Abstract
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.
Highlights
The incidence of esophageal cancer is still rising in the United States and Western Europe and mortality is high [1,2]
A total of 166 patients with esophageal cancer were included from a prospectively collected database, of whom 113 patients underwent neoadjuvant chemoradiotherapy followed by surgery
In patients receiving induction chemotherapy, a possible trend was seen towards patients with a clinical complete response having a lower paclitaxel clearance than patients with a partial response or stable disease
Summary
The incidence of esophageal cancer is still rising in the United States and Western Europe and mortality is high [1,2]. In approximately 30% of patients, no vital tumor cells are left in the esophagectomy specimen following neoadjuvant chemoradiotherapy (nCRT) [4,6,7]. In patients with extensive disease not amenable for surgery, induction or palliative chemotherapy (iCT or pCT, respectively) is given, where paclitaxel is combined with carboplatin [8,9,10,11]. In this setting, the dose of paclitaxel is higher (weekly 100 mg/m2 ) than in the neoadjuvant setting (weekly 50 mg/m2 )
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