title: Cisplatin, gemcitabine, and ifosfamide as weekly therapy: a feasibility and phase II study of salvage treatment for advanced transitional-cell carcinoma.
abstract: OBJECTIVE
  We investigated the feasibility, safety, and antitumor activity of weekly gemcitabine given in combination with low doses of cisplatin and ifosfamide in previously treated patients with advanced transitional-cell carcinoma (TCC) of the urothelium.
  
  
  METHODS
  Patients with measurable, metastatic or unresectable TCC who had received one or two prior chemotherapy regimens were eligible. On a 28-day course, doses of cisplatin 30 mg/m(2), gemcitabine 800 mg/m(2), and ifosfamide 1 g/m(2) were given on day 1 and then repeated on day 8 and day 15 unless there was dose-limiting hematologic toxicity.
  
  
  RESULTS
  Fifty-one patients were registered; 10 patients participated in a pilot study, after which 41 patients were registered onto the phase II protocol. Forty-eight patients (94.1%) had dose-limiting hematologic toxicity on day 8 or day 15. Nonhematologic toxicity of grade 3 or greater consisted mainly of nausea and vomiting (seven patients, 13.7%) and infection (seven patients, 13.7%). Responses could be assessed in 49 of 51 eligible patients; two complete responses (4.1%) and 18 partial responses (36.7%) were observed for an overall response rate of 40.8% (exact 95% confidence interval, 27% to 56%).
  
  
  CONCLUSIONS
  This regimen of cisplatin, gemcitabine, and ifosfamide is not feasible for weekly administration because of hematologic toxicity. Nevertheless, there was promising activity with only two doses per 28-day cycle. On the basis of these results, we have initiated a phase II trial of this combination given as a single dose every 14 days in patients with untreated, metastatic urothelial carcinoma.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. lpagliar@mdanderson.org
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Tu
authors.forename: Dallas
authors.initials: D
authors.lastname: Williams
authors.forename: Danai
authors.initials: D
authors.lastname: Daliani
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016879:Salvage Therapy; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003841:Deoxycytidine; D002945:Cisplatin; D007069:Ifosfamide; D000093542:Gemcitabine