title: Treatment of advanced adenocarcinomas of the exocrine pancreas and the gallbladder with 5-fluorouracil, high dose levofolinic acid and oral hydroxyurea on a weekly schedule. Results of a multicenter study of the Southern Italy Oncology Group (G.O.I.M.).
abstract: BACKGROUND
  To date there is no established chemotherapeutic treatment for patients with unresectable locally advanced and/or metastatic carcinomas of the exocrine pancreas or the gallbladder. A multicenter Phase II trial has been performed by the Southern Italy Oncology Group with the aim of evaluating the clinical effectiveness and tolerability of weekly 5-fluorouracil (5-FU) in modulation with intravenous (i.v.) high dose levofolinic acid and oral hydroxyurea.
  
  
  METHODS
  A total of 70 patients fulfilling the standard eligibility for a Phase II study were enrolled in the trial. Forty patients had advanced pancreatic adenocarcinoma and 30 had advanced gallbladder carcinoma. The treatment schedule was: levofolinic acid, 100 mg/m2, in 500 mL of normal saline over 2-hour infusion followed by 5-FU, 600 mg/m2 i.v. bolus, and oral hydroxyurea, 1000 mg/m2, for 1 day every week for 6 consecutive weeks followed by 15 days of rest.
  
  
  RESULTS
  Among the 40 patients with pancreatic adenocarcinoma, 5 (12.5%; 95% confidence level [CL], 8.5-16.5%) showed a partial response with a median duration of 5.6+ months, and 13 had stable disease. Twenty-two patients progressed. Median survival was 5.8 months. Among patients with advanced gallbladder carcinoma, 9 of 30 had a partial response (30%; 95% CL, 26-34%) with a median duration of 6.5 months, and 8 (27%) had stabilization of disease. Thirteen patients showed progressive disease. Median overall survival was 8 months. Toxicity was mild, with Grade 1 to 2 leukopenia and gastrointestinal toxicity the most frequent side effects. No chemotherapy-related deaths were observed.
  
  
  CONCLUSIONS
  5-FU in modulation with i.v. levofolinic acid and oral hydroxyurea on a weekly schedule is well tolerated by the vast majority of patients with locally advanced and/or metastatic carcinoma of the pancreas or the gallbladder. Although response rate and overall survival for patients with pancreatic adenocarcinoma are far from acceptable, the 30% overall response rate achieved in patients with advanced gallbladder carcinoma suggests that 5-FU in modulation with levofolinic acid and hydroxyurea is active in this neoplasm. The combination of modulated 5-FU with other antineoplastic drugs seems worthy of clinical testing in further controlled trials.
authors.affiliation: Service of Chemotherapy, Policlinico, University of Palermo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: E
authors.initials: E
authors.lastname: Majello
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: G
authors.initials: G
authors.lastname: Pezzella
authors.forename: S
authors.initials: S
authors.lastname: Giuseppe
authors.forename: F
authors.initials: F
authors.lastname: Giotta
authors.forename: F
authors.initials: F
authors.lastname: Riccardi
authors.forename: S
authors.initials: S
authors.lastname: Fortunato
authors.forename: G
authors.initials: G
authors.lastname: Colucci
authors.forename: N
authors.initials: N
authors.lastname: Gebbia
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000284:Administration, Oral; D000368:Aged; D000931:Antidotes / Q000008:administration & dosage* / Q000009:adverse effects; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D005706:Gallbladder Neoplasms / Q000188:drug therapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007558:Italy; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002955:Leucovorin; D005472:Fluorouracil; D006918:Hydroxyurea