title: Combined chemoradiation therapy with twice-weekly gemcitabine and cisplatin for organ preservation in muscle-invasive bladder cancer: long-term results of a phase 1 trial.
abstract: OBJECTIVE
  Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting.
  
  
  METHODS
  Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control.
  
  
  RESULTS
  Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months.
  
  
  CONCLUSIONS
  This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.
authors.affiliation: Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier, France; INSERM, U896, IRCM, Montpellier, France. Electronic address: david.azria@icm.unicancer.fr.
authors.forename: David
authors.initials: D
authors.lastname: Azria
authors.affiliation: Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Riou
authors.affiliation: Department of Urology, Clinique Beausoleil, Montpellier, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Rebillard
authors.affiliation: Biostatistics Unit, Montpellier Cancer Institute, Montpellier, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Thezenas
authors.affiliation: Department of Urology, Montpellier University Hospital, Montpellier, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thuret
authors.affiliation: Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Fenoglietto
authors.affiliation: Department of Medical Oncology, AP-HP Saint-Louis, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Pouessel
authors.affiliation: Department of Medical Oncology, AP-HP Saint-Louis, Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Culine
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D059351:Organ Sparing Treatments / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D015996:Survival Rate; D001743:Urinary Bladder / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine