Toxopeus Eelke L A, de Man Femke M, Krak Nanda, Biermann Katharina, Nieuweboer Annemieke J M, Friberg Lena E, Oomen-de Hoop Esther, van Lanschot Jan J B, Shapiro Joel, Wijnhoven Bas P L, Mathijssen Ron H J
Department of Surgery, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Cancers (Basel). 2019 Feb 1;11(2):173. doi: 10.3390/cancers11020173.
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 (-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, -value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: -value = 0.08 and pCT: -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.
紫杉醇药代动力学的个体间差异可能在化疗反应中起作用。因此，我们研究了食管癌患者中紫杉醇清除率与治疗反应之间的关联。纳入了2007年至2013年间所有接受紫杉醇（加卡铂）治疗食管癌的患者。治疗方式为新辅助放化疗（nCRT）、诱导化疗（iCT）或姑息化疗（pCT）。分别通过肿瘤退缩分级（TRG）或RECIST1.1标准评估治疗反应。用NONMEM估算游离紫杉醇清除率（CL）。通过方差分析和独立样本t检验将对数转换后的清除率与反应相关联。共纳入166例患者，其中113例接受nCRT，23例接受iCT，30例接受pCT。在接受nCRT的患者中，紫杉醇清除率与肿瘤退缩分级（P值 = 0.25）无关，与病理完全缓解（几何均值561.6 L/h）和残留疾病（几何均值566.1 L/h，P值 = 0.90）也无关。在接受iCT或pCT的患者中，也未发现紫杉醇清除率与RECIST结果之间存在关联（iCT：P值 = 0.08，pCT：P值 = 0.81）。总之，全身性紫杉醇暴露与食管癌常见的基于紫杉醇的治疗方案的反应无关。未来的研究应关注肿瘤暴露与全身暴露及治疗结果的关系。
