Association between pharmacokinetic variables and neutropenia after treatment with docetaxel, cisplatin, and 5-fluorouracil in patients with esophageal squamous cell carcinoma

作者：Sugawara Mitsuhiro; Katada Chikatoshi^*; Komatsu Toshiaki; Takahashi Kaoru; Azuma Mizutomo; Higuchi Katsuhiko; Koizumi Wasaburo; Atsuda Koichiro

来源：Esophagus, 2015, 12(3): 209-218.

DOI：10.1007/s10388-014-0468-y

• Esophageal cancer
• DCF
• Neutropenia
• Pharmacokinetics
• Docetaxel

Combined chemotherapy with cisplatin, 5-fluorouracil, and docetaxel (DCF) is a promising regimen for the treatment of esophageal squamous cell carcinoma (ESCC). However, careful attention must be paid to severe neutropenia.
A total of 17 patients with ESCC who received DCF therapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and 5-fluorouracil 750 mg/m(2) on days 1-5) were studied from December 2010 through May 2012. We assessed the relation between neutropenia and the plasma concentration of each anticancer drug during the first course of DCF therapy.
The maximum plasma concentration (C (max)) (mean +/- A SD) of docetaxel was 1,929 +/- A 458 ng/mL, while that of cisplatin was 2,870 +/- A 410 ng/mL, and that of 5-fluorouracil was 448 +/- A 121 ng/mL. The area under the plasma concentration-time curve (AUC) (mean +/- A SD) as calculated by MOMENT analysis was 2,428 +/- A 513 ng/mL h for docetaxel and 135,950 +/- A 22,330 ng/mL h for cisplatin. The AUC of 5-fluorouracil was not calculated. Higher C (max) and AUC values for docetaxel were associated with trends toward lower nadir absolute neutrophil counts (ANCs). The C (max) of docetaxel reflected the AUC of docetaxel. Neither the C (max) nor AUC of docetaxel was related to the occurrence of febrile neutropenia.
Higher C (max) or AUC values of docetaxel are associated with a trend toward lower nadir ANCs in patients with ESCC who receive DCF therapy. The C (max) of docetaxel, which is assessable immediately after starting treatment, might be useful for predicting the severity of the nadir ANC or for selecting the management method.

• 出版日期2015-7