title: Clinical Impact of Chemotherapy-Related Adverse Events in Patients with Metastatic Breast Cancer in an Integrated Health Care System.
abstract: BACKGROUND
  Stage IV breast cancer, also known as metastatic breast cancer (mBC), is not a curable condition. However, treatment can prolong life, delay the progression of the cancer, or improve quality of life. Currently, patients with mBC are often treated with chemotherapy. Patients often experience adverse events from chemotherapy during the treatment cycle, which leads to chemotherapy modifications such as dose delay, dose reduction, or discontinuation of chemotherapy. Previous studies have evaluated the rates of adverse events that occur from the use of chemotherapy; however, few studies have evaluated the clinical impact on the chemotherapy regimen once the adverse event occurs. This study evaluates the clinical impact on the chemotherapy regimen from chemotherapy-related adverse events in patients with mBC in an integrated health care delivery system.
  
  
  OBJECTIVE
  To assess the adverse events in patients with mBC and evaluate the clinical impact on the chemotherapy regimen from these adverse events in an integrated health care delivery system.
  
  
  METHODS
  This study is a retrospective cohort of patients with mBC newly initiated on chemotherapy. The first infusion was defined as the index date. Patients were aged greater than 18 years at time of index date and had 6 months or more of Kaiser membership and drug eligibility prior to the index date and continuous membership and drug eligibility throughout follow-up. Adverse events were identified after the index date and during the follow-up using ICD-9-CM diagnosis and procedure codes. Single or multiple episodes of care were created from the adverse events. Chart review was conducted to establish whether the adverse event was related to chemotherapy and if any modification to the chemotherapy regimen occurred-a dose delay, dose reduction, or discontinuation was considered a clinical impact on therapy. Multivariate logistic regression was used to examine factors associated with clinical impact versus no clinical impact from the delivery of chemotherapy treatment.
  
  
  RESULTS
  A total of 1,682 patients with mBC were identified during our time period with an average follow-up of 2.21 years on first-line chemotherapy (SD = 1.83). 909 patients (54%) had at least 1 adverse event, and 773 patients (46%) did not have any adverse events during follow-up. Significant differences at baseline between these 2 groups included race, peripheral vascular disease, and length of stay (P  less than  0.05). From the 909 patients who had at least 1 adverse event, 185 patients (20%) experienced an impact on their chemotherapy regimens. Patients with single episodes of care with any chemotherapy regimen impact experienced mostly hematological, infection/pyrexia, and gastrointestinal-related adverse events. In multiple episodes of care, neurological impact was more frequent than gastrointestinal-related effects. Patients with hospitalizations of greater than 3 days experienced the most impact, demonstrating that severe adverse events have more impact on chemotherapy regimens. In our multivariate analysis, patients aged greater than 65 years, having more than 1 comorbidity and having longer duration in days for each episode of care were all associated with clinical impact. Black and Hispanic patients were more likely to have a modification in their chemotherapy compared with white patients.
  
  
  CONCLUSIONS
  This retrospective analysis demonstrates that chemotherapy-related adverse events in patients with mBC have an impact on the delivery of chemotherapy regimens. Having multiple comorbidities, increased age, and prolonged hospitalizations because of adverse events appear to be some of the primary factors related to chemotherapy modification.
authors.affiliation: Kaiser Permanente Southern California, 12254 Bellflower Blvd., Downey, CA 90242. Nazia.X.Rashid@kp.org.
authors.forename: Nazia
authors.initials: N
authors.lastname: Rashid
authors.forename: Han A
authors.initials: HA
authors.lastname: Koh
authors.forename: Hilda C
authors.initials: HC
authors.lastname: Baca
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Li
authors.forename: Susan
authors.initials: S
authors.lastname: Malecha
authors.forename: Oyewale
authors.initials: O
authors.lastname: Abidoye
authors.forename: Anthony
authors.initials: A
authors.lastname: Masaquel
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D019033:Delivery of Health Care, Integrated; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007902:Length of Stay; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011788:Quality of Life; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents