Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review.

BACKGROUND: Limited data are available for the use of agents in metastatic castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide data during treatment with cabazitaxel (CAB), helping to improve the informed-consent process. PATIENTS AND METHODS: We retrospectively reviewed patients treated with fourth-line or beyond CAB for mCRPC after failure of previous therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223. The progression-free survival (PFS) and the overall survival (OS) were estimated using the Kaplan-Meier method and compared to published data based on a structured literature review. The hospitalization rate was recorded. Factors influencing 6-months OS were analyzed. RESULTS: Fifteen patients were identified at 4 institutions and included in the analysis. The median PFS was 104 days (range 47-397 days). The median time to death was 10 months (range 2-16). PFS and OS data are in accordance with 17 published patients so far. During the therapy, eleven (73%) of the patients were hospitalized. Prostate-specific antigen (PSA, 500 units; hazards ratio [HR] 1.491, 95% CI 1.000-2.0175), white blood cell count (HR 0.425, 95% CI 0.108-0.952), hemoglobin (HR 0.6014, 95% CI 0.2942-1.0758), and alkaline phosphatase (100 units; HR 1.0964, 95% CI 1.000-1.2859) correlate with 6-months OS. CONCLUSIONS: CAB beyond the third-line is often accompanied by hospitalization. PFS is a significant proportion of the median time of OS. The baseline laboratory might be a good indicator for the decision between CAB and best-supportive care.

Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naïve castration-resistant prostate cancer.

BACKGROUND: Abiraterone Acetate (AA) represents a highly effective androgen-receptor (AR) axis targeted agent. Treatment with AA in castration-resistant prostate cancer (CRPC) may partly mediate neuroendocrine differentiation (NED) as an escape mechanism, which may have implications for the choice of sequential therapy in CRPC. We evaluated how treatment with AA influences circulating neuromediators chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (Pro-GRP) in chemotherapy-naïve CRPC patients. METHODS: We conducted an analysis in chemotherapy-naïve CRPC patients with clinical or radiographic progression of disease. A total of 35 patients were included at five institutions between February 2013 and December 2014. Sixteen of them had received AA. Serum samples were obtained before a docetaxel-based chemotherapy and analyzed in a reference laboratory. Univariable and multivariable analyses were performed to test the influence of AA treatment, its duration of treatment, and other clinicopathological variables on circulating neuromediators. RESULTS: CGA and NSE levels were above the upper limit of normal (ULN) in n = 20 (57.1%) and n = 13 (37.1%), respectively. Treatment with AA and duration of treatment were not associated with levels above the ULN (CGA and NSE) or higher levels (Pro-GRP) of neuromediators. CGA levels were associated with age (P = 0.092), lymph node metastasis (P = 0.014), duration of androgen deprivation therapy (ADT; P = 0.083), and intake of proton pump inhibitors (P = 0.069). Pro-GRP levels were significantly associated with PSA levels (P = 0.002). On multivariate analysis, CGA levels above the ULN were significantly correlated with ADT (P = 0.01) and intake of proton pump inhibitors (P = 0.03). CONCLUSIONS: Circulating neuromediators in chemotherapy-naïve CRPC patients were elevated in a high percentage of patients. ADT was found to be a relevant NED driver in this cohort. Our results may imply that patients with CRPC after first-line treatment with AA in CRPC are not at a higher risk for developing NED. The major limitation of the study represents the one-time analysis of neuromediators. Larger studies with serial blood measurements or biopsy analysis before and after treatment are needed to confirm our results.

Prospective Evaluation of Neuromediator Dynamics in Castration-Resistant Prostate Cancer Patients During Docetaxel.

AIM: Aim of the study was to detect small cell/neuroendocrine (SCNC) transformation in metastatic castration-resistant prostate cancer (mCRPC) that is a challenging procedure. We investigated the role of neuromediator dynamics as potential evidence of SCNC in patients undergoing docetaxel therapy. PATIENTS AND METHODS: A multi-institutional, prospective observational study was conducted. Patients undergoing docetaxel treatment were included. Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) were sequentially evaluated at predefined time points. Outcome measures were overall survival (OS), progression-free survival (PFS) and PSA nadir. RESULTS: Fifty-two patients were included. A general rise in CGA levels was observed. Patients with a high CGA rise (100%ULN: CGA ≥98.1ng/ml) between the 1st and 3rd cycle trended towards a decreased OS (p=0.0649) and showed a decreased PFS (p=0.0369). In multivariate analysis, continuous CGA rise correlated with PFS (p=0.0553; HR 1.136), but was not an independent predictor of OS. CONCLUSION: Patients with an early high CGA rise may demonstrate a subgroup with poor outcome due to underlying SCNC transformation. Monitoring of CGA appears to be an option worth considering.