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: Andrea Nicolini, Massimo Conte, Giuseppe Rossi, Paola Ferrari, Angelo Carpi, Paolo Miccoli
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 31 Issue 5 Pg. 523-32 (Oct 2010) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 20589491 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Cytostatic Agents
• Leucovorin
• Fluorouracil

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Cytostatic Agents (therapeutic use)
• Digestive System Surgical Procedures
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage)
• Gastrointestinal Neoplasms (drug therapy, mortality, pathology)
• Humans
• Kaplan-Meier Estimate
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (prevention & control)
• Neoplasm Staging
• Treatment Outcome