A phase I-II study of synchronous chemoradiotherapy for poor prognosis locally advanced bladder cancer.

Background: The management of locally advanced bladder cancerremains controversial with poor local control with radiotherapy alone.Synchronous chemotherapy regimens have yielded encouraging results in otherprimary sites.Patients and methods: Patients with T2–T4a N0/NX M0 bladdercancer were entered into this single centre phase I–II study. Patientsreceived radiotherapy to 55 Gy in 20 fractions over four weeks. Concurrentchemotherapy was given with Mitomycin C 12 mg/m² day 1 and5-fluorouracil 500 mg/m²/24 hours weeks one and four ofradiotherapy for five or seven days on each occasion.Results:Thirty-one patients entered the trial from March 1998 toDecember 1999 (22: 5-day; 9: 7-day schedule). Median age was 68 (range58–79) years, 23 males and 8 females; T2: 9 (29%); T3a: 4(12%); T3b: 9 (29%); T4: 9 (29%); TCC grade 2: 8(26%) and grade 3: 23 (74%); 14 of 31 had hydronephrosis. Tenof thirty-one had a GFR <50 ml/min. Toxicity was mild to moderate with thefive-day schedule. More severe toxicity was seen with the seven-day schedule:five of nine patients failed to complete planned therapy. Pathologicalcomplete response rate at three months was 74% (5-day regimen) and50% (7-day regimen). Overall 12-month survival was 65%.Conclusion:Chemoradiotherapy with the five-day schedule isfeasible with acceptable toxicity in poor prognosis patients. A randomisedtrial is being launched.