title: Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with bladder cancer: a Phase II trial.
abstract: BACKGROUND
  Gemcitabine is an active agent in the treatment of bladder cancer. The enzyme deoxycytidine kinase catalyzes the phosphorylation of gemcitabine into the active gemcitabine triphosphate. After an infusion during 30 minutes, this enzyme will be saturated, therefore, accumulation of higher intracellular concentrations of the active gemcitabine triphosphate could be achieved by prolonging the infusion time of gemcitabine.
  
  
  METHODS
  Based on previously published Phase I trials, the efficacy and safety of a combination of cisplatin and gemcitabine given as prolonged infusion were tried in a Phase II study of 57 untreated patients with stage III/IV bladder cancer, which is the most common malignant tumor among Egyptian males. Patients received gemcitabine (250 mg/m(2) during 6-hour infusion) on days 1 and 8, and cisplatin (70 mg/m(2)) on day 2 every 21-day cycle.
  
  
  RESULTS
  The 41 males and 16 females had a median age of 55 years (range 37-77). A total of 37 patients had transitional cell, 15 had squamous cell, 2 had adenocarcinoma, and 3 had undifferentiated cell carcinoma. The median number of cycles given to these 57 patients was 4 (range 1-6). Of 54 evaluable patients, 5 (9.4%) had complete remission, and 27 (50%) partial remission, for an overall response rate of 59.4%. These results are comparable to those of a previous Phase II study of the same combination but with gemcitabine given in the standard dose and schedule. Responses were observed at all disease sites. Both hematologic and nonhematologic toxicity were treatable and not severe.
  
  
  CONCLUSIONS
  Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer. Toxicity, especially myelosuppression, is surprisingly mild. This combination deserves to be tried in other different disease categories.
authors.affiliation: Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt. khaled@internetegypt.com
authors.forename: Hussein
authors.initials: H
authors.lastname: Khaled
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Emara
authors.forename: Rabab M
authors.initials: RM
authors.lastname: Gaafar
authors.forename: Osman
authors.initials: O
authors.lastname: Mansour
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel Warith
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Zaghloul
authors.forename: Osama
authors.initials: O
authors.lastname: El Malt
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine