Radiation Therapy With or Without Carbogen and Niacinamide in Treating Patients With Bladder Cancer

A Multicenter Randomized Trial of Radical Radiotherapy With Carbogen in the Radical Treatment of Locally Advanced Bladder Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as carbogen and niacinamide may make tumor cells more sensitive to radiation therapy. It is not yet known whether radiation therapy is more effective with or without carbogen and niacinamide in treating patients who have bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without carbogen and niacinamide in treating patients who have locally advanced bladder cancer.

OBJECTIVES: Compare the 6-month cystoscopic response in patients with locally advanced transitional cell carcinoma of the bladder treated with radical radiotherapy with or without radiosensitization with carbogen and niacinamide. Compare the local failure-free and overall disease-specific survival of patients treated with these regimens. Compare the treatment-related morbidity, in particular acute and chronic bowel and bladder symptoms, in patients treated with these regimens. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive radical radiotherapy once daily, 5 days a week, for 4-6.4 weeks. Patients also receive oral niacinamide once daily 1.5-2 hours before initiation of each radiotherapy dose and carbogen through a closed breathing system (face mask with a tight air seal or a mouthpiece with nasal clip) once daily beginning 5 minutes before initiation and continuing until completion of each radiotherapy dose. Arm II: Patients receive radiotherapy as in arm I. Quality of life is assessed at baseline; at 4 weeks; at 3, 6, and 12 months; and then annually for 4 years. Patients are followed at 8 and 12 weeks; at 6, 9, and 12 months; and then every 6 months for 4 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 330 patients (165 per treatment arm) will be accrued for this study.

stage I bladder cancer, stage II bladder cancer, stage III bladder cancer, transitional cell carcinoma of the bladder

Quality of life as assessed by FACT-BI scale at baseline, week 4, 3 months, 6 months, 12 months, and yearly thereafter for 5 years

DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the bladder Muscle invasive carcinoma (stage T2 or T3) of any grade OR High-grade (G3) superficial bladder carcinoma (T1) OR Prostatic invasion (T4a) No squamous cell carcinoma or adenocarcinoma of the bladder No locally advanced T4b carcinoma No distant metastasis or enlarged pelvic lymph nodes on CT staging scan of the pelvis PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times normal Renal: Creatinine no greater than 2 times normal Cardiovascular: No ischemic heart disease or peripheral vascular disease requiring diuretics or angiotensin-converting enzyme inhibitors Pulmonary: No concurrent respiratory disease with reduced respiratory drive that would preclude the delivery of 95% oxygen Other: Capable of complying with a closed breathing system delivering carbogen through either a mask or a mouthpiece with nasal clip PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Hoskin PJ, Rojas AM, Saunders MI, Bentzen SM, Motohashi KJ; BCON investigators. Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial. Radiother Oncol. 2009 Apr;91(1):120-5. doi: 10.1016/j.radonc.2008.10.001. Epub 2008 Nov 5.

Choudhury A, Porta N, Hall E, Song YP, Owen R, MacKay R, West CML, Lewis R, Hussain SA, James ND, Huddart R, Hoskin P; BC2001 and BCON investigators. Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials. Lancet Oncol. 2021 Feb;22(2):246-255. doi: 10.1016/S1470-2045(20)30607-0.