title: A phase I study of gemcitabine, 5-fluorouracil and leucovorin in patients with advanced, recurrent, and/or metastatic solid tumors.
abstract: BACKGROUND
  This was a dose escalation phase I trial designed to establish the MTD (maximum tolerated dose) and toxicity profile of the combination of gemcitabine, leucovorin and 5-fluorouracil (5-FU).
  
  
  METHODS
  Standard eligibility criteria were required for patients with advanced malignancy to enroll. Gemcitabine was escalated from an initial dose of 800 mg/m2. Gemcitabine was administered prior to leucovorin (25 mg/m2) followed by bolus 5-FU (600 mg/m2) every week for 3 weeks followed by 1 week of rest.
  
  
  RESULTS
  Of 21 patients enrolled, 20 were eligible for MTD determination. Patients received a median of three 4-week cycles of chemotherapy (range: 1 to 8 cycles). Toxicity was predominantly hematologic or gastroenterologic. Four dose levels were studied. At a gemcitabine dose of 1,500 mg/m2 systemic symptoms of fatigue accompanied hematologic toxicity and patients refused further therapy. At 1,250 mg/m2, full dose intensity was not delivered during the first cycle in 7 of 8 patients treated. Therefore, 1,000 mg/m2 was established as the recommended phase II dose for gemcitabine in this study. Antitumor activity was seen at all dose levels.
  
  
  CONCLUSIONS
  The combination of gemcitabine, leucovorin and 5-FU was tolerable at full doses of all 3 drugs with an expected toxicity profile. Recommended phase II dose for gemcitabine was 1,000 mg/m2. Initial evidence of clinical activity was seen in a variety of tumor types.
authors.affiliation: Division of Oncology, University of Wisconsin, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Berlin
authors.forename: D B
authors.initials: DB
authors.lastname: Alberti
authors.forename: R Z
authors.initials: RZ
authors.lastname: Arzoomanian
authors.forename: C A
authors.initials: CA
authors.lastname: Feierabend
authors.forename: K J
authors.initials: KJ
authors.lastname: Simon
authors.forename: K A
authors.initials: KA
authors.lastname: Binger
authors.forename: R M
authors.initials: RM
authors.lastname: Marnocha
authors.forename: G
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D002955:Leucovorin; D005472:Fluorouracil