Older Women Have More Chemo-Induced Neutropenia But Few Clinical Consequences

BALTIMORE--Adjuvant chemotherapy regimens for breast cancer are often reduced for patients over age 65 due to concerns about toxicity. These reductions may not be necessary in most cases. Elizabeth Claire Dees, MD, and her colleagues at the Johns Hopkins Oncology Center found that although older women had more neutropenia, this seldom resulted in clinical complications.

These results indicate that "otherwise healthy older women with breast cancer should not be excluded from adjuvant chemotherapy clinical trials," Dr. Dees said at the ASCO annual meeting.

Dr. Dees’ study prospectively measured neutrophil counts, cardiotoxicity, and quality of life in 44 women with early-stage breast cancer who were treated with a standard adjuvant therapy regimen. The women ranged in age from 35 to 79 years, and 11 were over age 65. All had nonmetastatic, ER-negative breast cancer (either node-negative or node-positive).

All subjects had a baseline left ventricular ejection fraction greater than 45%; adequate renal, hepatic, and hematopoietic function; and no history of congestive heart failure or cardiac disease.

Treatment was four cycles of AC--doxorubicin (Adriamycin) 60 mg/m² IV and cyclophosphamide 600 mg/m² IV--every 21 days. Bone marrow granulocyte progenitor cells were assayed in vitro for dose response to 4-hydroxy-C and doxorubicin prior to treatment.

Nadir absolute neutrophil count (ANC) decreased somewhat with age, about 10 cells for every year increase in age, Dr. Dees said. ANC was significantly lower in patients over age 65 after 4 cycles of AC (94 vs 270 cells/dL), but this did not result in any significant increase in the number of patients needing hospitalization for complications.

Furthermore, when the data were reanalyzed using age as a categorical variable (age less than 65 vs age 65 or greater), a similar proportion of women in each group reached a clinically significant nadir, ANC less than 100 (18% vs 19%, respectively).

There were no significant differences in changes in cardiac function or in quality of life indices pre- and post-treatment for older patients compared with younger ones. Age also had no effect on drug clearance rates.

"It is not clear from our data that this regimen needs to be modified for older patients," Dr. Dees said. "We did see a trend toward neutropenia after the fourth cycle, so in regimens that are more myelosuppressive or require more cycles of therapy than this one, there may be a role for growth factor support or prophylactic antibiotics in women over age 65."