Background: Capecitabine was shown to prolong overall survival in patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy based on the CREATE-X study. The starting dose of capecitabine in CREATE-X was 1250 mg/m2 twice per day on days 1-14 every 3 weeks whereas the United States (US) standard dosing of capecitabine is 1000 mg/m2. Fluoropyrimidine toxicity is higher in the US compared to East Asia. The goal of this study was to evaluate the tolerance of capecitabine at an urban clinic in the US consisting of predominantly non-Asian patients. . Methods: We performed a retrospective chart review of patients with TNBC with residual disease after neoadjuvant chemotherapy who were prescribed capecitabine from June 1, 2017 through June 1, 2021. Exclusion criteria included patients who received capecitabine concurrently with radiation. All statistical analyses were conducted using R software, version 4.1.0. Results: There were 64 patients who met criteria with an average age of 54 (SD 10) years. Of these patients, 13 (20.3%) were Hispanic/Latino; 26 (40.6%) white, 17 (26.6%) African American, and 4 (6.3%) Asian. There were 28 patients (43.8%) prescribed the CREATE-X capecitabine dosing of 1250 mg/m2, 26 (40.6%) prescribed the US standard dosing of 1000 mg/m2, and 10 (15.6%) prescribed a different dosing regimen. Characteristics of patients prescribed capecitabine 1250 mg/m2 and 1000 mg/m2 are in Table 1. Of the 28 patients prescribed 1250mg/m2 dosing, 8 (28.6%) completed 8 cycles, all requiring dose reductions; 7 (25.0%) discontinued due to intolerance. Of the 283 patients in the CREATE-X study treated with 8 cycles of 1250 mg/m2, 107 (37.8%) completed capecitabine treatment with the planned dose compared to no patients in our cohort. Of the 26 patients prescribed 1000 mg/m2, 9 (34.6%) completed 8 cycles with 3 patients requiring dose reductions; 6 (23.1%) discontinued due to intolerance. The most common adverse events were hand-foot syndrome (HFS) in 48 patients (75.0%), nausea in 24 (37.5%), fatigue in 23 (35.9%), and diarrhea in 22 (34.4%). Adverse events based on starting dose of capecitabine can be found in Table 1. The logistic regression was fitted to test the effect of the starting dose of capecitabine on the incidence of dose change after adjusting for the co-variates. The higher starting dose has higher odds (OR 9.065, 95% CI 2.558, 38.190) to change the capecitabine dose at the significant level of 0.05 (Table 2). Conclusions: No patients in our cohort tolerated 8 cycles of the CREATE-X dosing of 1250 mg/m2 compared to 37.8% of the study population. Of the patients who completed 8 cycles of the US standard dosing of capecitabine 1000 mg/m2, 66.7% of patients completed the planned dose. This dose was not studied in CREATE-X. Trials in metastatic disease comparing these two doses demonstrated similar efficacy with less toxicity. Further studies are warranted in this curative intent population.

Table 1.

Characteristics by Starting Dose of Capecitabine

Capecitabine Dose
Characteristics 1250 mg/m2(N = 28) 1000 mg/m2(N = 26) 
Age – yrs   
Median (IQR) 53.5 [34.0, 65.0] 50.0 [30.0, 68.0] 
Ethnicity – no (%)   
Hispanic 5 (17.9) 6 (23.1) 
Not Hispanic 23 (82.1) 20 (76.9) 
Race – no (%)   
White 15 (53.6) 9 (34.6) 
Black/AA 5 (17.9) 8 (30.8) 
Asian 1 (3.6) 1 (3.8) 
Other 7 (25.0) 8 (30.8) 
Clinical Stage – no (%)   
6 (21.5) 1 (3.8) 
17 (60.7) 9 (34.6) 
5 (17.8) 15 (57.7) 
Unknown 0 (0) 1 (3.8) 
Adverse Event – no (%)   
HFS 22 (78.6) 19 (73.1) 
Diarrhea 9 (32.1) 10 (38.5) 
Fatigue 8 (28.6) 11 (42.3) 
Mucositis 1 (3.6) 1 (3.8) 
Capecitabine Dose
Characteristics 1250 mg/m2(N = 28) 1000 mg/m2(N = 26) 
Age – yrs   
Median (IQR) 53.5 [34.0, 65.0] 50.0 [30.0, 68.0] 
Ethnicity – no (%)   
Hispanic 5 (17.9) 6 (23.1) 
Not Hispanic 23 (82.1) 20 (76.9) 
Race – no (%)   
White 15 (53.6) 9 (34.6) 
Black/AA 5 (17.9) 8 (30.8) 
Asian 1 (3.6) 1 (3.8) 
Other 7 (25.0) 8 (30.8) 
Clinical Stage – no (%)   
6 (21.5) 1 (3.8) 
17 (60.7) 9 (34.6) 
5 (17.8) 15 (57.7) 
Unknown 0 (0) 1 (3.8) 
Adverse Event – no (%)   
HFS 22 (78.6) 19 (73.1) 
Diarrhea 9 (32.1) 10 (38.5) 
Fatigue 8 (28.6) 11 (42.3) 
Mucositis 1 (3.6) 1 (3.8) 

Table 2.

Odds Ratio

95% CI
VariableORLCLUCLp-value
Capecitabine Dose 1250 mg/m2 9.065 2.558 38.190 0.000 
 1000 mg/m2 Ref    
Age (yr) > 65 6.421 0.477 163.895 0.158 
 < 65 Ref    
Ethnicity Hispanic 1.449 0.155 15.407 0.744 
 Non-Hispanic Ref    
Race Asian 1.201 0.028 57.156 0.992 
 Black/AA 1.045 0.209 5.522  
 Other 1.387 0.157 12.926  
 White Ref    
Chemo Carbo 1.680 0.439 6.679 0.447 
 No carbo Ref    
HFS Yes 0.920 0.196 4.154 0.913 
 No Ref    
95% CI
VariableORLCLUCLp-value
Capecitabine Dose 1250 mg/m2 9.065 2.558 38.190 0.000 
 1000 mg/m2 Ref    
Age (yr) > 65 6.421 0.477 163.895 0.158 
 < 65 Ref    
Ethnicity Hispanic 1.449 0.155 15.407 0.744 
 Non-Hispanic Ref    
Race Asian 1.201 0.028 57.156 0.992 
 Black/AA 1.045 0.209 5.522  
 Other 1.387 0.157 12.926  
 White Ref    
Chemo Carbo 1.680 0.439 6.679 0.447 
 No carbo Ref    
HFS Yes 0.920 0.196 4.154 0.913 
 No Ref    

Citation Format: Alaina Justine Kessler, Natalie S. Berger, Hsin-Hui Huang, Deborah Blythe Doroshow, Paula Klein. The tolerance of CREATE-X capecitabine dosing in a United States patient population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-12-02.