Abstract 668: Evaluation of α-1-acid glycoprotein as a prognostic marker and as a predictive biomarker for severe neutropenia induced by docetaxel in esophageal carcinoma patients
Authors: Yusuke Sasaki, Ken Kato, Hidekazu Hirano, Hirokazu Shoji, Yoshitaka Honma, Satoru Iwasa, Atsuo Takashima, Tetsuya Hamaguchi, Kengo Nagashima, Narikazu Boku
Journal: Cancer Research (2017)

Abstract Background: Serum α-1-acid glycoprotein (AAG) level is an independent predictor of response and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel chemotherapy. However, whether AAG is associated with the outcomes of esophageal cancer patients treated with docetaxel remains unclear. Methods: Between August 2009 and April 2014, pretreatment serum samples were obtained from patients with clinical stage II/III esophageal cancer. Individuals were subsequently treated with neoadjuvant DCF or CF followed by surgery. DCF consisted of docetaxel and cisplatin on day 1, and continuous infusion of 5-fluorouracil on days 1-5, with this regimen repeated every 3 weeks for up to three cycles. CF consisted of cisplatin and 5-fluorouracil. Patients were divided into groups based on the median value of baseline AAG levels. Response to chemotherapy, survival, and the most severe grade of neutropenia were compared between the high and low AAG groups at each regimen. Results: A total of 129 patients were enrolled (44 received neo DCF and 85 neo CF). The median serum AAG level was 95 g/L (range 57-228 g/L) and 95 g/L (range 46-197 g/L) in the patients with neo DCF and CF, respectively. For all patients, overall survival (OS) was significantly shorter in the high AAG group (AAG ≧ 95 g/L) than the low AAG group (AAG &amp;lt; 95 g/L) (HR 2.18, p=0.03). Both in the neo DCF and neo CF patients, there was a similar trend in OS between individuals with high and low AAG levels. Multivariate analysis demonstrated that AAG level (HR 1.98) and performance status (HR 2.20) were independent prognostic factors. However, the relationship between response to chemotherapy and AAG level were similar both in DCF and CF patients. In addition, grade 4 neutropenia was observed in 50% of patients with low AAG level and 23% with high AAG (p = 0.06) in DCF patients. A correlation analysis revealed a statistically significant correlation between serum AAG level and nadir absolute neutrophil count caused by DCF chemotherapy. However, in CF patients, there was no difference in the frequency of severe neutropenia between individuals with high and low AAG level, and there was no correlation between AAG and nadir neutrophil count. Conclusions: Serum AAG level may be a prognostic marker for survival in stage II/III esophageal cancer patients treated with neoadjuvant chemotherapy. In addition, low serum AAG level is a potential predictive biomarker of docetaxel-induced severe neutropenia. Citation Format: Yusuke Sasaki, Ken Kato, Hidekazu Hirano, Hirokazu Shoji, Yoshitaka Honma, Satoru Iwasa, Atsuo Takashima, Tetsuya Hamaguchi, Kengo Nagashima, Narikazu Boku. Evaluation of α-1-acid glycoprotein as a prognostic marker and as a predictive biomarker for severe neutropenia induced by docetaxel in esophageal carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 668. doi:10.1158/1538-7445.AM2017-668