924 PREDICTION OF PROGRESSION-FREE SURVIVAL IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR LOCALLY ADVANCED BLADDER CANCER USING A SNP PANEL OF CANCER-ASSOCIATED GENES

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Takamitsu Inoue ◽  
Shigeyuki Matsui ◽  
Norihiko Tsuchiya ◽  
Kazuyuki Numakura ◽  
Susumu Akihama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Advanced Bladder Cancer ◽  
Snp Panel

Adjuvant Cisplatin Plus Methotrexate Versus Methotrexate, Vinblastine, Epirubicin, and Cisplatin in Locally Advanced Bladder Cancer: Results of a Randomized, Multicenter, Phase III Trial (AUO-AB 05/95)

2005 ◽  
Vol 23 (22) ◽  
pp. 4963-4974 ◽  
Author(s):  
Jan Lehmann ◽  
Margitta Retz ◽  
Christina Wiemers ◽  
Joachim Beck ◽  
Joachim Thüroff ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Who Grade ◽  
Free Survival ◽  
Advanced Bladder Cancer ◽  
Grade 3

Purpose Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy. Patients and Methods A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm2 on day 1 and methotrexate 40 mg/qm2 on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm2 on days 1, 15, and 22, vinblastine 3 mg/qm2 on days 2, 15, and 22, epirubicin 45 mg/qm2 on day 2, and cisplatin 70 mg/qm2 on day 2 of a 28-day cycle (M-VEC). Results The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (α = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates ± SE) for CM versus M-VEC were 46.3% ± 4.6% v 48.8% ± 4.5%, 52.0% ± 4.6% v 52.3% ± 4.8%, and 46.1% ± 4.3% v 45.1% ± 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001). Conclusion CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.

Prospective trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 515-515
Author(s):  
Mohamed S. Zaghloul ◽  
John Paul Christodouleas ◽  
Tarek Zaghloul ◽  
Andrew Smith ◽  
Ahmed Abdalla ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Prospective Trial ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
Advanced Bladder Cancer ◽  
Grade 3

515 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemo or decline it. Adjuvant radiotherapy (RT) is an alternative (or complementary) adjuvant therapy, but is rarely performed, with most of these patients being observed. In a prospective trial, we compared RT vs adjuvant chemo & hypothesized that RT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial at the National Cancer Institute (Cairo) compared adjuvant RT (standard of care in Egypt) vs. chemo+RT after RC for LABC. A 3rd arm, adjuvant chemo, was added later (gemcitabine/cisplatin x 4). Herein, we report results of RT vs adjuvant chemo. Patients ≤70 y/o with ≥1 of the following (pT3b/T4a, grade 3 or pN+) with negative margins after RC were eligible. RT was delivered with 3-D conformal RT to the pelvis (45 Gy in 1.5 Gy BID). Routine follow-up & pelvic CT q 6 months were performed. Post hoc non-inferiority exploratory analysis was performed. Results: 123 were enrolled (78 RT/45 chemo). 51% had urothelial carcinoma; 49% had squamous cell carcinoma. The arms were well-balanced except for gender (p=0.06). Two-year outcomes & overall adjusted hazard ratios (HR) for RT vs chemo were 54% vs 47% for DFS [HR 0.65(95%CI 0.35-1.19, p=0.16]; 92% vs 69% for local-regional recurrence-free survival [HR 0.28(95%CI 0.10-0.82), p=0.02]; 75% vs 79% for distant metastasis-free survival [HR 2.39(95%CI 0.94-6.09), p=0.07]; 61% vs 60% for overall survival [HR 0.94(95%CI 0.52-1.69), p=0.83]. In the urothelial cohort, there were no differences in DFS or OS. Late grade ≥3 GI toxicity was observed in 6 RT patients (8%) & 1 chemo patient (2%). Based on our data, there is a >90% probability that the true difference in 2-year DFS is <10%, the prespecified non-inferiority margin. Conclusions: This prospective study demonstrates that adjuvant RT has superior local control vs adjuvant chemo with no statistically significant differences in DFS or OS. Results suggest that RT can be an option for patients with LABC after RC where an alternative to chemo is desired by the patient or physician. Clinical trial information: NCT01734798.

Adjuvant chemotherapy is associated with decreased mortality after radical cystectomy for locally advanced bladder cancer

2014 ◽  
Vol 32 (6) ◽  
pp. 1463-1468 ◽  
Author(s):  
Daniel A. Yelfimov ◽  
Igor Frank ◽  
Stephen A. Boorjian ◽  
Prabin Thapa ◽  
John C. Cheville ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Adjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Advanced Bladder Cancer

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.

