Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in  Muscle-Invasive Bladder Cancer

Choudhury, Ananya; Swindell, Ric; Logue, John P; Elliott, Tony; Livsey, Jacqueline E; Wise, Marcus; Symonds, Paul; Wylie, James; Ramani, Vijay; Sangar, Vijay K; Lyons, Jeanette; Bottomley, I.C.; McCaul, Damian; Clarke, Noel W.; Kiltie, Anne E.; Cowan, Richard A

doi:10.1200/jco.2010.31.5721

Cited by 161 publications

(105 citation statements)

References 36 publications

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“…83 According to a phase II trial from the same group using weekly gemcitabine at 100 mg/m 2 with concurrent conformal radiotherapy at 52.5 Gy, the CR rate was 88% (44/50) and 5-year OS and CSS rates were 65% and 78%, respectively. 85 These results encourage phase III trials. In recent series of trimodality therapy (Table 1), systemic chemotherapy with gemcitabine and cisplatin (GC regimen), which showed equivalent efficacy and less toxicity than the MVAC regimen in metastatic bladder cancer patients, 86 was combined in neoadjuvant 23,25 or adjuvant settings.…”

Section: Intensification Of Concomitant or Adjuvant Chemotherapymentioning

confidence: 92%

Selective bladder preservation with curative intent for muscle‐invasive bladder cancer: A contemporary review

Koga

Kihara

2012

Int J of Urology

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Abbreviations & Acronyms BIS = bladder-intact survival CIS = carcinoma in situ CR = complete response CRT = chemoradiotherapy CSS = cancer-specific survival FU = fluorouracil GasLESS = gasless laparoendoscopic single-port surgery GC = gemcitabine, cisplatin HD = hemodialysis IAC = intra-arterial chemotherapy IMRT = intensity-modulated radiation therapy LCRT = low-dose chemoradiotherapy MCV = methotrexate, cisplatin and vinblastine MIBC = muscle-invasive bladder cancer MRI = magnetic resonance imaging MVAC = methotrexate, vinblastine, adriamycin and cisplatin NA = not available NFkB = nuclear factor kB NMIBC = non-muscle-invasive bladder cancer OS = overall survival PC = partial cystectomy PLND = pelvic lymph node dissection QoL = quality of life RC = radical cystectomy RTOC = Radiation Therapy Oncology Group SPARE = Selective bladder Preservation Against Radical Excision TMDU = Tokyo Medical and Dental University TURBT = transurethral resection of bladder tumors Abstract: Radical cystectomy plus urinary diversion, the reference standard treatment for muscle-invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long-term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder-sparing approaches for muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder-sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (S55-65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50-70% at 5 years), while preserving the native bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include (i) muscle-invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle-invasive bladder cancer site; (ii) potential lack of curative intervention for regional lymph nodes; and (iii) increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high-dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (e.g. 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle-invasive bladder cancer patients with favorable quality of life.

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Section: Intensification Of Concomitant or Adjuvant Chemotherapymentioning

confidence: 92%

Selective bladder preservation with curative intent for muscle‐invasive bladder cancer: A contemporary review

Koga

Kihara

2012

Int J of Urology

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“…Choudhury et al [4] who reported OAS 75% at 3 years, Cheon et al [21] who reported 74% at 2 years and Lin et al [22] who reported 77% at 3 years. However, Donald et al [15] reported OAS at 3 years 83%, that mostly due to more aggressive protocol including adjuvant chemotherapy (cisplatin and 5 FU).…”

Section: Figure 2 Bladder Intact Survivalmentioning

confidence: 99%

“…Trimodality bladder-sparing approaches consisting of transurethral resection (TUR), chemotherapy and radiotherapy (RT) yield overall survival rates comparable with those of radical cystectomy series (50%-70% at 5 years), while preserving the native bladder in 40%-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients [3][4][5] .…”

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confidence: 99%

A feasibility study of transurethral resection followed by radiotherapy combined with concurrent twice-weekly gemcitabine in the treatment of invasive bladder carcinoma

Osama

Shalaby

Aboziada

2013

JST

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Introduction and Aim: Radical cystectomy is the traditional treatment of cancer bladder; however, bladder preservation in selective patients is beneficial. To evaluate the efficacy of transurethral resection plus chemo-radiation in achieving bladder preservation, using conformal radiotherapy and twice weekly Gemcitabine. Patients and Methods:Thirty seven patients with good performance status, and maximum trans-urethral resection received 46GY /23 fractions with twice weekly Gemcitabine 30mg/m 2 . Evaluation was done after 2 weeks by cystoscopy and biopsy from the tumor bed. Patients who had complete response (CR) subjected for phase II 20 GY/10 fractions /2 weeks with twice weekly Gemcitabine 30 mg/m 2 . However, patients who had incomplete response subjected for radical cystectomy.Results: Thirty two (86.4%) patients had CR. The treatment schedule was tolerable and was associated with moderate toxicity that was easily treated. Six patients developed G3 toxicity that required treatment interruption until improvement. After 2 years of follow up, 29 patients achieved good local control with 2 years local recurrence free survival was 79%. The 2 years overall survival and bladder intact survival was 70% and 69% respectively. Conclusions:Tri-modality bladder-sparing approach consists of transurethral resection, chemotherapy twice weekly Gemcitabine and radiotherapy is well tolerated, with high rate of bladder preservation. This approach may be considered as a reasonable alternative to cystectomy in the proper selected patients.

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“…Although there are no prospective randomized trials of concurrent chemoradiation (CRT) versus cystectomy, the Medical Research Council (MRC) trial did show better outcomes with 3 cycles of CMV before radiation therapy or cystectomy (25). A phase II trial evaluating concurrent weekly gemcitabine with radiation in 50 patients with T2-3 disease showed good tolerability and a CR rate of 88%, 3-year cancer-specific survival of 82%, and OS of 75% (38). Bladder-sparing approaches focusing on tumor biology, such as radiation with p53-targeted agents or hypoxiamodifying agents, are under study.…”

Section: Bladder Preservation In Muscle-invasive Diseasementioning

confidence: 99%

New Directions for Biologic Targets in Urothelial Carcinoma

Richter

Sridhar

2012

Molecular Cancer Therapeutics

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Urothelial carcinoma remains an important oncologic problem with significant morbidity and mortality. This article provides an overview of the current status of treatment of urothelial carcinoma, with an update on current trials and recent American Society of Clinical Oncology abstracts. As an alternative to focusing on the metastatic setting, we take a broad look at drug development to date, as it spans from early disease to advanced disease in the context of emerging molecular data. This approach allows us to show that each stage involves key considerations based on emerging evidence regarding molecular biology, stage-specific novel endpoints, and rational patient selection that may help further trial designs in the future. Key issues, such as neoadjuvant versus adjuvant perioperative chemotherapy, approaches to salvage second-line therapy in the metastatic setting, and treatment of elderly and cisplatin-ineligible patients, are discussed. New paradigms in clinical research, including novel endpoints, upfront rational patient selection, biomarkers, and trial design, are also addressed. Mol Cancer Ther; 11(6); 1226-35. Ó2012 AACR.

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Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder Cancer

Abstract: Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.

Cited by 161 publications

References 36 publications

Selective bladder preservation with curative intent for muscle‐invasive bladder cancer: A contemporary review

Selective bladder preservation with curative intent for muscle‐invasive bladder cancer: A contemporary review

A feasibility study of transurethral resection followed by radiotherapy combined with concurrent twice-weekly gemcitabine in the treatment of invasive bladder carcinoma

New Directions for Biologic Targets in Urothelial Carcinoma

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