title: Amsacrine and cisplatin in poor prognosis patients with metastatic transitional cell carcinoma of the urothelium: a phase-II study.
abstract: OBJECTIVE
  Amsacrine, as a single agent, was reported to be effective in patients with metastatic transitional cell carcinoma of the urinary bladder. Amsacrine is also associated with a lower toxicity than cyclophosphamide, doxorubicin and cisplatin therapy and has similar activity. But amsacrine has been forgotten in clinical studies of transitional cell carcinoma of the urinary bladder. The aim of present study was to investigate the toxicity and efficacy of amsacrine and cisplatin in chemotherapy-naive patients with metastatic transitional cell carcinoma of the urinary bladder.
  
  
  METHODS
  We have treated 54 patients (41 males/13 females) with a median age of 62 (38-72) years. Performance status was 0/2, I/27 II/17 and III/8. The treatment included: amsacrine 85 mg/ m(2), days 1-2, and cisplatin 30 mg/m(2), days 2-5. Cycles were repeated every 4 weeks. We applied 169 cycles (median 3/patient). Of 54 patients, 39 had previous surgery and 12 had previous radiotherapy. Histological tumor grade was I/7, II/27 and III/20.
  
  
  RESULTS
  51 patients were evaluable for response (3 patients refused further treatment during the first cycle): 2 complete remission (4%); 15 partial remission (29%); 23 stable disease (45%), and 11 progressive disease (22%). The response rate was 33% (95% CI 21-46). On an intent-to-treat basis the response was 32% (95% CI 19-44). Durations of complete and partial responses were 14 (range 12-16) and 6.5 (range 3-11) months, respectively. Median survival was 9 (range 3-21) months. All patients were evaluable for toxicity. Grades III-IV toxicity was as follows: anemia 11%; neutropenia 37%, and thrombocytopenia 20%. None of the patients was excluded from the study because of toxicity.
  
  
  CONCLUSIONS
  The combination of amsacrine and cisplatin is a regimen with mild and manageable toxicity. The present regimen seems to be active. Randomized study of the present regimen versus another low-toxicity regimens are necessary, especially for poor prognosis patients including those with a low performance status.
authors.affiliation: Institute of Oncology and Radiology of Serbia, Belgrade, FR Yugoslavia. ipopov@ncrc.ac.yu
authors.forename: I
authors.initials: I
authors.lastname: Popov
authors.forename: S
authors.initials: S
authors.lastname: Jelíc
authors.forename: D
authors.initials: D
authors.lastname: Radosavljevíc
authors.forename: Z
authors.initials: Z
authors.lastname: Nikolíc-Tomasevíc
mesh_terms: D000328:Adult; D000368:Aged; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000677:Amsacrine; D002945:Cisplatin