New directions in the treatment of colorectal cancera look to the future

A. Sobrero, D. Kerr, B. Glimelius, E. Van Cutsem, G. Milano, D. M. Pritchard, P. Rougier, M. Aapro

Research output: Contribution to journalArticlepeer-review

Abstract

Today, adjuvant 5-fluorouracil based therapy is known to significantly reduce the relapse rates and the risks of dying from resected colon cancer; chemotherapy approximately doubles overall survival of advanced colorectal cancer and second line treatment prolongs the survival of patients compared with best supportive care. At the molecular level a number of key genes are often mutated in cancer of the colon and some of these key regulators of apoptosis are discussed (p53 and bcl-2 family of proteins). Dihydropyrimidine dehydrogenase (DPD) activity may be a potential factor controlling fluorouracil (FU) responsiveness at the tumoral level and its importance is stressed. The rationale of combining FU with DPD inhibitors is fairly strong. Ethynyluracil, UFT and S1 pursue this strategy while capecitabine has another the rationale. Drug resistance should be at least partially overcome by combination chemotherapy (FU plus mitomycin, oxaliplatin, irinotecan) and combined modality (FU+RT) regimens. Improved surgical techniques and radiotherapy have substantially decreased local failure rates for rectal cancers. Finally, innovative treatment modalities such as anti-angiogenetic and antimetastatic agents, farnesyl transferase inhibitors, vaccine and gene therapy are in early clinical trials. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalEuropean Journal of Cancer
Volume36
Issue number5
DOIs
Publication statusPublished - Mar 2000

Keywords

  • 5-FU
  • Apoptosis
  • Capecitabine
  • Colorectal cancer
  • Dihydropyrimidine dehydrogenase
  • Ethynyluracil
  • Irinotecan
  • Mitomycin
  • Oxaliplatin
  • p53
  • S1
  • Thymidylate synthase
  • UFT

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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