Effect of capecitabine on mean corpuscular volume in patients with metastatic breast cancer

Capecitabine is a novel oral chemotherapy agent designed to generate 5-fluorouracil (5-FU) preferentially in tumor tissue, and is the most effective therapy for anthracycline and taxane-resistant breast cancer. Macrocytosis has not been previously reported in association with capecitabine therapy. We performed a retrospective review of consecutive metastatic breast cancer (MBC) patients receiving standard 21-day cycles of oral capecitabine therapy at a single center during the year 2000. Patients were assessed prior to each cycle with clinical examinations and complete blood counts. Seventy-six women (median age 52 years, median follow-up 273 days) met inclusion criteria for the study. Prior to treatment, the average mean corpuscular volume (MCV) was 91.6 fl (normal range 80-100 fl). During chemotherapy, MCV increased in a dose-dependent and time-dependent manner. Fifty-seven percent of study patients developed macrocytosis (MCV > 100 fl) while on capecitabine therapy; 85% of women who received at least nine cycles of therapy exhibited macrocytosis. Development of macrocytosis was independent of anemia, thrombocytopenia, neutropenia, liver metastasis, and hepatic dysfunction; however, increases in MCV were more pronounced in 5-FU-naive patients. Alternative causes of macrocytosis were not identified in patients without coexisting anemia. We conclude that capecitabine therapy produces time-dependent and dose-dependent macrocytosis in MBC patients. However, macrocytosis was not associated with anemia or overt myelo-suppression. When capecitabine-treated breast cancer patients develop macrocytosis in the absence of anemia, investigations of other causes of macrocytosis are not warranted.