Cost associated with chemotherapy-related adverse events

Costs were computed as the total of plan paid plus patient paid amounts, presented at constant 2013 US dollars.14,15 In this study, we evaluated costs related to outpatient visits, ER visits, hospitalizations, and other medications that were used to help treat the adverse events. The list of other medications was created using prior studies9 and with clinician feedback (Supplementary materials). We computed total costs related to the adverse events for each EOC to evaluate which adverse event was driving increase in costs. The average cost per EOC for each adverse events category was calculated by adding all costs of the visit types that created each EOC and dividing by the number of EOC. The KPSC 2013 sample charge amounts were used for hospital stays.14 KPSC 2013 sample fee schedules were used for various outpatient and ER visits.15 In previous studies,59 chemotherapy costs were included in the economic evaluation. However, in this study, we did not include chemotherapy costs because it was not the focus of our study. The list of other medications for these adverse events, including antiemetics, growth factors, electrolytes, and anti-infectives (Supplementary materials), was calculated using combination of public costs such as Redbook and,17 Each EOC, when identified, was started with an admission date and ended with a discharge date using the last visit for that particular EOC. The other medications were identified within each EOC by using the dispense date within the admission date of each EOC until the discharge date of the last visit, which ended the EOC.

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Statistical analyses

Unadjusted descriptive statistics were conducted to summarize characteristics of patients with mBC who experienced chemotherapy-related adverse events versus those who did not experience chemotherapy-related adverse events. Differences between these patients groups were tested using two-sided t-test for continuous variables and the chi-squared statistic for categorical variables. Costs were calculated for each EOC, and data were analyzed using SAS version 9.2 (SAS Institute, Cary, NC, USA). P-values <0.05 were considered to be statistically significant.


A total of 1,682 patients were identified after applying all inclusion and exclusion criteria (Supplementary materials). Patients initially started with a single chemotherapy agent versus combination chemotherapy regimen. First-line chemotherapy was categorized into patients initially starting on single or combination therapies consisting of capecitabine (67%), taxane (22%), cyclophosphamide (9%), doxorubicin (6%), and gemcitabine, epirubicin, vinorelbine, ixabepilone, and eribulin were 5%. Patients were on first-line therapy for a mean 262 days (SD ±105). There were 909 patients (54%) who had at least one or more identified adverse event and 773 (46%) who did not experience the identified adverse events during follow-up. Overall, there was a higher percentage of patients <65 years (60%) with a mean age of 53 years (SD ±8.1). Overall, both groups were similar between baseline comorbidities, but there were some statistical differences in race and peripheral vascular disease. Patients were predominantly white (57%), and most common comorbidities were hypertension (43%), diabetes (16%), chronic pulmonary disease (12%), and renal disease (9%; Table 1).

(To view a larger version of Table 1, click here.)

According to Table 2, there were a total of 5,475 episodes (4,185 single episodes [76.4%] and 1,290 multiple episodes [23.6%]) related to adverse events. The most prevalent episodes were hematological (33%), musculoskeletal/pain related (21%), gastrointestinal (19%), and infections/pyrexia (16%). Within single episodes, hematological (33.1%), musculoskeletal/pain related (25.6%), and gastrointestinal (18.5%) were the most frequent adverse events. However, within multiple episodes, hematological (32.6%) followed by infections/pyrexia (25.9%) and gastrointestinal (22.6%) were the most frequent adverse events.

(To view a larger version of Table 2, click here.)