title: Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292.
abstract: Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.
authors.affiliation: Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, New York 10467, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Sparano
authors.forename: S
authors.initials: S
authors.lastname: Lipsitz
authors.forename: S
authors.initials: S
authors.lastname: Wadler
authors.forename: R
authors.initials: R
authors.lastname: Hansen
authors.forename: P W
authors.initials: PW
authors.lastname: Bushunow
authors.forename: J
authors.initials: J
authors.lastname: Kirkwood
authors.forename: P J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: J P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: A B
authors.initials: AB
authors.lastname: Benson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; 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*; D001219:Aspartate Aminotransferases / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D005472:Fluorouracil