title: A new pharmacological approach to gastrointestinal cancer at high risk of relapse based on maintenance of the cytostatic effect.
abstract: In metastatic colorectal and other locally advanced gastrointestinal cancers, the mechanisms of tumor growth and/or immune escape by residual cancer cells after curative resection often provoke tumor recurrence. Current adjuvant therapy is based on pharmacological administration up to 6-8 months after surgery. We hypothesized that the long-term, cytostatic action from repeated post-adjuvant administration of 5-fluorouracil (FU)-leucovorin (LV) cycles, as a result of the downregulation of the above-mentioned cellular mechanisms, could halt tumor progression. An active prospective cohort, including 19 patients (study group) at high risk of relapse, was considered. All patients received repeated post-adjuvant administration of 5-FU-LV cycles for up to 52-60 months following curative surgery (total cumulative dose of about 90 g and mean follow-up of 70.6 ± 49.7 months). The 5-year disease-free interval (DFS) and overall survival (OS) were 80.4 ± 10.2% and 87.1 ± 8.6%, respectively, which is very different from the recent literature that has reported 5-year DFS and OS values of 31.8% and 40.1%, respectively. These findings suggest that this new pharmacological approach based on the long-term maintenance of a cytostatic effect with 5-FU-LV can produce a relevant improvement in the outcome of this population.
authors.affiliation: Department of Internal Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy. a.nicolini@int.med.unipi.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Nicolini
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Paola
authors.initials: P
authors.lastname: Ferrari
authors.forename: Angelo
authors.initials: A
authors.lastname: Carpi
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D054697:Cytostatic Agents / Q000627:therapeutic use*; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D054697:Cytostatic Agents; D002955:Leucovorin; D005472:Fluorouracil