title: A phase I trial of fixed dose rate gemcitabine and capecitabine in metastatic renal cell carcinoma.
abstract: BACKGROUND
  Metastatic renal cell carcinoma (RCC) has modest response rates to chemotherapy with gemcitabine and 5-fluorouracil (5-FU). Fixed dose rate gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. To determine the toxicity of this combination therapy in metastatic RCC, a Phase I trial was conducted.
  
  
  METHODS
  Patients with metastatic RCC were enrolled in a Phase I dose escalation trial. Patients received fixed dose rate gemcitabine on Days 1, 8, and 15 in combination with capecitabine, an oral 5-FU analog, given on Days 1-21 of a 28-day cycle.
  
  
  RESULTS
  Nine patients were enrolled at one of two dose levels. The initial dose level produced dose-limiting toxicity (DLT), including prominent palmar-plantar erythrodysesthesia (hand-foot syndrome). A modified second dose level also resulted in DLT, precluding further study. No central nervous system (CNS) toxicity was observed in three patients with CNS metastases. Two patients demonstrated an objective partial response.
  
  
  CONCLUSIONS
  Fixed dose rate gemcitabine in combination with capecitabine produced unacceptable toxicity in patients with advanced RCC. Further development of this schedule in RCC cannot be recommended.
authors.affiliation: Department of Hematology/Oncology, The University of California San Francisco Comprehensive Cancer Center, San Francisco, California, USA. brini@medicine.ucsf.edu
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D005533:Foot Dermatoses / Q000139:chemically induced; D006229:Hand Dermatoses / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine