Selective bladder preservation with twice-daily radiation plus 5-flourouracil/cisplatin (FCT) or daily radiation plus gemcitabine (GD) for patients with muscle invasive bladder cancer: Primary results of NRG/RTOG 0712—A randomized phase 2 multicenter trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 408-408
Author(s):  
John J Coen ◽  
Peixin Zhang ◽  
Philip James Saylor ◽  
Cheryl T. Lee ◽  
Chin-Lee Wu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Distant Metastasis ◽  
Complete Response ◽  
Multicenter Trial ◽  
Bladder Preservation ◽  
Significance Level ◽  
Gu Toxicity ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Bladder Sparing

408 Background: To assess GD or FCT as the chemoradiation (CRT) component of a bladder sparing regimen. Methods: Patients with T2-4a bladder cancer were randomized. Patients had a maximal transurethral resection and induction CRT to 40 Gy followed by cystoscopic assessment. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others were offered cystectomy and no further CRT. Adjuvant gemcitabine/cisplatin chemotherapy was subsequently administered. The primary endpoint was the rate of distant metastasis at 3 years (DM3). Toxicity and other efficacy related endpoints including CR and bladder intact distant metastasis free survival at 3 years (BI-DMFS3) were also assessed. Using the Clopper-Pearson method, the study required 32 patients per arm, with a benchmark DM3 of 25% and a 1-sided significance level of 0.1. If both arms meet this benchmark, toxicity will be used to select a regimen for future study. This study was not designed to compare arms. Results: From 12/2008 to 4/2014, 70 patients were enrolled; 66 were eligible for analysis (33 per arm). Median follow-up was 4.3 years. DM3 was 22% and 16% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. CR rates were 88% and 78%, respectively. Of 33 patients in the FCT group, 32 (97%) completed induction, 27 (93%) completed induction and consolidation, and 18 (55%) completed the entire protocol. Of 33 patients in the GD group, these figures were 31 (94%), 23 (92%), and 16 (49%), respectively. Of 33 patients in the FCT group, 21 (64%) had grade 3-4 toxicity during protocol treatment with 18 (55%), 2 (6%) and 2 (6%) experiencing hematologic, GI and GU toxicity, respectively. For 33 patients in the GD group, these figures were 18 (55%) overall and 14 (43%), 3 (9%) and 2 (6%), respectively. Conclusions: Both regimens are promising, given DM3 rates < 25%. As there was less toxicity in the GD arm, it would be reasonable to consider a gemcitabine based option as well as a cisplatin based regimen for future trials. Daily radiation may be as effective as twice-daily radiation, which may broaden appeal. Clinical trial information: NCT00777491.

scholarly journals Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712—A Randomized Phase II Trial

2019 ◽  
Vol 37 (1) ◽  
pp. 44-51 ◽  
Author(s):  
John J. Coen ◽  
Peixin Zhang ◽  
Philip J. Saylor ◽  
Cheryl T. Lee ◽  
Chin-Lee Wu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Distant Metastasis ◽  
Complete Response ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Once Daily ◽  
Genitourinary Toxicity ◽  
Grade 3 ◽  
Muscle Invasive

Purpose Fluorouracil plus cisplatin and radiation twice a day (FCT) is an established chemoradiation (CRT) regimen for selective bladder-sparing treatment of muscle-invasive bladder cancer. Gemcitabine and once daily radiation (GD) is a well-supported alternative. The current trial evaluates these regimens. Methods Patients with cT2-4a muscle-invasive bladder cancer were randomly assigned to FCT or GD. Patients underwent transurethral resection and induction CRT to 40 Gy. Patients who achieved a complete response (CR) received consolidation CRT to 64 Gy and others underwent cystectomy. We administered adjuvant gemcitabine/cisplatin chemotherapy. The primary end point was the rate of freedom from distant metastasis at 3 years (DMF3). The trial was not statistically powered to compare regimens, but to assess whether either regimen exceeded a DMF3 benchmark of 75%. Toxicity and efficacy end points, including CR and bladder-intact distant metastasis free survival at 3 years (BI-DMFS3), were assessed. Results From December 2008 to April 2014, 70 patients were enrolled, of which 66 were eligible for analysis, 33 per arm. Median follow-up was 5.1 years (range, 0.4 to 7.8 years) for eligible living patients. DMF3 was 78% and 84% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. Postinduction CR rates were 88% and 78%, respectively. Of 33 patients in the FCT arm, 21 (64%) experienced treatment-related grade 3 and 4 toxicities during protocol treatment, with 18 (55%), two (6%), and two patients (6%) experiencing grade 3 and 4 hematologic, GI, and genitourinary toxicity, respectively. For the 33 patients in the GD arm, these figures were 18 (55%) overall and 14 (42%), three (9%) and two patients (6%), respectively. Conclusion Both regimens demonstrated DMF3 greater than 75%. There were fewer toxicities observed in the GD arm. Either gemcitabine and once daily radiation or a cisplatin-based regimen could serve as a base for future trials of systemic therapy.

