title: A phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  We reported previously that the combination of gemcitabine and continuous infusion fluorouracil (5-FU) has activity in renal cell carcinoma. Based upon in vitro synergy of gemcitabine/cisplatin and 5-FU/cisplatin, we hypothesized that the addition of cisplatin could improve the objective response rate of gemcitabine and 5-FU with manageable toxicity.
  
  
  METHODS
  Twenty-one patients with metastatic renal cell carcinoma (RCC) and a Cancer and Leukemia Group B performance status of 0 to 2 were enrolled. Ten had received prior systemic therapy. Treatment consisted of gemcitabine 600 mg/m2 and cisplatin 20 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Continuous infusion 5-FU was given from day 1 to day 21.
  
  
  RESULTS
  No complete responses and one partial response were observed for an objective response rate of 5% (95% confidence interval 0% to 24%). Two minor responses (25% to 50% regression) were also observed. The median overall survival was 10 months with 35% of patients surviving at 1 year. Grade 3-4 myelosuppression (mostly thrombocytopenia) occurred in nine (43%) patients. Nausea/vomiting and neuropathy were dose-limiting in an additional five patients. Only 51% of treatment cycles were delivered on time and without dose reduction.
  
  
  CONCLUSIONS
  The addition of cisplatin to gemcitabine and 5-FU did not improve the objective response rate of gemcitabine and 5-FU alone and added to the toxicity. Due to the cumulative toxicity, further trials with this cisplatin-containing regimen in RCC are not indicated.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, IL 60637-1470, USA. cgeorge@medicine.bsd.uchicago.edu
authors.forename: C M
authors.initials: CM
authors.lastname: George
authors.forename: N J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: B I
authors.initials: BI
authors.lastname: Rini
authors.forename: F J
authors.initials: FJ
authors.lastname: Geoffroy
authors.forename: P
authors.initials: P
authors.lastname: Kollipara
authors.forename: W M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine