Abstract A69: Efficacy of alternative 28-day capecitabine dosing schedule in metastatic breast cancer
Authors: Williams Nicole Olivia , Suresh Anupama , Stephens Julie , Palettas Marilly , Berger Michael J. , Ganju Akaansha , Reinbolt Raquel , Wesolowski Robert , Noonan Anne M. , VanDeusen Jeffrey Bryan , Sardesai Sagar , Lustberg Maryam , Lustberg Maryam B. , Ramaswamy Bhuvaneswari 
Published: August 2018

Abstract
Background: The approved dosing schedule of capecitabine monotherapy in metastatic breast cancer (MBC) is 1250 mg/m2/dose administered days 1 through 14 of a 21-day cycle, but many patients (pts) have difficulty with this schedule due to side effects. Use of a lower starting dose such as 1000 mg/m2/dose or use of an alternative 28-day administration schedule (7 day on, 7 day off, repeat) allows for greater tolerability. Given limited data regarding efficacy of the alternative 28-day schedule, the primary objective of this study was to compare the efficacy of different schedules of capecitabine in patients with MBC.
Methods: A retrospective chart review of pts with metastatic breast cancer who received capecitabine as monotherapy between 2002 and 2014 at the Ohio State University James Cancer Hospital was performed. We excluded any HER2-positive patients who had received concurrent HER2-targeted therapy. Pts who initiated therapy at a dose of 1000 mg/m2/dose were classified by these dosing schedules: Arm A (21 day), B (28 day), and C (changeover from 21 day to 28 day). Time to treatment failure (TTF) and overall survival (OS) were compared between dosing schedules using Kaplan Meier curves and log-rank tests.
Results: A total of 181 MBC patients (Arm A: n = 113, Arm B: n = 25, Arm C: n = 43) with the following patient characteristics met eligibility criteria; 86.2% Caucasians, 13.8% non-Caucasians, 64.64% estrogen receptor (ER)-positive, 3.31% ER positive/HER2-positive, 2.22% ER negative/HER2-positive, and 29.83% triple-negative. The HER2-positive patients were excluded as they received concurrent therapy. A significant difference was seen in TTF (Arm A: 2.7 mo, Arm B: 2.8 mo, Arm C: 7.1 mo, p = 0.001) when comparing all dosing schedules as well as in OS (Arm A: 5.7 yrs, Arm B: 9.6 yrs, Arm C: 7.8 yrs, p = 0.006). After an initial dose reduction, patients on Arm B tolerated capecitabine for a longer period of time than patients on Arm A before needing a second dose reduction (Table 1). The median time on capecitabine for Arm A was 11.9 weeks and 12.6 weeks for Arm B, and the mean time of both Arm A and Arm B on capecitabine was 22.2 weeks. Patients with ER-positive breast cancer had improved TTF (4.45 months vs 2.32 months, p &lt; 0.001) and OS (7.26 years vs 3.99 years, p &lt; 0.001) compared to ER-negative breast cancer. Caucasians had improved TTF compared to African Americans (AA) and other races (3.90 mo vs 2.87 mo, p = 0.004); however, there was no significant difference in OS.
Median starting dose (mg/m2): Arm A - 1000; Arm B - 1043; Arm C - 1000
Time to 1st dose reduction (weeks): Arm A - 6; Arm B - 6; Arm C - 6.5
Dose after 1st reduction (mg/m2): Arm A - 808; Arm B - 848.5; Arm C - 802
Time to 2nd dose reduction (weeks): Arm A - 6; Arm B - 20; Arm C - 8
Dose after 2nd reduction (mg/m2): Arm A - 599.5; Arm B - 690; Arm C - 697
Time to 3rd dose reduction (weeks): Arm A - 6; Arm B - 0; Arm C - 24
Dose after 3rd reduction (mg/m2): Arm A - 575; Arm B - 0; Arm C - 557
Table 1: Median dose (mg/m2) and median time to reductions (in weeks)
Conclusions: Our study shows that patients who received the 28-day cycle initially or who were switched to the 28-day cycle appeared to have improved TTF and OS compared to patients on the 21-day cycle. It also shows that AA women had worse TTF on capecitabine when compared to Caucasians. One hypothesis for the improved TTF and OS is that this could be due to a higher total dose of capecitabine received in Arm B and C as shown in Table 1. We acknowledge that the limitations of our study include the sample size and the retrospective nature, and that further work needs to be done. However, the 28-day dosing schedule for capecitabine could be an alternative for elderly patients or patients with poor performance status who are at higher risk for drug toxicities.
Citation Format: Nicole Olivia Williams, Anupama Suresh, Julie Stephens, Marilly Palettas, Michael J. Berger, Akaansha Ganju, Raquel Reinbolt, Robert Wesolowski, Anne M. Noonan, Jeffrey Bryan VanDeusen, Sagar Sardesai, Maryam Lustberg, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. Efficacy of alternative 28-day capecitabine dosing schedule in metastatic breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A69.