title: Low-dose prednisolone in first-line docetaxel for patients with metastatic castration-resistant prostate cancer: is there a clinical benefit?
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.
  
  
  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.
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Electronic address: per.kongsted@regionh.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Kongsted
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Lindberg
authors.affiliation: Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sengeløv
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D011239:Prednisolone
keywords: Docetaxel; Prednisolone; Prostate cancer; Toxicity; mCRPC