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Cited by 180Breast Cancer Treatment StudiesCancer Treatment and PharmacologyFrailty in Older Adults

A prospective pharmacologic evaluation of age-related toxicity of adjuvant chemotherapy in women with breast cancer

Dees, E. Claire, O'reilly, Seamus, Goodman, Steven N., Sartorius, Susan, Levine, Marshall A., Jones, Richard J., Grochow, Louise B., Donehower, Ross C. +1 more·2000·Cancer Investigation
DOI 10.3109/07357900009012191
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Abstract

Despite increasing evidence of benefit from adjuvant chemotherapy, older women with breast cancer are commonly given less aggressive treatment than younger patients. Conflicting prior data regarding age-related toxicity prompted this prospective study. Forty-four women (aged 35-79 years) with early-stage breast cancer were treated with four cycles of adjuvant therapy with doxorubicin 60 mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v. every 21 days. They were monitored for myelosuppression, cardiotoxicity, and decrease in quality of life. Pharmacokinetics were analyzed using cycle 1 plasma samples. Bone marrow granulocyte and macrophage colony-forming units (CFU-GM) were assayed in vitro for dose response to 4-hydroperoxycyclophosphamide and doxorubicin before cycle 1. There was moderate evidence of age-related decrease in nadir absolute neutrophil count (ANC) when age was viewed as a continuous variable. On average there was a 10/microliter drop in cycle 1 nadir ANC for every year increase in age (p = 0.02). However, when age was viewed as a categorical variable (age < 65 vs. > or = 65 years), a similar proportion of women in each group reached an ANC < 100 (18% vs. 19%). Neither neutropenic complications, alteration in cardiac function, nor change in quality of life scores were significantly age related (p > 0.12). Pharmacokinetic analyses did not demonstrate age-related differences in the clearance of either doxorubicin or cyclophosphamide (p > 0.8). Pharmacodynamic analysis of individual patient bone marrow progenitor cell sensitivity did not reveal any correlation with age (p > 0.48). In women undergoing adjuvant therapy for breast cancer, no clinically significant age-related trends in toxicity were observed. These data suggest that older age alone should not exclude patients from receiving adjuvant therapy with doxorubicin and cyclophosphamide.

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Authors
Dees, E. C., O'reilly, S., Goodman, S. N., Sartorius, S., Levine, M. A., Jones, R. J., Grochow, L. B., Donehower, R. C., & Fetting, J. H.
Affiliations
  • Johns Hopkins Hospital (US)
  • Johns Hopkins University (US)
ORCID
Venue
Cancer Investigation
Publisher
Informa UK Limited
Published
2000-01
Volume
18
Issue
6
Pages
521-529
ISSN
  • 0735-7907 (ISSN-L)
  • 1532-4192
DOI
10.3109/07357900009012191
OpenAlex
W2096254008
Cited by
180
References
34
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 6 · 2012: 9
FWCI
3.52
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Investigation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Cancer Society
  • National Institutes of Health (5k12ca001709-13)
  • National Cancer Institute (CA 01709-03)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
Keywords
breast cancer, adjuvant chemotherapy, older women, age-dependent toxicity, doxorubicin, cyclophosphamide, myelosuppression, neutropenia, cardiotoxicity, quality of life, pharmacokinetics, pharmacodynamics, bone marrow progenitor cells, CFU-GM, early breast cancer
MeSH terms
Adult, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cyclophosphamide, Doxorubicin, Female, Hematopoietic Stem Cells, Humans, Middle Aged, Neutrophils, Prospective Studies, Quality of Life, Chemotherapy, Adjuvant

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