Skip to main content

The Economic Burden of Toxicities Associated with Cancer Treatment: Review of the Literature and Analysis of Nausea and Vomiting, Diarrhoea, Oral Mucositis and Fatigue


Side effects or toxicities are frequent, undesirable companions of almost all forms of non-surgical cancer therapy. It is unusual for patients to complete treatment with radiation or chemotherapy without experiencing at least one form of therapy-associated tissue injury or systemic side effect. Often, toxicities do not occur as solitary events; rather, they result in clusters of symptoms that share a common biological aetiology. Like any disease, cancer treatment-related toxicities (CTRTs) vary in their severity. But, in contrast to most diseases in which incidence is described as being present or absent, the current approach to CTRT typically limits reporting to severe cases only. Not only does this dilute the frequency with which CTRTs occur, but it also undermines our ability to determine the full burden of their impact and to accurately assess the cost effectiveness of potential toxicity interventions. In this article, we report the results of a directed literature review for the years 2000–2012, in which we studied and compared three tissue-based toxicities (nausea and vomiting, diarrhoea, and oral mucositis) and one systemic toxicity (fatigue). Our results confirm the heavy burden of resource use and cost associated with CTRTs. The inclusion of fatigue in our analysis provided an opportunity to compare and contrast a toxicity in which there are both acute and chronic consequences. Our findings also demonstrate a number of challenges to, and opportunities for, future study. Among the most obvious are the lack of provider consistency in diagnosis and grading, especially when there is no global agreement on severity scales. Compounding this inconsistency is the disconnect between healthcare providers and patients that exists when describing toxicity severity and impact. In many cases, cancer can be thought of as a chronic disease that requires prolonged but episodic treatment once the acute disease is eradicated. This change reflects increasing treatment successes, but it also implies that the burden of CTRTs will be expanded and prolonged. Creation of hierarchical attribution of costs in the presence of simultaneous CTRTs, accurate coding, and consistent tracking tools for toxicities will be imperative for effective appraisal of the costs associated with cancer treatment regimen toxicities.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Mariotto AB, Yabroff KR, Shao Y, et al. Projections of the cost of cancer care in the United States: 2010–2020. J Natl Cancer Inst. 2011;103(2):117–28.

    PubMed  Article  Google Scholar 

  2. 2.

    Surveillance, Epidemiology and End Results (SEER) Database (2012). Lifetime risk (percent) of being diagnosed with cancer by site and race/ethnicity: males, 18 SEER areas, 2007–2009 (Table 1.15) and females, 18 SEER areas, 2007–2009 (Table 1.16). Accessed May 2013.

  3. 3.

    Kim E, Dodd MJ, Aouizerat BE, et al. A review of the prevalence and impact of multiple symptoms in oncology patients. J Pain Symptom Manage. 2009;37(4):715–36.

    Article  Google Scholar 

  4. 4.

    Aprile G, Ramoni M, Keefe D, et al. Links between regimen-related toxicities in patients being treated for colorectal cancer. Curr Opin Support Palliat Care. 2009;3(1):50–4.

    PubMed  Article  Google Scholar 

  5. 5.

    Aapro M, Molassiotis A, Dicato M, et al. The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol. 2012;23(8):1986–92.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Haiderali A, Menditto L, Good M, et al. Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a US population. Support Care Cancer. 2011;19(6):843–51.

    PubMed  Article  Google Scholar 

  7. 7.

    Shih YC, Xu Y, Elting LS. Costs of uncontrolled chemotherapy-induced nausea and vomiting among working-age cancer patients receiving highly or moderately emetogenic chemotherapy. Cancer. 2007;110(3):678–85.

    Article  Google Scholar 

  8. 8.

    Craver C, Gayle J, Balu S, et al. Clinical and economic burden of chemotherapy-induced nausea and vomiting among patients with cancer in a hospital outpatient setting in the United States. J Med Econ. 2011;14(1):87–98.

    PubMed  Article  Google Scholar 

  9. 9.

    Burke TA, Wisniewski T, Ernst FR. Resource utilization and costs associated with chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting. Support Care Cancer. 2011;19(1):131–40.

    PubMed  Article  Google Scholar 

  10. 10.

    Hamada S, Hinotsu S, Hori K, et al. The cost of antiemetic therapy for chemotherapy-induced nausea and vomiting in patients receiving platinum-containing regimens in daily practice in Japan: a retrospective study. Support Care Cancer. 2012;20(4):813–20.

    PubMed  Article  Google Scholar 

  11. 11.

    Lordick F, Ehlken B, Ihbe-Heffinger A, et al. Health outcomes and cost-effectiveness of aprepitant in outpatients receiving antiemetic prophylaxis for highly emetogenic chemotherapy in Germany. Eur J Cancer. 2007;43(2):299–307.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Ballatori E, Roila F, Ruggeri B, et al. The cost of chemotherapy-induced nausea and vomiting in Italy. Support Care Cancer. 2007;15(1):31–8.

    PubMed  Article  Google Scholar 

  13. 13.

    Barrajon E, de las Peñas R. Randomised double blind crossover study comparing ondansetron, granisetron and tropisetron: a cost-benefit analysis. Support Care Cancer. 2000;8(4):323–33.

    Google Scholar 

  14. 14.

    Hartmann JT, von Vangerow A, Fels LM, et al. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. Br J Cancer. 2001;84(3):313–20.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Ihbe-Heffinger A, Ehlken B, Bernard R, et al. The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Ann Oncol. 2004;15(3):526–36.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Iihara H, Ishihara M, Matsuura K, et al. Pharmacists contribute to the improved efficiency of medical practices in the outpatient cancer chemotherapy clinic. J Eval Clin Pract. 2012;18(4):753–60.

    PubMed  Article  Google Scholar 

  17. 17.

    Lachaine J, Yelle L, Kaizer L, et al. Chemotherapy-induced emesis: quality of life and economic impact in the context of current practice in Canada. Support Cancer Ther. 2005;2(3):181–7.

    PubMed  Article  Google Scholar 

  18. 18.

    Elting L, Shih Y. The economic burden of supportive care of cancer patients. Support Care Cancer. 2004;12(4):219–26.

    PubMed  Article  Google Scholar 

  19. 19.

    Mittmann N, Verma S, Koo M, et al. Cost effectiveness of TAC versus FAC in adjuvant treatment of node-positive breast cancer. Curr Oncol. 2010;17(1):7–16.

    PubMed  CAS  Google Scholar 

  20. 20.

    Dranitsaris G, Maroun J, Shah A, et al. Estimating the cost of illness in colorectal cancer patients who were hospitalized for severe chemotherapy induced diarrhea. Can J Gastroenterol. 2005;19(2):83–7.

    PubMed  Google Scholar 

  21. 21.

    Dranitsaris G, Maroun J, Shah A, et al. Severe chemotherapy-induced diarrhea in patients with colorectal cancer: a cost of illness analysis. Support Care Cancer. 2005;13(5):318–24.

    PubMed  Article  Google Scholar 

  22. 22.

    Schwartzber LS, Sonis ST, Walker MS, et al. Single nucleotide polymorphism (SNP) Bayesian networks (BNs) predict risk of chemotherapy-induced side effects in patients with breast cancer receiving dose dense (DD) doxorubicin/cyclophosphamide plus paclitaxel (AC+T) [abstract no. 700107; poster no. P1-15-12]. San Antonio Breast Cancer Symposium; San Antonio; 4–8 Dec 2012.

  23. 23.

    Sonis ST, Schwartzber LS, Walker MS, et al. Predicting risk of chemotherapy-induced side effects in patients with colon cancer with single-nucleotide polymorphism (SNP) Bayesian networks (BNs). J Clin Oncol. 2012;30(Suppl 34);Abstract no. 344.

    Google Scholar 

  24. 24.

    Arbuckle RB, Huber SL, Zacker C, et al. The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study. Oncologist. 2000;5(3):250–9.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Elting LS, Cooksley C, Chambers M, et al. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98(7):1531–9.

    PubMed  Article  Google Scholar 

  26. 26.

    National Cancer Institute. Common terminology criteria for adverse events (CTCAE), version 4.0. Bethesda: US Department of Health and Human Services, National Institutes of Health; 2010.

  27. 27.

    Sonis ST, Oster G, Fuchs H, et al. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol. 2001;19(8):2201–5.

    PubMed  CAS  Google Scholar 

  28. 28.

    Elting LS, Cooksley CD, Chambers MS, et al. Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys. 2007;68(4):1110–20.

    PubMed  Article  Google Scholar 

  29. 29.

    Murphy BA, Beaumont JL, Isitt J, et al. Mucositis-related morbidity and resource utilization in head and neck cancer patients receiving radiation therapy with or without chemotherapy. J Pain Symptom Manage. 2009;38(4):522–32.

    PubMed  Article  Google Scholar 

  30. 30.

    Trotti A, Bellm LA, Epstein JB, et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003;66(3):253–62.

    PubMed  Article  Google Scholar 

  31. 31.

    Nonzee NJ, Dandade NA, Patel U, et al. Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis. Cancer. 2008;113(6):1446–52.

    PubMed  Article  Google Scholar 

  32. 32.

    Peterman A, Cella D, Glandon G, et al. Mucositis in head and neck cancer: economic and quality of life outcomes. J Natl Cancer Inst Monogr. 2001;29:45–51.

    PubMed  Article  Google Scholar 

  33. 33.

    Aprile G, Pisa FE, Follador A, et al. Unplanned presentations of cancer outpatients: a retrospective cohort study. Support Care Cancer. 2013;21(2):397–404.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Hassett MJ, O’Malley AJ, Pakes JR, et al. Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer. J Nat Cancer Inst. 2006;98(16):1108–17.

    PubMed  Article  Google Scholar 

  35. 35.

    McKenzie H, Hayes L, White K, et al. Chemotherapy outpatients’ unplanned presentations to hospital: a retrospective study. Support Care Cancer. 2011;19(7):963–9.

    PubMed  Article  Google Scholar 

  36. 36.

    Poirier Patricia. Factors affecting performance of usual activities during radiation therapy. Oncology Nursing Forum. 2007;34(4):827–34.

    PubMed  Article  Google Scholar 

  37. 37.

    Curt GA, Breitbart W, Cella D, et al. Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. Oncologist. 2000;5(5):353–60.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Lavigne JE, Griggs JJ, Tu XM, et al. Hot flashes, fatigue, treatment exposures and work productivity in breast cancer survivors. J Cancer Surviv. 2008;2(4):296–302.

    PubMed  Article  Google Scholar 

  39. 39.

    Lee MK, Lee KM, Bae JM, et al. Employment status and work-related difficulties in stomach cancer survivors compared with the general population. British J Cancer. 2008;98(4):708–15.

    Article  CAS  Google Scholar 

  40. 40.

    Greimel ER, Bjelic-Radisic V, Pfisterer J, et al. Toxicity and quality of life outcomes in ovarian cancer patients participating in randomized controlled trials. Support Care Cancer. 2011;19:1421–7.

    PubMed  Article  Google Scholar 

  41. 41.

    Fromme EK, Eilers KM, Mori M, et al. How accurate is clinician reporting of chemotherapy adverse events? A comparison with patient-reported symptoms from the Quality-of-Life Questionnaire C30. J Clin Oncol. 2004;22:3485–90.

    PubMed  Article  Google Scholar 

  42. 42.

    Ihbe-Heffinger A, Paessens B, Berger K, et al. The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care—an observational analysis on non-small-cell lung cancer patients. Support Care Cancer (Epub 2013 Jan 23).

  43. 43.

    Poirier P. The relationship of sick leave benefits, employment patterns, and individual characteristics to radiation therapy-related fatigue. Oncol Nurs Forum. 2006;33(3):593–601.

    PubMed  Article  Google Scholar 

Download references

Author Contributions

A. Carlotto, V. L. Hogsett and E. M. Maiorini contributed equally to the performance of searches, data summarization and manuscript preparation. J. G. Razulis analyzed data and contributed to the manuscript preparation. S. T. Sonis was the study principal investigator, contributed to the study design, data analysis and manuscript preparation, and is the overall guarantor of the study content.

Conflicts of Interest

The authors have no conflicts of interest related to the content of this manuscript.

Author information



Corresponding author

Correspondence to Stephen T. Sonis.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Carlotto, A., Hogsett, V.L., Maiorini, E.M. et al. The Economic Burden of Toxicities Associated with Cancer Treatment: Review of the Literature and Analysis of Nausea and Vomiting, Diarrhoea, Oral Mucositis and Fatigue. PharmacoEconomics 31, 753–766 (2013).

Download citation


  • Indirect Cost
  • Incremental Cost
  • Emergency Department Visit
  • Oral Mucositis
  • Aprepitant