Concomitant radical non-platinum radiochemotherapy for elderly patients with invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16135-e16135
Author(s):  
A. Rodica Maricela ◽  
L. N. Minea ◽  
X. Bacinschi ◽  
I. Isacu ◽  
A. Tarlea
Keyword(s):  
Bladder Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Locally Advanced ◽  
Conformal Radiotherapy ◽  
Distant Metastases ◽  
Complete Response ◽  
Bladder Preservation ◽  
Cardiovascular Comorbidities ◽  
Grade 3

e16135 Background: Treatment of bladder cancer in elderly patients is a challenging problem because surgery is often not tolerable and the combination of extensive radiotherapy with chemotherapy is also difficult because of patients’ compliance and associated comorbidities. Our study evaluated concurrent radiochemotherapy in elderly patients with locally advanced bladder cancer (T2-T4) in terms of efficacy and tolerability. Methods: Between January 2005 and December 2007, we treated 34 patients with transitional carcinoma of the bladder, with or without nodal involvement, no distant metastases, and median age 79 years (range 66 - 89 years). Their performance status was 0–1-2 in 10–16–8 patients respectively. Cardiovascular comorbidities were the most common (15 patients). The treatment consisted in conformal radiotherapy (mean irradiation dose = 56.4 Gy) concomitant with biweekly Gemcitabine 200 mg/sqm starting on day 1 of radiotherapy. Results: Response was assessed at 4–6 weeks after the end of treatment by cystoscopy with biopsies and MRI. All the patients could end the intended radiation therapy but four of them could not tolerate all the chemotherapy. 13 patients achieved complete response, 12 patients - partial response and 9 patients stable disease. The most common toxicities were: diarrhea (grade 1–2 in 11 patients, grade 3–6 patients), cystitis (grade 1–2 in 5 patients), leucopenia (grade 1–2 in 12 patients, grade 3–4 in 2 patients), thrombocytopenia (grade 1–2 in 6 patients) and anemia (grade 1–2 in 4 patients). Three patient required hospitalization for dehydration and two for febrile neutropenia. After a median follow-up time of 17.4 months, there were 7 relapses and 5 distant metastases. One-year survival rate was 82.41% (28 patients). 6 patients died, 3 from their cancer and 3 from comorbidities. Conclusions: Chemoradiation is well enough tolerated even in elderly patients and also an efficient and organ sparing therapeutic alternative for patients over 65 years old. The treatment choice was based on patients’ preference considering better quality of life with bladder preservation. The use of age-specific therapy adjustments has shown that aggressive treatment for bladder cancer is associated with improved survival even in elderly patients. No significant financial relationships to disclose.

Neoadjuvant accelerated MVAC (AMVAC) in patients with muscle invasive bladder cancer: Results of a multicenter phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4526-4526 ◽  
Author(s):  
Elizabeth R. Plimack ◽  
Jean H. Hoffman-Censits ◽  
Rosalia Viterbo ◽  
Richard Evan Greenberg ◽  
David Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Invasive Disease ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Intent To Treat