Randomized trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4507-4507 ◽  
Author(s):  
Mohamed S. Zaghloul ◽  
John Paul Christodouleas ◽  
Tarek Zaghloul ◽  
Andrew Smith ◽  
Ahmed Abdalla ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bladder Cancer ◽  
Adjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
Advanced Bladder Cancer ◽  
Grade 3

4507 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemotherapy or decline it, even though such treatment may be warranted. There is no clear alternative adjuvant therapy for these patients, who are usually observed. In this study, we compare post-op radiotherapy (PORT) vs. adjuvant chemotherapy in a randomized clinical trial. We hypothesized that PORT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial was opened to compare PORT vs. sequential chemo+PORT after RC for LABC & accrued from 2002–2008 at the NCI in Cairo. In 2007, a third arm comparing adjuvant chemo was added. Herein, we report the results of PORT vs. adjuvant chemo. Patients ≤70 y/o with ≥1 of the following factors (≥pT3b/T4a, grade 3, or positive nodes) with negative margins after RC + pelvic node dissection were eligible. Routine follow-up & pelvic CT q6 months were performed. PORT included 3D conformal pelvic RT (45Gy/1.5Gy BID). Chemo included gemcitabine/cisplatin x 4. Post-hoc non-inferiority exploratory analysis was performed. Results: The PORT arm accrued 78; the chemo arm accrued 45. 51% had urothelial carcinoma; 49% had squamous cell carcinoma/other. The two arms were well-balanced except for gender (p = 0.06). Two-year outcomes & overall adjusted hazard ratios (HR) for PORT vs. chemo alone were 54% vs. 47% (HR 0.65(95%CI 0.35-1.19, p = 0.16) for DFS; 92% vs. 69% (HR 0.28(95%CI 0.10-0.82), p = 0.02 for LRFS; 75% vs. 79% (HR 2.39(95%CI 0.94-6.09), p = 0.07) for DMFS; 61% vs. 60% (HR 0.94(95%CI 0.52-1.69), p = 0.83) for OS. Late grade ≥3 GI toxicity was observed in 6 PORT patients (8%) & 1 chemo patient (2%). Based on our data, there is a greater than 90% probability that the true difference in 2 yr DFS is less than 10%, the pre-specified non-inferiority margin. Conclusions: This randomized study demonstrates superior local control with PORT vs. adjuvant chemo with no significant differences in DFS, DMFS or OS. Results suggest that PORT could be an option for patients with LABC after RC who are medically unfit for adjuvant chemo or who decline it. Clinical trial information: NCT01734798.

Prospective trial of adjuvant therapy after radical cystectomy for locally advanced bladder cancer: Analysis of the squamous cell carcinoma subgroup.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 524-524
Author(s):  
Mohamed S. Zaghloul ◽  
John Paul Christodouleas ◽  
Tarek Zaghloul ◽  
Ahmed Abdalla ◽  
Hany William ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Adjuvant Therapy ◽  
Cell Carcinoma ◽  
Radical Cystectomy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Limited Efficacy ◽  
Advanced Bladder Cancer ◽  
Post Hoc

524 Background: The role of adjuvant therapy after radical cystectomy (RC) is not well-defined for squamous cell carcinoma (SqCC) of the bladder. Several studies suggest limited efficacy for chemo while adjuvant RT improved disease-free survival (DFS) vs. observation in a previous trial. In this study, we report a post-hoc subgroup analysis of SqCC to compare adjuvant therapies. We hypothesized that adjuvant RT would improve DFS vs. chemo for locally advanced bladder cancer (LABC) (≥pT3N0-N+). Methods: A randomized phase III trial was opened to compare adjuvant RT vs. sandwich chemo+RT after RC for LABC at the NCI in Cairo. A 3rd arm, adjuvant chemo, was added later. Bladder cancer patients ≤70 y/o with ≥1 of the following (pT3b/pT4a, grade 3, or pN+) with negative margins after RC were eligible. RT was delivered to the pelvis with 3D conformal RT (45Gy in 1.5Gy BID). Chemo+RT included 2 cycles of gemcitabine/cisplatin before & after RT. Chemo alone included gem/cis x 4. Primary & secondary endpoints were DFS and overall survival (OS). Results: 198 patients were enrolled. 82 (41%) had SqCC & 77 had ≥pT3N0-N+ disease and were analyzed (34 RT, 27 chemo+RT, & 16 chemo). Median age was 53. Median F/U was 20 months (1-127 months). The RT vs chemo arms were well-balanced except for number of nodes removed (mean 12 vs. 9, p=0.05). On univariable analysis, RT was not significantly associated with DFS [HR 0.56 (95%CI 0.26-1.21), p=0.14]. On multivariable analysis, only pN+ was significant. 2-yr DFS was 60% for RT & 43% for chemo (log-rank p=0.13). OS was improved with RT (2-yr OS 71% vs. 43%, p=0.04). There was one death during treatment (chemo-related). There was no significant difference in DFS or OS for RT vs. chemo+RT with 2-yr DFS of 59% & 55% (p=0.65) & 2-yr OS of 67% & 74% (p=0.16). Conclusions: On post-hoc analysis, RT for locally advanced bladder SqCC was associated with significantly improved OS vs. adjuvant chemo. We hypothesize that the inferior OS with chemo was due to increased toxicity & limited efficacy. There was no difference in outcomes for RT vs. chemo+RT. Adjuvant RT should be a standard option for ≥pT3 SqCC of the bladder after RC. Alternative chemo agents for SqCC should be explored. Clinical trial information: NCT01734798.

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