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Open AccessCommunication

Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer

1
Department of Surgery, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
2
Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
3
Department of Radiology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
4
Department of Pathology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
5
Department of Pharmaceutical Biosciences, Uppsala University, Box 256, 751 05 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(2), 173; https://doi.org/10.3390/cancers11020173
Received: 4 December 2018 / Revised: 16 January 2019 / Accepted: 29 January 2019 / Published: 1 February 2019
Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome. View Full-Text
Keywords: paclitaxel; esophageal cancer; treatment response; pharmacokinetics paclitaxel; esophageal cancer; treatment response; pharmacokinetics
MDPI and ACS Style

Toxopeus, E.L.; de Man, F.M.; Krak, N.; Biermann, K.; Nieuweboer, A.J.; Friberg, L.E.; Oomen-de Hoop, E.; van Lanschot, J.J.; Shapiro, J.; Wijnhoven, B.P.; Mathijssen, R.H. Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer. Cancers 2019, 11, 173.

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