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Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer
Erasmus Univ, Med Ctr, Dept Surg, Doctor Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands.
Erasmus Univ, Erasmus Med Ctr, Med Ctr, Canc Inst,Dept Med Oncol, Doctor Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands.ORCID iD: 0000-0001-7396-7050
Erasmus Univ, Med Ctr, Dept Radiol, Doctor Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands.
Erasmus Univ, Med Ctr, Dept Pathol, Doctor Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands.
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 2, article id 173Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2019. Vol. 11, no 2, article id 173
Keywords [en]
paclitaxel, esophageal cancer, treatment response, pharmacokinetics
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-380502DOI: 10.3390/cancers11020173ISI: 000460747200047PubMedID: 30717316OAI: oai:DiVA.org:uu-380502DiVA, id: diva2:1306425
Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved

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