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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.
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.
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).
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.