title: Phase I trial of gemcitabine (Gemzar), 24 h infusion 5-fluorouracil and folinic acid in patients with inoperable pancreatic cancer.
abstract: Gemcitabine (Gemzar) has a significant impact upon survival and quality of life for patients with pancreatic cancer, compared with 5-fluorouracil (5-FU). This phase I study was initiated to define the recommended dose of 5-FU delivered as a 24 h infusion in combination with gemcitabine (1000 mg/m2) and folinic acid (200 mg/m2) in patients with inoperable pancreatic cancer, treated on an outpatient basis. Drugs were administered weekly for 4 weeks out of 6 weeks. Sixteen chemonaive patients (median age 59 years, range 51-66) were enrolled, 15 had stage IV and one stage III disease. The median Karnofsky performance score (KPS) was 70 (range 60-80). Six patients received 5-FU 750 mg/m2, eight received 5-FU 1000 mg/m2 and two received 5-FU 1250 mg/m2. The maximum tolerated dose of 5-FU was 1000 mg/m2. Hepatotoxicity was dose limiting. One patient who received 5-FU 1250 mg/m2 died as a result of hepatorenal failure. There was one partial response, nine patients had stable disease for more than 3 months and 13 patients had improved KPS. The median time to progressive disease was 31 weeks (range 5-50 weeks). A phase 11 trial is underway to further assess the activity of this combination at the recommended dose of 750 mg/m2 5-FU.
authors.affiliation: Medizinische Klinik und Poliklinik mS Hämatologie und Onkologie, Medizinische Fakultät der Humboldt Universität zu Berlin, Germany. pankreas@charite.de
authors.forename: H
authors.initials: H
authors.lastname: Oettle
authors.forename: U
authors.initials: U
authors.lastname: Pelzer
authors.forename: K
authors.initials: K
authors.lastname: Hochmuth
authors.forename: T
authors.initials: T
authors.lastname: Diebold
authors.forename: J
authors.initials: J
authors.lastname: Langrehr
authors.forename: C A
authors.initials: CA
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Arning
authors.forename: T J
authors.initials: TJ
authors.lastname: Vogl
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
authors.forename: D
authors.initials: D
authors.lastname: Huhn
authors.forename: H
authors.initials: H
authors.lastname: Riess
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine