A Phase I/Ii Trial of Transurethral Surgery Combined With Concurrent Cisplatin, 5-Fluorouracil and Twice Daily Radiation Followed by Selective Bladder Preservation in Operable Patients With Muscle Invading Bladder Cancer

Zietman, Anthony L.; Shipley, William U.; Kaufman, Donald S.; Zehr, E; Heney, N.M.; Althausen, Alex F.; McGovern, Francis J.

doi:10.1016/s0022-5347(01)62379-6

Cited by 71 publications

(16 citation statements)

References 18 publications

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“…In a study by Erlangen and several others, responses were evaluated 4 to 6 weeks post-CRT by restaging TURBT (1-3). Conversely, according to the Massachusetts General Hospital (MGH) and Radiation Therapeutic Oncology Group (RTOG) protocols, response evaluation should be performed much earlier, i.e., after approximately 40 Gy of induction radiation therapy (20-22). In the literature, salvage cystectomy plays an important role in patients with a persistent tumor after CRT.…”

Section: Discussionmentioning

confidence: 99%

Single Institutional Experience of Bladder-Preserving Trimodality Treatment for Muscle-Invasive Bladder Cancer

et al. 2008

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The authors designed this study to determine the clinical effectiveness of trimodality treatment, i.e., transurethral resection of a bladder tumor (TURBT) and concurrent chemoradiotherapy (CRT). Twenty patients with a muscle-invasive bladder cancer were treated by TURBT followed by concurrent cisplatin (75 mg/m 2 day), administered on weeks 1 and 4 of radiotherapy. According to residual tumor status after TURBT, patients were classified into patients with a complete TURBT group and incomplete TURBT group. Response to treatment was evaluated by restaging TURBT at 4 weeks after completing CRT (post-CRT). Fifteen patients (75%) achieved complete remission (CR) at restaging; 10 patients (50%) remained continuously free of tumor recurrence. Disease-specific and overall survivals were 51.1% and 38.6% at 5 yr post-CRT, respectively. Of 16 patients in the complete TURBT group, 14 patients (87.5%) achieved CR, which was significantly different from that observed in the incomplete TURBT group, in which only 1 (25%) of 4 patients achieved CR (p=0.032). Five-year disease-specific and overall survivals were 71.6% and 53.5%, respectively. Ten patients (90.9%) maintained their own bladder among the 11 surviving patients. Trimodality treatment was found to be an effective treatment in patients who underwent complete TURBT for a muscle-invasive bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Single Institutional Experience of Bladder-Preserving Trimodality Treatment for Muscle-Invasive Bladder Cancer

et al. 2008

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“…However, the lack of local control of the disease as well as the significant toxicity that is associated with radiation therapy remains problematic [4]–[6]. To improve efficacy, several clinical trials on organ-sparing management were carried out to test the effects of combined chemotherapy and radiation [7], [8]. However despite numerous efforts, chemoradiation studies remain associated with suboptimal local control of disease and decrease survival compared with radical surgery.…”

Section: Introductionmentioning

confidence: 99%

Combining mTOR Inhibition with Radiation Improves Antitumor Activity in Bladder Cancer Cells In Vitro and In Vivo: A Novel Strategy for Treatment

et al. 2013

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PurposeRadiation therapy for invasive bladder cancer allows for organ preservation but toxicity and local control remain problematic. As such, improving efficacy of treatment requires radiosensitization of tumor cells. The aim of study is to investigate if the mammalian Target of Rapamycin (mTOR), a downstream kinase of the phosphatidylinositol 3-kinase (PI3K)/AKT survival pathway, may be a target for radiation sensitization.Experimental DesignClonogenic assays were performed using 6 bladder cancer cell lines (UM-UC3, UM-UC5, UM-UC6, KU7, 253J-BV, and 253-JP) in order to examine the effects of ionizing radiation (IR) alone and in combination with RAD001, an mTOR inhibitor. Cell cycle analysis was performed using flow cytometry. In vivo, athymic mice were subcutaneously injected with 2 bladder cancer cell lines. Treatment response with RAD001 (1.5 mg/kg, daily), fractionated IR (total 9Gy = 3Gy×3), and combination of RAD001 and IR was followed over 4 weeks. Tumor weight was measured at experimental endpoint.ResultsClonogenic assays revealed that in all bladder cell lines tested, an additive effect was observed in the combined treatment when compared to either treatment alone. Our data indicates that this effect is due to arrest in both G1 and G2 phases of cell cycle when treatments are combined. Furthermore, our data show that this arrest is primarily regulated by changes in levels of cyclin D1, p27 and p21 following treatments. In vivo, a significant decrease in tumor weight was observed in the combined treatment compared to either treatment alone or control.ConclusionsAltering cell cycle by inhibiting the mTOR signaling pathway in combination with radiation have favorable outcomes and is a promising therapeutic modality for bladder cancer.

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“…23 However, a promising survival outcome, 56%-73% overall survival rate at 5 years, was reported in several phase II trials. 19,20,24 Chemoradiotherapy with cisplatin monotherapy has shown good tolerance in several reports. 11,18,25 Our study showed that carboplatin alone with radiotherapy provided excellent disease control and was well tolerated in frail or aged patients with bladder cancer.…”

Section: Yin-hsun Feng Et Almentioning

confidence: 99%

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer

Feng

Shen

Huang

et al. 2016

Clinical Genitourinary Cancer

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A Phase I/Ii Trial of Transurethral Surgery Combined With Concurrent Cisplatin, 5-Fluorouracil and Twice Daily Radiation Followed by Selective Bladder Preservation in Operable Patients With Muscle Invading Bladder Cancer

Cited by 71 publications

References 18 publications

Single Institutional Experience of Bladder-Preserving Trimodality Treatment for Muscle-Invasive Bladder Cancer

Single Institutional Experience of Bladder-Preserving Trimodality Treatment for Muscle-Invasive Bladder Cancer

Combining mTOR Inhibition with Radiation Improves Antitumor Activity in Bladder Cancer Cells In Vitro and In Vivo: A Novel Strategy for Treatment

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer

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