Abiraterone acetate plus prednisone for the Management of Metastatic Castration-Resistant Prostate Cancer (mCRPC) without prior use of chemotherapy: report from a large, international, real-world retrospective cohort study.

BACKGROUND: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated. METHODS: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment. RESULTS: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range [IQR]: 69.0-81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2-133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2-11.1) and the median PFS was 10.8 months (95%CI: 9.6-11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001). CONCLUSIONS: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population.

Optimization of recombinant human erythropoietin therapy after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with prolonged anemia caused by defective erythropoietin (Epo) production. We enrolled 34 recipients of an allogeneic HSCT in three consecutive trials to determine the optimal utilization of recombinant human erythropoietin (rhEpo) therapy in this setting. MATERIALS AND METHODS: In the first trial (n = 7), rhEpo 1400 U/kg/week was given from day 1 until a hemoglobin (Hb) level of 10 g/dL was achieved, for a maximum of 60 days. In the second trial, rhEpo 500 U/kg/week was given to achieve Hb levels of 13 to 14 g/dL in 13 anemic patients with fatigue 56 to 1440 days after transplant. In the third trial, rhEpo was scheduled to start on day 35 in 14 patients at a dose of 500 U/kg/week with the aim of achieving Hb levels of 13 to 14 g/dL. RESULTS: In trial 1, erythroid recovery to 1% reticulocytes and red blood cell transfusion independence were faster, but the number of transfusions was not reduced compared to 10 controls. Responses were brisk in trial 2, with transfusion independence achieved after a median of 1 week in 12 of 13 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 6, 7, 10, and 10 weeks, respectively. Transfusions were significantly reduced in the first month of rhEpo therapy. In trial 3, transfusion independence was obtained after a median of 1 week in 13 of 14 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 3, 4, 6, and 8 weeks, respectively. Transfusions rates were considerably reduced compared to the previous month in the same patients or compared to controls undergoing peripheral blood or marrow transplant without rhEpo. CONCLUSIONS: Anemia after allogeneic HSCT is exquisitely sensitive to rhEpo. The benefit is minimal when it is given early post-transplant, as used in all trials to date. However, the rate of major response is greater than 90% when rhEpo is started after day 35. These data provide the basis on which to conduct a prospective, randomized, placebo-controlled trial of rhEpo therapy after allogeneic HSCT.