) and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively investigated whether coadministration of low-dose glucocorticoids has clinical benefits.

MATERIAL AND METHODS:

Records from 358 patients with metastatic castration-resistant prostate cancer treated consecutively with either D 75mg/m(2) every 3 weeks (n = 124) (Rigshospitalet) or D and prednisolone (P) 10mg daily (n = 234) (Herlev Hospital) given as first-line chemotherapy were reviewed. Of these, 15 patients treated with glucocorticoids at initiation of D at Rigshospitalet were excluded. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was used to register any grade of peripheral edema, grade ≥2 sensory neuropathy, and grade ≥3 nonhematological toxicity. Background clinical data, rates of toxicity, hospital admissions, dose reductions, and post-D treatments were analyzed by the Chi-squared test or Mann-Whitney U test. Progression-free survival and overall survival were calculated by the Kaplan-Meier method.

RESULTS:

Patients treated with D alone had a higher incidence of peripheral edema (32% vs. 15%, P<0.001) and grade 3 nonhematological toxicity (56% vs. 43%, P = 0.022). Patients treated with D alone were also more frequently hospitalized (53% vs. 41%, P = 0.035), mainly owing to a higher incidence of febrile neutropenia in this group (25% vs. 10%, P<0.001). P did not influence progression-free survival (P = 0.692, log-rank test) or overall survival when adjusting for baseline levels of hemoglobin, alkaline phosphatase, lactate dehydrogenase, prostate-specific antigen, and Eastern Cooperative Oncology Group performance status (hazard ratioP = 0.98, 95% CI: 0.76-1.26, P = 0.89, Cox proportional hazard regression model).

CONCLUSIONS:

Coadministration of low-dose P reduced the incidence of peripheral edema, grade 3 nonhematological toxicity, and the risk of being admitted owing to febrile neutropenia during treatment with D. Adjusted survival analysis did not indicate that P affected prognosis.


©PubMed Central

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