title: Combined-modality therapy with gemcitabine and radiotherapy as a bladder preservation strategy: results of a phase I trial.
abstract: OBJECTIVE
  We conducted a phase I trial of gemcitabine given twice weekly with concurrent radiotherapy in patients with muscle-invasive bladder cancer.
  
  
  METHODS
  Eligible patients underwent maximal transurethral resection of their bladder tumors followed by twice-weekly infusion of gemcitabine with 2 Gy/d concurrent radiotherapy to the bladder, for a total of 60 Gy over 6 weeks. The starting dose of gemcitabine was 10 mg/m(2) with subsequent dose levels of 20, 27, 30, and 33 mg/m(2). The primary end point was the determination of the maximum-tolerated dose (MTD) of twice weekly gemcitabine with concurrent radiotherapy. Secondary end points included assessment of toxicity associated with combined-modality therapy and initial assessment of the rate of bladder preservation.
  
  
  RESULTS
  Twenty-four patients were enrolled and 23 were assessable for toxicity and response. No significant toxicity was demonstrated at the 10 or 20 mg/m(2) twice-weekly doses. Dose-limiting toxicity (DLT) occurred in two of three patients treated at 33 mg/m(2). Intermediate dose levels of 27 and 30 mg/m(2) were then evaluated. The MTD of gemcitabine was 27 mg/m(2). The DLT was systemic, manifested as an elevation in liver function tests, malaise, and edema. Fifteen of 23 patients (65%) are alive with bladders intact and no evidence of recurrent disease at a median follow-up of 43 months.
  
  
  CONCLUSIONS
  Twice-weekly gemcitabine with concurrent radiotherapy at 2 Gy/d to a total dose of 60 Gy is well-tolerated. The MTD of gemcitabine is 27 mg/m(2). There is a high rate of bladder preservation in this selected group of patients.
authors.affiliation: Department of Internal Medicine, University of Michigan School of Medicine and Comprehensive Cancer Center, AnnArbor, 48109, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kent
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
authors.forename: James
authors.initials: J
authors.lastname: Montie
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lee
authors.forename: Joseph
authors.initials: J
authors.lastname: Herman
authors.forename: Peg
authors.initials: P
authors.lastname: Esper
authors.forename: Judith
authors.initials: J
authors.lastname: Fardig
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine