title: Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents.
abstract: BACKGROUND
  Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities. We sought to determine whether anticipation of low-grade toxicities and treatment logistics impact patient willingness to undergo therapy.
  
  
  METHODS
  A total of 209 patients with cancer (101 lung and 108 breast) were surveyed at the Vanderbilt-Ingram Cancer Center regarding willingness to comply with treatment based on anticipated efficacy, dosing convenience, and toxicity profiles. All toxicities were Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 1 and 2. Willingness to comply with treatment depending on toxicity, anticipated benefit, cancer type, and dosing convenience was compared.
  
  
  RESULTS
  A substantial number of patients (2.9%-48.8%, depending on the toxicity described) professed unwillingness to undergo treatment because of anticipated grade 1 and 2 toxicities. Gastrointestinal and constitutional toxicities had a stronger negative impact on patient willingness to undergo therapy than dermatologic toxicity. Patients with lung cancer were significantly more likely to accept dermatologic and gastrointestinal toxicities than those with breast cancer. Willingness to tolerate toxicities correlated with expected benefit in terms of life expectancy and chance of cure. Lengthy travel distance for treatment negatively impacted willingness to undergo treatment.
  
  
  CONCLUSIONS
  Anticipation of low-grade toxicities and dosing inconvenience negatively impacts patient willingness to be treated, which may affect adherence and therapeutic outcomes from therapy. Long-term tolerability should be considered when developing and assessing the impact of novel agents.
authors.affiliation: From the Division of Hematology and Oncology, Vanderbilt University Medical Center; Division of Quantitative Sciences, Vanderbilt University Medical Center; and Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Castellanos
authors.affiliation: From the Division of Hematology and Oncology, Vanderbilt University Medical Center; Division of Quantitative Sciences, Vanderbilt University Medical Center; and Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Sheau-chiann
authors.initials: SC
authors.lastname: Chen
authors.affiliation: From the Division of Hematology and Oncology, Vanderbilt University Medical Center; Division of Quantitative Sciences, Vanderbilt University Medical Center; and Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Hillary
authors.initials: H
authors.lastname: Drexler
authors.affiliation: From the Division of Hematology and Oncology, Vanderbilt University Medical Center; Division of Quantitative Sciences, Vanderbilt University Medical Center; and Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D019538:Health Care Surveys; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D057240:Patient Preference
chemical_list: D000970:Antineoplastic Agents