title: Combined treatment of invasive bladder carcinoma with transurethral resection, induction chemotherapy, and radical radiotherapy plus concomitant protracted infusion of cisplatin and 5-fluorouracil: a phase I study.
abstract: BACKGROUND
  The aim of this study was to define the maximum tolerated doses (MTDs) of cisplatin (CDDP) and 5-fluorouracil (5-FU) administered as protracted intravenous infusion (PVI) during hyperfractionated radiotherapy (HFRT) administered with organ-sparing intent to patients with infiltrating transitional cell carcinoma of the bladder (TCCB).
  
  
  METHODS
  Twenty-five patients with T2-T4aNXM0 TCCB were enrolled in this study. After a complete transurethral resection, bladder mapping, and two cycles of induction chemotherapy, patients were submitted to HFRT and CDDP + 5-FU as concomitant PVI at escalating dose levels until MTDs were reached. Treatment efficacy was also evaluated, in terms of complete response (CR) rates and cystectomy free, disease free, and overall survival.
  
  
  RESULTS
  Combined treatment was well tolerated. The recommended doses for Phase II studies of PVI chemotherapy and radiotherapy for patients with invasive bladder carcinoma are CDDP 5 mg/m2/day and 5-FU 220 mg/m2/day. Twenty-four patients were evaluable for response: 21 (87.5%) had CR and 3 PR. After a median follow-up of 31 months (range, 11-49 months), 18 of 21 patients with CRs (86%) were alive: 15 (71.4%) had tumor free bladder, of whom 3 had superficial recurrence successfully treated with endovesical therapy and 1 had distant metastases. Three patients were submitted to cystectomy, one for superficial recurrence and hematuria and two for invasive bladder recurrence.
  
  
  CONCLUSIONS
  This study defines the MTDs of CDDP and 5-FU concomitantly administered with hyperfractionated radiotherapy. The low toxicity observed and the high CRs and bladder preservation rates deserve further study.
authors.affiliation: Environmental Department, ENEA Casaccia, Rome, Italy.
authors.forename: D T
authors.initials: DT
authors.lastname: Danesi
authors.forename: G
authors.initials: G
authors.lastname: Arcangeli
authors.forename: E
authors.initials: E
authors.lastname: Cruciani
authors.forename: A
authors.initials: A
authors.lastname: Mecozzi
authors.forename: B
authors.initials: B
authors.lastname: Saracino
authors.forename: S
authors.initials: S
authors.lastname: Giacobini
authors.forename: E
authors.initials: E
authors.lastname: Pannunzio
authors.forename: A
authors.initials: A
authors.lastname: Biggio
authors.forename: F
authors.initials: F
authors.lastname: Orefici
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012074:Remission Induction; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate