Adjuvant and neoadjuvant cancer therapies: A historical review and a rational approach to understand outcomes

Mauricio Burotto, Julia Wilkerson, Wilfred D. Stein, Susan E. Bates, Tito Fojo*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Drug development in oncology usually establishes efficacy in metastatic disease before advancing a therapy to the adjuvant or neoadjuvant settings. Unfortunately, too often use in adjuvant or neoadjuvant settings fails to improve overall survival. Reasons for the modest benefits include the fact that in many cases surgery cures a majority of patients making it difficult to demonstrate gains. We begin by looking at the history of adjuvant and neoadjuvant therapies and the principles guiding their development. We summarize accepted adjuvant and neoadjuvant therapies in several cancers and tabulate their outcomes. Then, extending our work on the growth and regression rate constants of tumors and the fraction of cells killed we demonstrate that therapies developed in the metastatic setting primarily delay tumor growth rather than kill more cells and argue this is a likely explanation for poor outcomes in adjuvant or neoadjuvant settings. We suggest a rational approach for enhancing success.

Original languageEnglish
Pages (from-to)83-99
Number of pages17
JournalSeminars in Oncology
Volume46
Issue number1
DOIs
StatePublished - Feb 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019

Keywords

  • Adjuvant therapy
  • Breast cancer
  • Colroectal cancer
  • Neo-adjuvant therapy
  • Targeted therapies
  • Tumor kinetics

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