title: Phase II trial of dose-dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function.
abstract: BACKGROUND
  Cisplatin-based therapy is standard in patients with advanced urothelial carcinoma but a large proportion are ineligible due to renal impairment. The safety and activity of a dose-dense carboplatin-based regimen in this patient population were explored.
  
  
  METHODS
  Patients with advanced urothelial carcinoma who were ineligible for cisplatin were eligible based on at least 1 of the following: 1) serum creatinine >1.5 mg/dL; 2) creatinine clearance of >30 mL/min/1.73 m(2) and <60 mL/min/1.73 m(2); and/or 3) prior nephrectomy. Patients received treatment with doxorubicin plus gemcitabine every other week x 5 cycles followed by paclitaxel plus carboplatin weekly x 12 cycles.
  
  
  RESULTS
  Twenty-five patients were treated. Myelosuppression was the major toxicity, with 28% of patients experiencing grade 3-4 neutropenia; there were only 2 (8%) episodes of febrile neutropenia. Grade > or = 3 nonhematologic toxicities were infrequent with the exception of grade > or = 3 thrombotic episodes in 4 (16%) patients. There were 5 complete responses and 9 partial responses for an overall response rate of 56% (95% confidence interval [CI]: 35%-76%). The median survival was 15 months (95% CI: 11-30). At a median follow-up for survivors of 45 months, 7 (28%) patients are disease-free.
  
  
  CONCLUSIONS
  Dose-dense sequential chemotherapy is tolerable and active in patients with urothelial carcinoma and renal impairment. Prolonged disease-free survival is achievable in a subset of patients with primary unresectable disease or lymph-node only metastases treated with carboplatin-based therapy +/- surgical consolidation. Randomized trials are needed to define the optimal regimen in patients with advanced urothelial carcinoma and renal impairment.
authors.affiliation: Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. matthew.galsky@usoncology.com
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Svetlana
authors.initials: S
authors.lastname: Mironov
authors.forename: Joseph
authors.initials: J
authors.lastname: Scattergood
authors.forename: Mary G
authors.initials: MG
authors.lastname: Boyle
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine