Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Concomitant Medication ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16100-e16100
Author(s):  
T. Koie ◽  
H. Yamamoto ◽  
A. Okamoto ◽  
S. Hatakeyama ◽  
A. Momose ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Objective Response ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Disease Free

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.

Efficacy and safety of valrubicin in non–muscle-invasive bladder cancer in older and younger patients.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 309-309
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Serious Adverse Event ◽  
Free Survival ◽  
Kaplan Meier ◽  
Muscle Invasive ◽  
Funding Research

309 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report the effectiveness and safety of valrubicin, stratified by patient age, from a US multicenter, observational, retrospective study. Methods: Medical records of adults with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted between March and September 2011. The median age (75 [range 42–95] years) was the stratification cutoff. Kaplan-Meier analyses were performed for event-free survival (EFS), worsening-free survival (WFS), and progression-free survival (PFS). Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 [range, 2–18] instillations). Median EFS, WFS, and PFS were similar in patients ≤75 vs >75 years old (see Table); 1-year rates were 17.8% vs 15.4%, respectively, for EFS; 16.1% vs 14.3% for WFS; and 80.2% vs 81.4% for PFS. 11 (19%) patients aged ≤75 years vs 4 (7%) aged >75 years underwent radical cystectomy; 28 (48%) vs 28 (51%), respectively, experienced ≥1 local adverse reaction; 3 (5%) vs 4 (7%) experienced ≥1 serious adverse event; and 4 (7%) vs 1 (2%) discontinued as a result. Conclusions: In patients with NMIBC treated with intravesical valrubicin, effectiveness and safety are similar in patients aged ≤75 and >75 years. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc. [Table: see text]

scholarly journals FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

2020 ◽  
Vol 9 (4) ◽  
pp. 994 ◽  
Author(s):  
Danijel Sikic ◽  
Markus Eckstein ◽  
Ralph M. Wirtz ◽  
Jonas Jarczyk ◽  
Thomas S. Worst ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Gene Panel ◽  
The Cancer Genome Atlas ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 (p = 0.0048) and KRT20 (p = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS (p = 0.0333) and RFS (p = 0.0310). FOXA1 expression (AUC = 0.79; p = 0.0007) was closest to the combined marker expression (AUC = 0.79; p = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC.

Germline DNA copy number polymorphism to predict the efficacy of BCG therapy for non-muscle invasive bladder cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 431-431
Author(s):  
Yoshiaki Yamamoto ◽  
Sho Ozawa ◽  
Masahiro Samoto ◽  
Junichi Mori ◽  
Ryo Inoue ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Copy Number ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Intravesical Instillation ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Bcg Therapy ◽  
Muscle Invasive

431 Background: Bacillus Calmette-Guerin (BCG) intravesical instillation is the most effective immunotherapy for non-muscle-invasive bladder cancer (NMIBC), however there are few reliable markers to elucidate the efficacy of BCG therapy. Germline copy number polymorphisms (CNPs) are expected to affect various diseases including human malignancies, but the significance of CNPs in NMIBC treated with BCG therapy remains unclear. FAM81A located on 15q22.2 was reported as one of tumor-associated ETS shared target genes in prostate cancer. PCSK6 located on 15q26.3 was reported to regulate proliferation and tumor progression in several cancers. The purpose of this study is to determine the prognostic value of CNPs for NMIBC treated with BCG therapy. To our knowledge, this is the first report to confirm CNPs as a potential biomarker for assessing the efficacy of immunotherapy. Methods: Array comparative genomic hybridization (CGH) was performed to search for candidate whole genome-wide CNPs related to NMIBC susceptibility. Next, quantitative real-time polymerase chain reaction was carried out to evaluate the effect of BCG therapy for 57 Japanese patients with NMIBC treated with BCG intravesical instillation. Results: Eleven CNPs were associated with NMIBC risk in array CGH. FAM81A and PCSK6 copy number according to those CNPs examined showed significant relationship with disease progression in NMIBC treated with BCG. The means of the relative copy numbers of patients with CNP and those without it were 1.58 and 2.10 for FAM81A ( P < 0.0001), and 1.06 and 1.80 for PCSK6 ( P < 0.0001), respectively. Univariate Cox proportional hazards regression analysis showed that FAM81A ( P = 0.0022), and PCSK6 ( P = 0.0147) copy number had a significant effect on progression-free survival. In multivariate analyses, FAM81A copy number was an independent prognostic factor for progression-free survival ( P = 0.0419, RR = 7.59, 95% CI, 1.07–153.42). The combination of FAM81A or PCSK6 CNP was the most significant prognostic biomarker to predict the efficacy of BCG therapy for NMIBC ( P = 0.0002). Conclusions: Germline DNA CNPs may be a potential new biomarker for estimating the efficacy of BCG therapy in Japanese patients with NMIBC.

scholarly journals Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin

2021 ◽  
Author(s):  
Florus C. de Jong ◽  
Teemu D. Laajala ◽  
Robert F. Hoedemaeker ◽  
Kimberley R. Jordan ◽  
Angelique C.J. van der Made ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Molecular Subtypes ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Clinical Tool ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

SummaryThe recommended treatment for patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. In case of progression to advanced disease, patients must undergo a radical cystectomy with significant morbidity and have a poor clinical outcome. Identifying tumors least likely to respond to BCG can translate into alternative treatments, such as early radical cystectomy or novel targeted or immunotherapies. Here we present molecular profiling of 132 BCG-naive, HR-NMIBC patients, and 44 post-BCG recurrences (34 matched), which uncovered three distinct BCG Response Subtypes (BRS1-3). Patients with BRS3 tumors have reduced recurrence and progression-free survival compared to BRS1-2. BRS3 tumors expressed high EMT-basal markers and had an immunosuppresive profile, which was confirmed with spatial proteomics. Tumors which recurred post-BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive HR-NMIBC patients and the molecular subtypes outperformed guideline recommended risk stratification based on clinicopathological variables. For clinical application, we validated that a commercially approved assay was able to accurately predict BRS3 tumors (AUROC 0.86). Our findings provide a potential clinical tool for improved identification of HR-NMIBC patients at the highest risk of progression, which can be used to select patients for early radical cystectomy or novel subtype-directed therapies.One Sentence SummaryMolecular subtypes are predictive of response to intravesical Bacillus Calmette-Guérin immunotherapy in non-muscle invasive bladder cancer.

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