title: Drug rechallenge and treatment beyond progression--implications for drug resistance.
abstract: The established dogma in oncology for managing recurrent or refractory disease dictates that therapy is changed at disease progression, because the cancer is assumed to have become drug-resistant. Drug resistance, whether pre-existing or acquired, is largely thought to be a stable and heritable process; thus, reuse of therapeutic agents that have failed is generally contraindicated. Over the past few decades, clinical evidence has suggested a role for unstable, non-heritable mechanisms of acquired drug resistance pertaining to chemotherapy and targeted agents. There are many examples of circumstances where patients respond to reintroduction of the same therapy (drug rechallenge) after a drug holiday following disease relapse or progression during therapy. Additional, albeit limited, evidence suggests that, in certain circumstances, continuing a therapy beyond disease progression can also have antitumour activity. In this Review, we describe the anticancer agents used in these treatment strategies and discuss the potential mechanisms explaining the apparent tumour re-sensitization with reintroduced or continued therapy. The extensive number of malignancies and drugs that challenge the custom of permanently switching to different drugs at each line of therapy warrants a more in-depth examination of the definitions of disease progression and drug resistance and the resulting implications for patient care.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kuczynski
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kerbel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents