Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer.

Abstract

BACKGROUND:

Reductions in adjuvant chemotherapy dose <85% for historical regimens (ie, cyclophosphamide/methotrexate/fluorouracil) are known to affect breast cancer survival. This threshold, in addition to early versus late dose reductions, are poorly defined for third-generation anthracycline/taxane-based chemotherapy. In patients with breast cancer receiving adjuvant 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-D), we evaluated the impact of chemotherapy total cumulative dose (TCD), and early (FEC) versus late (D only) dose reductions, on survival outcomes.

PATIENTS AND METHODS:

Women with stage I-III, hormone receptor-positive/negative, HER2-negative breast cancer treated with adjuvant FEC-D chemotherapy from 2007 through 2014 in Alberta, Canada, were included. TCD for cycles 1 to 6 of <85% or ≥85% was calculated. Average cumulative dose was also calculated for early (cycles 1-3) and late (cycles 4-6) chemotherapy. Survival outcomes (disease-free survival [DFS] and overall survival [OS]) were estimated using Kaplan-Meier and multivariate analysis. Cohorts were evaluated for uniformity.

RESULTS:

Characteristics were reasonably balanced for all cohorts. Overall, 1,302 patients were evaluated for dose reductions, with 16% being reduced <85% (n=202) relative to ≥85% (n=1,100; 84%). Patients who received TCD ≥85% relative to <85% had superior 5-year DFS (P=.025) and OS (P<.001) according to Kaplan-Meier analysis, which remained significant on univariate and multivariate analyses. In stratified late and early dose reduction cohorts, DFS and OS showed a significant inferior survival trend for dose reduction early in treatment administration in 5-year Kaplan-Meier (P=.002 and P<.001, respectively) and multivariate analyses (hazard ratio [HR], 1.46; P=.073, and HR, 1.77; P=.011, respectively). Dose delays of <14 or ≥14 days and granulocyte colony-stimulating factor use did not affect outcomes.

CONCLUSIONS:

Chemotherapy TCD <85% for adjuvant FEC-D affects breast cancer survival. Late reductions (D only) were not shown to adversely affect DFS or OS. Conversely, early reductions (FEC±D) negatively affected patient outcomes.

• Authors: Zachary Veitch, Omar F Khan, Derek Tilley, Patricia A Tang, Domen Ribnikar, Douglas A Stewart, Xanthoula Kostaras, Karen King, Sasha Lupichuk
• Journal: Journal of the National Comprehensive Cancer Network : JNCCN (J Natl Compr Canc Netw) Vol. 17 Issue 8 Pg. 957-967 (08 01 2019) ISSN: 1540-1413 [Electronic] United States
• PMID: 31390594 (Publication Type: Journal Article)

Topics

• Adult
• Aged
• Alberta (epidemiology)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (diagnosis, drug therapy, epidemiology, mortality)
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Comorbidity
• Female
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Treatment Outcome