Re: Anti-Inflammatory Use May Not Negatively Impact Oncologic Outcomes following Intravesical BCG for High-Grade Non-Muscle-Invasive Bladder Cancer

2017 ◽  
Vol 198 (5) ◽  
pp. 978-980
Author(s):  
Sam S. Chang
Keyword(s):  
Bladder Cancer ◽  
Oncologic Outcomes ◽  
Invasive Bladder Cancer ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Intravesical Bcg ◽  
Anti Inflammatory ◽  
Muscle Invasive

scholarly journals Rapamycin enhances BCG-specific γδ T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study

2021 ◽  
Vol 9 (3) ◽  
pp. e001941
Author(s):  
Niannian Ji ◽  
Neelam Mukherjee ◽  
Ryan M Reyes ◽  
Jonathan Gelfond ◽  
Martin Javors ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Γδ T Cells ◽  
Percentage Change ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Double Blind ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Muscle Invasive

BackgroundAlthough intravesical BCG is the standard treatment of high-grade non-muscle invasive bladder cancer (NMIBC), response rates remain unsatisfactory. In preclinical models, rapamycin enhances BCG vaccine efficacy against tuberculosis and the killing capacity of γδ T cells, which are critical for BCG’s antitumor effects. Here, we monitored immunity, safety, and tolerability of rapamycin combined with BCG in patients with NMIBC.MethodsA randomized double-blind trial of oral rapamycin (0.5 or 2.0 mg daily) versus placebo for 1 month was conducted in patients with NMIBC concurrently receiving 3 weekly BCG instillations (NCT02753309). The primary outcome was induction of BCG-specific γδ T cells, measured as a percentage change from baseline. Post-BCG urinary cytokines and immune cells were examined as surrogates for local immune response in the bladder. Secondary outcomes measured were adverse events (AEs) and tolerability using validated patient-reported questionnaires.ResultsThirty-one patients were randomized (11 placebo, 8 rapamycin 2.0 mg, and 12 rapamycin 0.5 mg). AEs were similar across groups and most were grade 1–2. One (12.5%) patient randomized to 2.0 mg rapamycin was taken off treatment due to stomatitis. No significant differences in urinary symptoms, bowel function, or bother were observed between groups. The median (IQR) percentage change in BCG-specific γδ T cells from baseline per group was as follows: −26% (−51% to 24%) for placebo, 9.6% (−59% to 117%) for rapamycin 0.5 mg (versus placebo, p=0.18), and 78.8% (−31% to 115%) for rapamycin 2.0 mg (versus placebo, p=0.03). BCG-induced cytokines showed a progressive increase in IL-8 (p=0.02) and TNF-α (p=0.04) over time for patients on rapamycin 2.0 mg, whereas patients receiving placebo had no significant change in urinary cytokines. Compared with placebo, patients receiving 2.0 mg rapamycin had increased urinary γδ T cells at the first week of BCG (p=0.02).ConclusionsFour weeks of 0.5 and 2.0 mg oral rapamycin daily is safe and tolerable in combination with BCG for patients with NMIBC. Rapamycin enhances BCG-specific γδ T cell immunity and boosts urinary cytokines during BCG treatment. Further study is needed to determine long-term rapamycin safety, tolerability and effects on BCG efficacy.

Intravesical BCG induces a trained immunity phenotype in patients with non-muscle invasive bladder cancer

2021 ◽  
Vol 79 ◽  
pp. S615-S616
Author(s):  
J.H. van Puffelen ◽  
B. Novakovic ◽  
L. Van Emst ◽  
J.L. Boormans ◽  
E. Oosterwijk ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Trained Immunity ◽  
Intravesical Bcg ◽  
Muscle Invasive

scholarly journals Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer

2017 ◽  
Vol 89 (2) ◽  
pp. 102 ◽  
Author(s):  
Ali Serdar Gözen ◽  
Paolo Umari ◽  
Walter Scheitlin ◽  
Fuat Ernis Su ◽  
Yigit Akin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Recurrent Disease ◽  
Bladder Wall ◽  
Invasive Bladder Cancer ◽  
Outpatient Basis ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. Materials and methods: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. Results: Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. Conclusions: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

scholarly journals Does the Urinary Mast Cell Mediators Predict the Immune Response to BCG in Patients with Primary High-Grade Non-Muscle Invasive Bladder Cancer?

2020 ◽  
Author(s):  
Muhammed Fatih Simsekoglu ◽  
İslim Kaleler ◽  
Bulent Onal ◽  
Cetin Demirdag ◽  
Sinharib Citgez ◽  
...  
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
Mast Cell ◽  
Critical Role ◽  
Invasive Bladder Cancer ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Healthy Participants ◽  
Bcg Instillation

Background: Mast cells play a critical role in tumor-associated immune pathways. We aimed to determine whether the urinary mast cell mediators predict the immune response in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Methods: Nineteen patients who have received immunotherapy due to NMIBC and 19 healthy participants were enrolled. Urine samples were collected to assay N-methylhistamine, histamine, and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and four weeks after the sixth instillation in patients with NMIBC and at a single visit in healthy participants. Cystoscopic examinations were performed on the patient with NMIBC at three-month intervals for two years. The changes in urinary markers due to BCC response, BCG instillation, and the presence of NMIBC were assessed. Results: The average age was 56.1 ± 10.5 years in patients with NMIBC. Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1 tumors. While 12 patients responded, 6 presented with recurrence and 1 with progression. There was no correlation between the levels of mast cell mediators and BCG response. The N-methylhistamine and histamine levels were increased significantly with the onset of immunotherapy, and N-methylhistamine levels were significantly decreased when immunotherapy was terminated. Pre-BCG estimated marginal means of N-methylhistamine were significantly higher in patients with NMIBC than healthy participants. Conclusions: Our study is the first study to identify the changes in mast cell mediators with the onset of immunotherapy and with the presence of bladder cancer. However, these mediators were not found to predict the patients’ response to immunotherapy.

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