Evidence map›Paper›PMID 23999218›Full record

ReviewNature reviews. Clinical oncology2013

Drug rechallenge and treatment beyond progression--implications for drug resistance.

Elizabeth A Kuczynski, Daniel J Sargent, Axel Grothey, Robert S Kerbel

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Nature reviews. Clinical oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03103724 (A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer), which is not on this map. Cited by 143 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
143citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03103724 phase2completednot on this mapstarted 2017, after this paper: background citation

A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients With Visceral Disease.

TypeinterventionalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2017 to 2021Enrolled68ConditionsCarcinoma ProstateArmsXtandi
3 · Its place in the literature

Who cites it

143 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Review
  7. Real-world outcomes of [European journal of nuclear medicine and molecular imaging · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
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  13. Review
  14. Definition of lines of treatment in metastatic colorectal cancer: a Delphi consensus.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  15. Article
  16. Review
  17. Article
  18. NBR1-Mediated Autophagic Degradation of YTHDF1 CurtailsCancer communications (London, England) · 2026
    Article
  19. Review
  20. Review

83 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Elizabeth A KuczynskiDepartment of Medical Biophysics, University of Toronto, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
Daniel J Sargent
Axel Grothey
Robert S Kerbel

Funding

TUMOR-HOST INTERACTIONS IN HUMAN MELANOMA METASTASISR01CA041233 · NCI · TORONTO-SUNNYBROOK REGIONAL CANCER CTR · PI KERBEL, ROBERT S · 1986 to 2013
$2.4M
CIHRNCI NIH HHS R01 CA041233
6 · The paper itself

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.

Indexed as

Antineoplastic AgentsDisease ProgressionDrug-Related Side Effects and Adverse ReactionsDrug Resistance, NeoplasmHumansNeoplasmsAntineoplastic Agents

Identifiers

PMID23999218
PMCPMC4540602

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.