title: Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: a phase I trial.
abstract: BACKGROUND
  We conducted a phase I trial of gemcitabine (gem) with concurrent radiotherapy in patients with muscle-invasive bladder cancer (BC) ineligible for surgery or cisplatin or refusing organ loss.
  
  
  METHODS
  Patients with urothelial cancer, cT2-T4, cN0-1, M0, ineligible for surgery due to local tumor extension, PS, age or co-morbidities or who refused surgery were included. After maximal transurethral resection, the treatment schedule included: twice-weekly i.v. infusion of gem [dose levels (DL) 1-6: 20, 27, 30, 33, 50 and 40 mg/m(2), respectively] for 30 min and concurrent radiotherapy (RT) to the bladder with 55.5 Gy. The primary end point was to determine the maximum-tolerated dose (MTD) and the dose recommended (RD) for further studies of this gem schedule. The secondary end point was late toxicity. The MTD was defined by dose-limiting toxicity (DLT) in 2 or more of 6 patients, discontinuation of RT and/or gem for >1 week in 2 or more of 6 patients due to grade (G) 3/4 acute and/or late toxicity in more than 2 of 18 patients.
  
  
  RESULTS
  Thirty-five of 44 patients were assessable for toxicity and thus the primary end point. DLTs occurred in two of five patients at dose level 5: one G3 alanine aminotransferase elevation and one G3 fatigue. The MTD, therefore, was 50 mg/m(2) gem twice weekly. At DL 6 with 40 mg/m(2), the RD was established: only one of six patients developed G3 fatigue and diarrhea. Late toxicity was rare and of low grade (only G1-2). The 2-year locoregional failure rate was 32% (9/28); 10 of 28 patients (38%) were alive with an intact bladder and no evidence of recurrent disease, 9 patients developed distant metastases and 6 died of their disease.
  
  
  CONCLUSIONS
  Gemcitabine in combination with RT is well tolerated in BC patients ineligible for surgery and/or cisplatin. The RD of gemcitabine for subsequent trials is 40 mg/m(2) twice weekly with concurrent radiation.
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB Cluster Translational Oncology (LB-CTO), Kaiser Franz Josef-Spital, Vienna; Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna)/CEADDP, Vienna. Electronic address: maria.desantis@wienkav.at.
authors.forename: M
authors.initials: M
authors.lastname: De Santis
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB Cluster Translational Oncology (LB-CTO), Kaiser Franz Josef-Spital, Vienna; Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna)/CEADDP, Vienna.
authors.forename: M
authors.initials: M
authors.lastname: Bachner
authors.affiliation: Institute for Radiooncology, KFJ-Hospital, Vienna.
authors.forename: M
authors.initials: M
authors.lastname: Cerveny
authors.affiliation: Department for Radiotherapy and Radio-Oncology, Landeskrankenhaus Salzburg, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Kametriser
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB Cluster Translational Oncology (LB-CTO), Kaiser Franz Josef-Spital, Vienna; Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna)/CEADDP, Vienna.
authors.forename: T
authors.initials: T
authors.lastname: Steininger
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB Cluster Translational Oncology (LB-CTO), Kaiser Franz Josef-Spital, Vienna; Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna)/CEADDP, Vienna.
authors.forename: R
authors.initials: R
authors.lastname: Königsberg
authors.affiliation: Institute for Radiooncology, KFJ-Hospital, Vienna.
authors.forename: A
authors.initials: A
authors.lastname: Schratter-Sehn
authors.affiliation: Department for Radiotherapy and Radio-Oncology, Landeskrankenhaus Salzburg, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Sedlmayer
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB Cluster Translational Oncology (LB-CTO), Kaiser Franz Josef-Spital, Vienna; Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna)/CEADDP, Vienna.
authors.forename: C
authors.initials: C
authors.lastname: Dittrich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000410:Alanine Transaminase; D000093542:Gemcitabine
keywords: bladder cancer; gemcitabine; inoperable; radiosensitizer; radiotherapy; urothelial