Advertisement

Toxicity-induced modification of treatment: what is in a name?

Published:October 20, 2018DOI:https://doi.org/10.1016/j.ejca.2018.09.018

      Highlights

      • Determinants of treatment-induced toxicities in patients with cancer need to be identified.
      • Current observational studies are hampered by a lack of a uniform definition for toxicity outcomes.
      • The term ‘toxicity-induced modification of treatment’ is proposed to summarise toxicities.
      • The definition includes a dose reduction, interruption, discontinuation or regimen switch.
      • Adopting this definition empowers comparisons across studies and communication between experts.

      Abstract

      Severe treatment-induced toxicities can have clinical consequences such as hospitalisation or treatment modifications, which in turn may deteriorate the prognosis of patients with cancer. Identification of determinants of treatment-induced toxicities is essential to develop strategies that promote therapy compliance and enhance the quality of life. Whereas toxicities are systematically recorded and graded per protocol in most clinical trials, observational studies often depend on retrospective data collection from medical records collected as standard care. Existing population-based or patient cohorts are a valuable source of information, even when relying on retrospective data collection, but comparisons across studies are hampered by a lack of a uniform definition for toxicity outcomes. We propose a new standardised approach to summarise toxicities in observational studies that rely on medical records for outcome assessment. We recommend the term ‘toxicity-induced modification of treatment’ (TIMT) to cover all toxicities that are responsible for changes in a planned treatment schedule. We define a TIMT as (i) a dose reduction, (ii) temporary interruption, (iii) discontinuation of therapy or (iv) an unanticipated switch to another regimen, as a result of treatment-induced toxicities and not because of progressive disease. This definition will provide clinically relevant information, especially when data on specific adverse events and Common Terminology Criteria for Adverse Events (CTCAE) grades are not uniformly available. Implementation of this definition empowers comparisons across studies, facilitates communication between clinicians and researchers and will allow new research questions in this active field of research.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Potter J.D.
        At the interfaces of epidemiology, genetics and genomics.
        Nat Rev Genet. 2001; 2: 142-147
        • Morris M.
        • Platell C.
        • Fritschi L.
        • Iacopetta B.
        Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients.
        Br J Cancer. 2007; 96: 701-707
        • Budman D.R.
        • Berry D.A.
        • Cirrincione C.T.
        • Henderson I.C.
        • Wood W.C.
        • Weiss R.B.
        • et al.
        Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer.
        JNCI: J Natl Cancer Inst. 1998; 90: 1205-1211
        • Mols F.
        • Beijers T.
        • Lemmens V.
        • CJvd Hurk
        • Vreugdenhil G.
        Poll-franse LVvd. Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: results from the population-based PROFILES registry.
        J Clin Oncol. 2013; 31: 2699-2707
        • Schmielau J.
        • Rick O.
        • Reuss-Borst M.
        • Kalusche-Bontemps E.M.
        • Steimann M.
        Rehabilitation of cancer survivors with long-term toxicities.
        Oncol Res Treat. 2017; 40: 764-771
        • Postel-Vinay S.
        • Collette L.
        • Paoletti X.
        • Rizzo E.
        • Massard C.
        • Olmos D.
        • et al.
        Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents – dose-Limiting toxicity and toxicity assessment recommendation group for early trials of targeted therapies, an European organisation for research and treatment of cancer-led study.
        European Journal of Cancer. 2014; 50: 2040-2049
        • Le Tourneau C.
        • Razak A.R.A.
        • Gan H.K.
        • Pop S.
        • Diéras V.
        • Tresca P.
        • et al.
        Heterogeneity in the definition of dose-limiting toxicity in phase I cancer clinical trials of molecularly targeted agents: a review of the literature.
        Eur J Cancer. 2011; 47: 1468-1475
        • Eisenhauer E.A.
        • O'Dwyer P.J.
        • Christian M.
        • Humphrey J.S.
        Phase I clinical trial design in cancer drug development.
        J Clin Oncol. 2000; 18 (684-684)
        • Cinausero M.
        • Aprile G.
        • Ermacora P.
        • Basile D.
        • Vitale M.G.
        • Fanotto V.
        • et al.
        New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury.
        Front Pharmacol. 2017; 8: 354
        • Lotfi-Jam K.
        • Carey M.
        • Jefford M.
        • Schofield P.
        • Charleson C.
        • Aranda S.
        Nonpharmacologic strategies for managing common chemotherapy adverse effects: a systematic review.
        J Clin Oncol. 2008; 26: 5618-5629
        • Tejpar S.
        • Yan P.
        • Piessevaux H.
        • Dietrich D.
        • Brauchli P.
        • Klingbiel D.
        • et al.
        Clinical and pharmacogenetic determinants of 5-fluorouracyl/leucovorin/irinotecan toxicity: results of the PETACC-3 trial.
        Eur J Cancer. 2018; 99: 66-77
        • Mourtzakis M.
        • Prado C.M.
        • Lieffers J.R.
        • Reiman T.
        • McCargar L.J.
        • Baracos V.E.
        A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care.
        Appl Physiol Nutr Metabol. 2008; 33: 997-1006
        • Kazemi-Bajestani S.M.R.
        • Mazurak V.C.
        • Baracos V.
        Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes.
        Semin Cell Dev Biol. 2016; 54: 2-10
        • O'Flanagan C.H.
        • Smith L.A.
        • McDonell S.B.
        • Hursting S.D.
        When less may be more: calorie restriction and response to cancer therapy.
        BMC Med. 2017; 15: 106
        • Wedlake L.
        • Shaw C.
        • McNair H.
        • Lalji A.
        • Mohammed K.
        • Klopper T.
        • et al.
        Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy.
        Am J Clin Nutr. 2017; 106: 849-857
        • Yan M.
        • Ho C.
        • Winquist E.
        • Jonker D.
        • Rayson D.
        • Stitt L.
        • et al.
        Pretreatment serum folate levels and toxicity/efficacy in colorectal cancer patients treated with 5-fluorouracil and folinic acid.
        Clin Colorectal Canc. 2016; 15 (e3): 369-376
        • Snyder C.F.
        • Aaronson N.K.
        • Choucair A.K.
        • Elliott T.E.
        • Greenhalgh J.
        • Halyard M.Y.
        • et al.
        Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations.
        Qual Life Res. 2012; 21: 1305-1314
        • Basch E.
        • Dueck A.C.
        • Rogak L.J.
        • Minasian L.M.
        • Kelly W.K.
        • O'Mara A.M.
        • et al.
        Feasibility assessment of patient reporting of symptomatic adverse events in multicenter cancer clinical trials.
        JAMA Oncol. 2017; 3: 1043-1050
        • Winkels R.M.
        • Heine-Broring R.C.
        • van Zutphen M.
        • van Harten-Gerritsen S.
        • Kok D.E.
        • van Duijnhoven F.J.
        • et al.
        The COLON study: colorectal cancer: longitudinal, observational study on nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life.
        BMC Canc. 2014; 14: 374
        • Kwan M.L.
        • Ambrosone C.B.
        • Lee M.M.
        • Barlow J.
        • Krathwohl S.E.
        • Ergas I.J.
        • et al.
        The pathways study: a prospective study of breast cancer survivorship within Kaiser Permanente Northern California.
        Cancer Causes Control. 2008; 19: 1065-1076
        • Bueno-de-Mesquita H.B.
        • Gonzalez C.A.
        Main hypotheses on diet and cancer investigated in the EPIC study. European prospective investigation into cancer and nutrition.
        Eur J Canc Prev. 1997; 6: 107-117
        • Jouinot A.
        • Vazeille C.
        • Durand J.P.
        • Huillard O.
        • Boudou-Rouquette P.
        • Coriat R.
        • et al.
        Resting energy expenditure in the risk assessment of anticancer treatments.
        Clin Nutr. April 2018; 37: 558-565
        • Arrieta O.
        • De la Torre-Vallejo M.
        • Lopez-Macias D.
        • Orta D.
        • Turcott J.
        • Macedo-Perez E.O.
        • et al.
        Nutritional status, body surface, and low lean body mass/body mass index are related to dose reduction and severe gastrointestinal toxicity induced by afatinib in patients with non-small cell lung cancer.
        Oncol. 2015; 20: 967-974
        • Banach M.
        • Juranek J.K.
        • Zygulska A.L.
        Chemotherapy-induced neuropathies—a growing problem for patients and health care providers.
        Brain Behav. 2017; 7e00558
        • Seruga B.
        • Templeton A.J.
        • Badillo F.E.V.
        • Ocana A.
        • Amir E.
        • Tannock I.F.
        Under-reporting of harm in clinical trials.
        Lancet Oncol. 2016; 17: e209-e219
        • Castellanos E.H.
        • Chen S.C.
        • Drexler H.
        • Horn L.
        Making the grade: the impact of low-grade toxicities on patient preference for treatment with novel agents.
        J Natl Compr Canc Netw. 2015; 13: 1490-1495
        • Ewer M.S.
        • Suter T.M.
        • Lenihan D.J.
        • Niculescu L.
        • Breazna A.
        • Demetri G.D.
        • et al.
        Cardiovascular events among 1090 cancer patients treated with sunitinib, interferon, or placebo: a comprehensive adjudicated database analysis demonstrating clinically meaningful reversibility of cardiac events.
        Eur J Cancer. 2014; 50: 2162-2170
        • Bayo J.
        • Prieto B.
        • Rivera F.
        Comparison of doctors' and breast cancer patients' perceptions of docetaxel, epirubicin, and cyclophosphamide (TEC) toxicity.
        Breast J. 2016; 22: 293-302
        • Roy S.
        • Trinchieri G.
        Microbiota: a key orchestrator of cancer therapy.
        Nat Rev Cancer. 2017; 17: 271-285
        • Giacomini K.M.
        • Yee S.W.
        • Mushiroda T.
        • Weinshilboum R.M.
        • Ratain M.J.
        • Kubo M.
        Genome-wide association studies of drug response and toxicity: an opportunity for genome medicine.
        Nat Rev Drug Discov. 2017; 16: 1
        • Rattner J.
        • Bathe O.F.
        Monitoring for response to antineoplastic drugs: the potential of a metabolomic approach.
        Metabolites. 2017; 7