A randomized phase II clinical trial of personalized peptide vaccination with metronomic low-dose cyclophosphamide in patients with metastatic castration-resistant prostate cancer

This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV. Seventy patients with metastatic castration-resistant prostate cancer were randomly assigned (1:1) to receive PPV plus oral low-dose CPA (50 mg/day), or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 pooled peptides according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL) and immunoglobulin G responses were measured before and after PPV. The incidence of grade 3 or 4 hematologic adverse events was higher in the PPV plus CPA arm than in the PPV alone arm. Decrease in Treg and increase in MDSC were more pronounced in PPV plus CPA treatment than in PPV alone (p = 0.036 and p = 0.048, respectively). There was no correlation between the changes in Treg or MDSC and CTL response. There was no difference in positive immune responses between the two arms, although overall survival in patients with positive immune responses was longer than in those with negative immune responses (p = 0.001). Significant differences in neither progression-free survival nor overall survival were observed between the two arms. Low-dose CPA showed no change in the...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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The objective of this study was to characterize the population pharmacokinetics of apalutamide and its metaboliteN-desmethyl-apalutamide in healthy male and castration-resistant prostate cancer subjects.MethodsPlasma concentration data for apalutamide and N-desmethyl-apalutamide from 1092 subjects (seven clinical studies) receiving oral apalutamide (30 –480 mg) once daily were pooled for a population pharmacokinetic analysis using a non-linear mixed-effect modelling approach. The impact of clinically relevant covariates was also assessed.ResultsApalutamide absorption was rapid, and the apparent steady-state volu...
Source: Clinical Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research
TAK ‐385 is an orally active gonadotropin‐releasing hormone (GnRH) antagonist with rapid testosterone‐lowering effects in clinical studies, achieving effective and sustained castration in patients with prostate cancer without the initial testosterone surge observed with GnRH agonists. To date, cli nical trials of TAK‐385 for the treatment of prostate cancer have been conducted in a predominantly Western patient population. Building on these data, the current study establishes an appropriate dose range for TAK‐385 in Japanese patients with non‐metastatic prostate cancer, and evaluates sa fety, pharmacokinetics, ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
CONCLUSIONS: Based on safety and tolerability, mivebresib RP2D is 1.5mg for the daily schedule, 2.5mg for 4/7 and 3mg for M-W-F. Mivebresib has a tolerable safety profile and stable disease was observed in some patients with malignant solid tumors. PMID: 31420359 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionsAfter treatment with AA or ENZ, elderly prostate cancer patients with pre-existing CVDs experienced higher short-term mortality than otherwise similar patients without CVDs. Mortality associated with CVDs did not depend on having received AA versus ENZ.Patient summaryPatients with pre-existing cardiovascular diseases (CVDs) experienced higher short-term mortality after abiraterone acetate or enzalutamide than those without pre-existing CVDs. It is recommended that a multidisciplinary team, including a cardiologist, evaluate patients having pre-existing CVDs in the process of making treatment decisions and monito...
Source: European Urology - Category: Urology & Nephrology Source Type: research
AbstractThe aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant prostate cancer (CRPC) before, between, and after standard chemotherapy, such as docetaxel and cabazitaxel, and new hormonal treatments, such as abiraterone and enzalutamide. A retrospective analysis was performed on 37 patients. Cyclophosphamide was given orally 50  mg per day together with low dose of corticosteroids, namely dexametasone orally 1 mg per day or prednisone 10 mg per day. Seventeen patients (51%) showed a PSA decline≥&thi...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsOverall risk of cancer in our MS cohort did not significantly differ from the controls. However, the age at diagnosis of breast cancer was statistically significantly higher among the MS patients in comparison with a control population from the same patient pool. Further population-based larger studies spanning longer follow-up periods and longer exposure to emerging MS therapies are needed to evaluate cancer risk related to MS treatments and breast cancer risk in particular.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Objective: To evaluate the occurrence of nonsyndromic cleft lip and/or palate (NSCL/P) in families of patients with prostate cancer (PC).Study design: We conducted a case-control study involving a total of 748 individuals, 280 of which had PC, and 468 were free-cancer healthy individuals. The patients answered a questionnaire with basic demographic information and family history of NSCL/P in first-degree relatives. The information collected was stored in a database and analyzed by using the statistical program SPSS® 24.0for Windows (Chicago, IL, USA). In order to determine the association with NSCL/P, chi-square and Fi...
Source: Dentistry 3000 - Category: Dentistry Source Type: research
Prostate-specific membrane antigen (PSMA)-targeted PET tracers have improved early detection of oligometastatic (OM) prostate cancer. Evidence suggests that stereotactic ablative radiotherapy (SABR) for OM prostate cancer may improve clinical outcomes, but localization of multiple small lesions for treatment is challenging with conventional X-ray-based imaging systems, limiting deliverable doses. Biologically-guided radiotherapy (BgRT) is being developed to utilize strong contrast of PET signal for real-time intra-fraction tracking of multiple targets.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Oral Abstracts Source Type: research
Conclusion: The safety profile of cabazitaxel in this pooled analysis of two cabazitaxel early access programmes was manageable and consistent with previous Phase III trials (TROPIC, PROSELICA). PMID: 31289614 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Conclusion: This study showed that periodontal diseases were associated with increased risk of several cancers. Besides other wellknown benefits for health, the provision of oral/dental health should be considered and employed as a cancer prevention measure. PMID: 31195790 [PubMed - as supplied by publisher]
Source: Turkish Journal of Medical Sciences - Category: General Medicine Tags: Turk J Med Sci Source Type: research
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