4526 Background: Standard methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) demonstrates a survival benefit in the neoadjuvant setting for patients (pts) with muscle invasive bladder cancer (MIBC). Compared with standard MVAC, AMVAC yielded higher response rates with less toxicity in the metastatic setting. Methods: Pts with MIBC, cT2-T4a, and N0-N1 with CrCl >=50 and adequate hepatic and marrow function were eligible. Pts received 3 cycles of AMVAC (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, cisplatin 70mg/m2) on day 1, with pegfilgrastim 6 mg day 2 or 3, every 2 weeks. Pts with CrCl < 60 could receive cisplatin split over 2 days. Radical cystectomy (RC) with lymph node dissection was performed 4-8 weeks after the last dose of chemotherapy. Primary endpoint was pathologic complete response (pCR) rate. Results: Accrual is complete with 44 MIBC pts enrolled at 2 institutions (FCCC, TJU) over a 25 month period. Median age 64 (range 45-83). Three withdrew from study early and are not evaluable for response (2 physician discretion, 1 withdrawal of consent). An additional 8 are currently receiving treatment on study with toxicity and response data pending. Of the 33 evaluable pts for whom final data is available, 30 received all 3 cycles of AMVAC at full dose. Three pts received < 3 cycles due to grade 3 fatigue (1), low platelets (1), and disease progression precluding RC (1). 32/33 pts underwent RC, all within 8 weeks of last chemotherapy. Median time from start of chemotherapy to RC was 9.7 wks (range 4.6-13 wks). 13/33 pts (39.4%, 95% CI, 22.7-56.1%) had a pCR. An additional 3 (9.1%) were downstaged to non muscle invasive disease. For the intent to treat cohort (n=36) 8 pts had grade 3-4 AMVAC related adverse events, the most common being anemia (3), fatigue (3) and neutropenia (2) and overall pCR rate was 36.1%. (95% CI, 20.4-51.8%). All pts will have completed study treatment by April 2012. Final results will be presented. Conclusions: Neoadjuvant AMVAC is well tolerated and preliminary results show a pCR rate similar to that reported for standard 12-week MVAC, suggesting that AMVAC for three cycles (6 weeks) is a safe and efficient alternative.

External beam radiotherapy and concurrent gemcitabine for muscle-invasive bladder cancer: Toxicities and early outcomes.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 443-443 ◽  
Author(s):  
Elana Nack ◽  
Jonathan E. Rosenberg ◽  
Bernard H. Bochner ◽  
Guido Dalbagni ◽  
Michael J. Zelefsky ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
External Beam Radiotherapy ◽  
Survival Outcomes ◽  
External Beam ◽  
Muscle Invasive Bladder Cancer ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Disease Specific

443 Background: To report toxicities and early outcomes of external beam radiotherapy (EBRT) with concurrent gemcitabine for muscle-invasive bladder cancer (MIBC) Methods: Between 9/04 - 4/15, 85 patients (median age 77) with MIBC (cT2-T4, Nx-3) underwent transurethral resection (TUR) (39 complete, 43 incomplete, 2 unknown) followed by EBRT (median dose 64.8Gy) with concurrent gemcitabine (20-27 mg/m2) twice weekly. 25 patients (29%) received neoadjuvant chemotherapy. Patients were followed q3 months with imaging, cystoscopy and/or cytology. Early ( < 90 days) and late ( > 90 days) toxicities were graded according to the Common Terminology Criteria for Adverse Events (v4.0). Median followup was 19.5 months; 74 (87%) had > 3 month followup. Kaplan-Meier and Cox regression were used for survival and multivariate analyses. Results: Acute grade ≥ 3 hematologic, gastrointestinal or genitourinary toxicity occurred in 18%, 1.5% and 1.3% of patients, respectively. 73/85 (86%) patients received full EBRT course without interruption. 78/85 (92%) received > 50% of the prescribed gemcitabine. The most common reason for a gemcitabine interruption/dose reduction was hematologic (80%). Late grade 3 toxicity included hematuria (n = 5), urinary obstruction (n = 4) and cystitis (n = 1). The 2-year freedom from in-bladder recurrence and bladder-intact survival was 53% and 60%, respectively. The 2-year distant metastasis-free, disease-specific and overall survivals were 66%, 69% and 62%, respectively. A complete TUR was associated with improvements in 2 year bladder-intact (73% vs 51%, p = 0.01), disease-specific (87% vs 54%, p = 0.001), distant metastasis-free (83% vs 52%, p < 0.0001) and overall survival (78% vs 50%, p = 0.003) compared with incomplete TUR. Neoadjuvant chemotherapy and nodal status had no significant impact on survival outcomes. Conclusions: EBRT with concurrent gemcitabine is well-tolerated for MIBC, even in an elderly population. Hematologic (acute) and genitourinary (late) toxicities are most common. Survival outcomes in this unselected population are comparable to prior trials, although longer followup is needed. A complete TUR prior to chemoradiation is strongly recommended.

Phase 2 trial of gemcitabine, cisplatin, plus nivolumab with selective bladder sparing in patients with muscle- invasive bladder cancer (MIBC): HCRN GU 16-257.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4503-4503
Author(s):  
Matt D. Galsky ◽  
Siamak Daneshmand ◽  
Kevin G. Chan ◽  
Tanya B. Dorff ◽  
Jeremy Paul Cetnar ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Complete Response ◽  
Normal Cytology ◽  
Entire Cohort ◽  
Phase 2 Trial ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
The Impact

4503 Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients with MIBC but efforts to advance this paradigm have been complicated by (a) lack of prospective studies exclusively testing cisplatin-based neoadjuvant chemotherapy, (b) lack of rigorous methods to define clinical complete response (cCR) and its association with long term outcomes and (c) limited understanding of the role of “salvage” cystectomy. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder/prostatic urethral biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance; otherwise, patients underwent cystectomy. Coprimary endpoints included (1) cCR rate and (2) ability of cCR to predict 2-year metastasis-free survival (MFS). The key secondary endpoint was the impact of genomic alterations in baseline TURBT (TMB, ERCC2, FANCC, RB1, ATM) on performance of cCR for predicting MFS. The cCR rate coprimary endpoint, and interim analysis of 1-year outcomes, are reported. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%) and 64 (84%) have completed post-cycle 4 restaging; 31/64 achieved a cCR (48%; 95% CI 36%, 61%). The median follow-up of cCR patients is 13.7 months (range, 2.5-24 months). One cCR patient opted for immediate cystectomy (pTaN0M0). Outcomes for the entire cohort are summarized in the table below. Local recurrence has occurred in 8/31 cCR patients and 6 underwent cystectomy (pT0N0 = 1, pTaN0 = 1, pTisN0 =1, pT2N0 = 2, pT4N1 = 1). TMB ≥ 10 mut/Mb (p=0.02) or mutant ERCC2 (p=0.02) were associated with cCR or pT0. Conclusions: TURBT + gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a large subset of patients with MIBC. 1-year bladder intact survival is possible though the durability of responses, and role of genomic biomarkers in management algorithms, requires longer follow-up. Clinical trial information: NCT03558087. [Table: see text]

Intra-Arterial Chemotherapy for Muscle-Invasive Bladder Cancer Following Transurethral Resection

2015 ◽  
Vol 94 (4) ◽  
pp. 406-411 ◽  
Author(s):  
Shengjie Liang ◽  
Qingsong Zou ◽  
Bangmin Han ◽  
Yifeng Jing ◽  
Di Cui ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Clinical Stage ◽  
Complete Response ◽  
Intravesical Instillation ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Muscle Invasive

Purpose: To assess the efficacy of intra-arterial chemotherapy as a bladder-preservation treatment in patients with muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumors (TURBT). Materials and Methods: From 2005 June to 2012 November, 46 patients diagnosed with MIBC (clinical stage T2-T3N0M0) underwent three courses of cisplatin-based intra-arterial chemotherapy as a remedial approach for bladder preservation after TURBT. All patients also received intravesical instillation of chemotherapy as a maintenance strategy. Results: All 46 patients completed the treatment with minor complications. The median follow-up time was 34.5 months (range, 8-87 months). Thirty-two patients (69.6%) demonstrated complete response. The three-year and five-year overall survival was 70.65 and 61.23%, and the disease-specific survival over the same periods was 78.03 and 67.62%, respectively. During the entire follow-up period, more than 80% preserved their bladder. Conclusions: Intra-arterial chemotherapy can be performed as a remedial treatment for MIBC patient following TURBT. Combined with TURBT, it offers an option for bladder preservation therapy on patients who are unable or unwilling to undergo radical cystectomy.

Selective organ preservation with neoadjuvant chemotherapy in the treatment of muscle invasive transitional cell carcinoma (TCC) of the bladder.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 310-310
Author(s):  
Shaista Hafeez ◽  
Robert Anthony Huddart
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Poor Response ◽  
Complete Response ◽  
Radical Radiotherapy ◽  
Bladder Preservation ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

310 Background: Radiotherapy has been previously associated with high treatment failure for those with muscle invasive bladder cancer. Evidence suggests modern organ sparing approaches may have favourable outcome in appropriately selected patients. We investigate whether response to neo-adjuvant chemotherapy can guide selection for bladder preservation and identify those patients likely to have greater success with radical radiotherapy treatment. Methods: Retrospective analysis of 94 patients with T2-T4aN0M0 bladder TCC treated between January 2000 and June 2011. Patients received platinum based chemotherapy following transuretheral resection of bladder tumour, with repeat cystoscopy (+biopsy) performed to guide subsequent management. Poor responders were advised to proceed with surgery. We report on the outcome of 79 individuals who received radiotherapy. Results: 56 (60%) patients achieved complete response following chemotherapy (72% with stage T2). 15 (16%) patients achieved partial pathological response. 12 patients had radiological assessment of partial response made. 11 patients had poor response. All patients achieving complete response, 22 with partial response and 1 with poor response proceeded to radical radiotherapy. Median time to disease progression following radiotherapy was 17months (range 8-91). 5 patients developed invasive recurrence, 17 developed superficial recurrence, 4 developed local nodal disease and 7 developed metastasises. After median follow-up of 36 months (range 6-114), 50 patients were alive with no disease, 24 had died (14 from metastatic bladder cancer and 10 from other causes). 5 patients were alive with active disease (4 with localized and 1 with metastatic disease). 13 required cystectomy (9 for superficial disease, 3 for invasive recurrence, and 1 for treatment related toxicity). Of those alive and disease free 84% had an intact bladder. 82% had an intact bladder at last follow-up or death. Conclusions: Neoadjuvant chemotherapy followed by radical radiotherapy allows bladder preservation in over 80% of selected patients with survival rates comparable to contemporary surgical series.

Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer: SWOG S1605 (NCT #02844816).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5022-5022 ◽  
Author(s):  
Peter C. Black ◽  
Catherine Tangen ◽  
Parminder Singh ◽  
David James McConkey ◽  
Scott Lucia ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Phase Ii ◽  
Complete Response ◽  
Median Number ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Bcg Therapy ◽  
Muscle Invasive

5022 Background: Radical cystectomy (RC) is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC), but many patients are unfit for surgery or elect bladder preservation. Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 in NMIBC after BCG therapy, this trial was designed to evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This single arm phase II registration trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year aimed to enroll 135 (70 CIS and 65 non-CIS) eligible patients with histologically proven BCG-unresponsive high risk NMIBC who were unfit for or declined RC. Here we report on the subset with CIS (with or without concomitant Ta/T1) among patients who received at least one protocol treatment. The primary endpoint was pathological complete response (CR) rate at 6 months as defined by mandatory biopsy with a null hypothesis of 30% and alternative of 50% with a 1-sided alpha = 0.05 and 96% power. The 3 month CR rate, defined by cytology, cystoscopy and for-cause biopsy, is reported here as a secondary endpoint, in addition to safety. Results: Seventy-five eligible CIS patients were enrolled. Two received no treatment and are not evaluable. Of 73, median patient age was 73.4 years and median number of prior BCG doses was 12. Concomitant Ta/T1 tumor was found in 30 (41.1%) patients, including T1 disease in 16 (21.9%). A CR was observed in 30 (41.1%; 95% CI 29.7%, 53.2%) patients at 3 months and 19 (26.0%; 95% CI 16.5%, 37.6%) at 6 months. Any possibly or probably treatment-related adverse event (AE) was observed in 61 (83.6%) patients. The most frequent AEs were fatigue 36 (49.3%), pruritis 8 (11.0%), hypothyroidism 8 (11.0%), and nausea 8 (11.0%). Grade 3-5 AEs occurred in 9 (12.3%) patients and there was one treatment-related death (myasthenia gravis with respiratory failure and sepsis). Conclusion: The observed response to atezolizumab at 3 and 6 months in patients with BCG-unresponsive CIS was similar to that reported in recent similar trials and meets the benchmark for initial CR defined by the FDA guidance. This trial provided no new safety concerns. The duration of response will determine if this is a suitable treatment option for patients with BCG-unresponsive high risk CIS. Clinical trial information: 02844816 .

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