Pharmacokinetic and biochemical analysis in the treatment of weekly paclitaxel in relapsed breast cancer

The mechanism(s) by which weekly paclitaxel exerted more therapeutic effica cy than the triweekly schedule in relapsed breast cancer is still unclear. To assess the rationale in therapeutic efficacy of weekly paclitaxel in rel apsed breast cancer, pharmacokinetic and biochemical analysed were examined in terms of the mean peak plasma concentration at 0 min (Cmax), 30 min, an d 24 h after finishing the infusion, and the extracellular domain of HER-2 in response to the treatment with paclitaxel. Twenty-five patients treated with weekly 1 h infusion of paclitaxel in the dose range from 40 mg/m(2) to 80 mg/m(2) were studied. Eleven patients responded to the treatment includ ing 4 cases of complete response (CR) and 7 cases of partial response (PR), while 14 patients did not respond including 12 cases of no change (NC) and 2 cases of progressive disease (PD). The plasma concentration of paclitaxe l and extracellular domain of HER-2 in the patients were measured by high-p ressure liquid chromatography and enzyme immunoassay, respectively. The pea k concentration (Cmax) and the other peaks at 30 min and 24 h in 10 patient s including 3 cases of 40 mg/m(2), 3 cases of 60 mg/m(2) and 4 cases of 80 mg/m(2) in the weekly paclitaxel were compared in proportion to the increas e of dose escalation, and compared to their tumor response. Further, the pl asma levels of extracellular domain of HER-2 in 17 patients treated with th e weekly paclitaxel were measured, and also compared to their tumor respons e. The mean Cmax treated with 40 mg/m(2), 60 mg/m(2) and 80 mg/m(2) in the weekly paclitaxel was 1.94, 2.18 and 1.54 muM, respectively. The dose escal ation of paclitaxel and the dose intensity were not correlated with the inc rease of plasma concentration of paclitaxel nor with the tumor response. In contrast, the plasma level of extracellular domain of HER-2 in responders was higher than that of non-responders in the weekly paclitaxel regimen(p=0 .0512, Mann-Whitney's U-test). These results suggest that tumor response to the weekly I h infusion of paclitaxel was not associated with the plasma c oncentration and the dose intensity, rather the plasma level of extracellul ar domain of HER-2 protein may be a predictor of tumor response in the trea tment of weekly paclitaxel in relapsed breast cancer.