Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials.

BACKGROUND: Ethnic differences in drug susceptibility and toxicity are a major concern, not only in drug development but also in the clinical setting. We review the toxicity profiles of docetaxel according to dose and ethnicity. METHODS: We analyzed phase II and III clinical trials that included a once-every-3-weeks single-agent docetaxel arm. Logistic regression analysis was applied to identify the significant variables affecting the reported incidence of docetaxel-induced severe neutropenia. RESULTS: Multivariate logistic regression analysis identified studies conducted in Asia [odds ratio (OR) 19.0; 95% confidence interval (95% CI) 3.64-99.0] and docetaxel dose (OR 1.08; 95% CI 1.03-1.13) as independent variables for the incidence of grade 3/4 neutropenia. CONCLUSIONS: There is a significant difference in the incidence of docetaxel-induced severe neutropenia between Asian and non-Asian clinical studies. Physicians and pharmacists should consider ethnic diversity in docetaxel toxicity when interpreting the results of clinical trials.

Predictors of response of patients with solid tumors to granulocyte colony-stimulating factor.

BACKGROUND: Granulocyte colony-stimulating factor administration is an important component of supportive therapy in chemotherapy-induced leukopenia. Although patient response to granulocyte colony-stimulating factor administration is known to vary, the factors responsible for poor response have not been identified. OBJECTIVE: To identify the predictors of the responses of patients with solid tumors to granulocyte colony-stimulating factor. SETTING: A 600-bed university hospital offering secondary and tertiary care in Japan. METHODS: This retrospective cohort study examined the response of 181 patients with solid tumors who were administered prophylactic granulocyte colony-stimulating factor for the first time after they developed severe grade 3/4 leukopenia (white blood cell count <2,000 × 10(-9)/L) because of adjuvant or neoadjuvant chemotherapy. The granulocyte colony-stimulating factor response was defined as the length of the leukocyte recovery period, which was assessed as the period within which the normal white blood cell count (white blood cell count >3,000 × 10(-9)/L) is reached after the first dosage of granulocyte colony-stimulating factor. After classification of the patients as either poor or normal granulocyte colony-stimulating factor responders according to the confidence interval of the recovery period, their characteristics were compared. MAIN OUTCOME MEASURE: The time for recovery to normal white blood cell count was 2-7 days (90 % confidence interval), and the cutoff value for differentiating poor responders (n = 14) from normal responders (n = 167) was 8 days. Univariate analysis identified previous radiotherapy, number of chemotherapy courses, high granulocyte colony-stimulating factor dosage, and hypoalbuminemia to be significantly associated with granulocyte colony-stimulating factor response. Multivariate analysis identified undergoing four or more chemotherapy courses (odds ratio = 5.09; 95 % confidence interval, 1.14-22.71) and heart failure (odds ratio = 5.96; 95 % confidence interval, 1.09-32.57) to be significantly associated with poor granulocyte colony-stimulating factor response. CONCLUSIONS: Undergoing four or more chemotherapy courses and heart failure are independent risk factors for poor response to granulocyte colony-stimulating factor. These findings may help prevent the complications of leukopenia during chemotherapy and highlight the need to develop better strategies for preventing and treating infectious disease in patients undergoing granulocyte colony-stimulating factor administration.