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Prediction of neutrophil reduction using plasma paclitaxel concentration after administration in patients with uterine, ovarian, or cervical cancers in an outpatient clinic

Abstract

Purpose

Plasma paclitaxel (PTX) concentration 24 h or later after PTX administration may predict myelosuppression. Here, we explored predictive markers for neutropenia induced by intravenous administration of PTX in an outpatient clinic.

Methods

Thirty women suffering from uterine, ovarian or cervical cancer were enrolled in this study. PTX (mean dose: 167 mg/m2) was intravenously infused and followed by carboplatin. Plasma samples were obtained 4 h after PTX administration. Genotyping was carried out for CYP3A5*3, ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T.

Results

There was no significant relationship between genotype and reduced neutrophil count. Neutrophil reduction rate correlated with the patient’s height, neutrophil count on the day of administration, and plasma PTX concentration. Multiple regression analysis with those three indices explained 47.7% of the interindividual variability of the neutrophil reduction rate. The model with plasma PTX concentration, patient’s height, and plasma 6-α-hydroxy-paclitaxel /PTX concentration ratio also explained 30.0% of the interindividual variability for the neutrophil nadir count after PTX administration.

Conclusions

These results indicate that neutrophil reduction after PTX administration can be partially predicted by multiple regression analysis involving plasma concentration data collected at outpatient clinics.

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Acknowledgements

The genotyping assistance of Mrs. Ayami Sakakibara and Mr. Kiyoaki Ishino (Laboratory of Clinical Pharmaceutics) was greatly appreciated. This study was supported by JSPS KAKENHI Grant number JP22590138.

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Correspondence to Yoshiyuki Kagawa.

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We have no conflicts of interest to declare in relationship to this study.

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Ishikawa, M., Kawai, M., Maeda, T. et al. Prediction of neutrophil reduction using plasma paclitaxel concentration after administration in patients with uterine, ovarian, or cervical cancers in an outpatient clinic. Cancer Chemother Pharmacol 81, 399–411 (2018). https://doi.org/10.1007/s00280-017-3506-3

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Keywords

  • Paclitaxel
  • Outpatient clinic
  • Neutrophil reduction
  • 6-α-hydroxy-paclitaxel
  • Ovarian cancer