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

Despite increasing evidence of benefit from adjuvant chemotherapy, older wo men with breast cancer are commonly given less aggressive treatment than yo unger patients. Conflicting prior data regarding age-related toxicity promp ted 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/m(2) i.v. and cyclophosphamide 600 mg/m(2) i.v. every 21 days. They were monitored for myelosuppression, cardiotoxicity, and decreas e in quality of life. Pharmacokinetics were analyzed using cycle 1 plasma s amples. Bone marrow granulocyte and macrophage colony-forming units (CFU-GM ) were assayed in vitro for dose response to 4-hydroperoxycyclophosphamide and doxorubicin before cycle I. 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/mu l drop in cycle 1 nadir A NC for every year increase in age (p = 0.02). However, when age was viewed as a categorical variable (age < 65 vs. 165 years), a similar proportion of women in each group reached an ANC < 100 (18% vs. 19%). Neither neutropeni c complications, alteration in cardiac function, nor change in quality of l ife scores were significantly age related (p > 0.12). Pharmacokinetic analy ses did not demonstrate age-related differences in the clearance of either doxorubicin or cyclophosphamide (p > 0.8). Pharmacodynamic analysis of indi vidual patient bone marrow progenitor cell sensitivity did not reveal any c orrelation with age (p > 0.48). In women undergoing adjuvant therapy for br east cancer; no clinically significant age-related trends in toxicity were observed These data suggest that older age alone should not exclude patient s from receiving adjuvant therapy with doxorubicin and cyclophosphamide.