Retrospective Analysis of Severe Neutropenia in Patients Receiving Concomitant Administration of Docetaxel and Clarithromycin

Abstract

Background: Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin. Methods: Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses. Results: One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia. Conclusions: This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression.

Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients

“…Several factors, such as female gender, [ 15 – 17 ] younger age, [ 18 – 20 ] lower BMI, [ 21 , 22 ] and lower pretreatment blood cell counts, [ 17 , 23 , 24 ] and hemoglobin levels, [ 19 , 25 – 27 ] were identified as risk factors for severe CIN and/or febrile neutropenia. However, a pharmacogenetic approach based solely on polymorphisms involved in antitumor agent activity appears to be insufficient.…”

The Glasgow Prognostic Score Predicts Response to Chemotherapy in Patients with Metastatic Breast Cancer

“…The mechanisms by which the systemic inflammatory response is involved in chemotherapy-related toxicities could be partially attributed to an alteration of the principal drug-metabolizing enzyme of chemotherapeutic agents, such as P450 3A cytochrome [31]. It has been reported that the activity of cytochrome P450 3A is compromised in cancer patients with an elevated CRP concentration [32].…”

Blood Concentration of Cabazitaxel in a Patient Whose General Condition Worsened with Concomitant Use of Clarithromycin

“…Cabazitaxel and docetaxel are metabolized mainly by CYP3A4 [2, 3], so concomitant use of either of these agents with a drug that affects CYP3A4 activity requires caution. Concomitant use of clarithromycin, which inhibits CYP3A4, with docetaxel has been reported to increase the plasma concentration of docetaxel and the risk of neutropenia [4]. Moreover, coadministration of ketoconazole, another strong CYP3A4 inhibitor, with cabazitaxel was reported to increase the area under the curve of cabazitaxel by around 25% [5].…”