Abstract 5200: Significance of SPARC expression as the predict factor of the therapeutic effect of nab-PTX in gastric cancer

Abstract

Abstract Background: Gastric cancer is the most frequent cancer-related cause of death second only to lung cancer. Despite recent advances in chemotherapy and surgical techniques, 5-year survival for advanced or metastatic gastric cancer is around 5-20%. Chemotherapy is the standard palliative treatment in patients with an acceptable clinical status because it provides better survival and quality of life than supportive care. In Japan, paclitaxel (PTX) is commonly used as second-line chemotherapy for gastric cancer patients in practice, based on experiences with breast cancer and non-small-cell lung cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) is an intravenously administered microtubule inhibitor. Recently, nab-paclitaxel has become an option for patients with unresectable or recurrent gastric cancer who experienced progression despite 1st line chemotherapy. Secreted protein, acidic and rich in cysteine (SPARC) has the ability to bind albumin with a high affinity, therefore patients with SPARC expressing tumors could benefit from nab-paclitaxel treatment as the drug can be transported to the tumor in a targeted way and accumulates within at the tissue. SPARC was reported to be overexpressed in a variety of human malignancies, including glioma, colorectal, breast, esophageal, prostate, bladder, and thyroid carcinomas. SPARC plays multi-faceted contextual roles depending on the cancer type and whether it is produced by cancer cells or surrounding stromal cells. It has been reported that immunostaining of SPARC in these tumors revealed increased frequency and intensity of SPARC expression in fibroblasts rather than in tumor cells. Overexpression of the SPARC gene was observed in human gastric cancer, too. It has been suggested that this might lead to a higher effectivity and a better tolerance for the drug with less side effects. The aim of this study is to clarify the role of SPARC in gastric cancer. Method: The SPARC expression was assessed in 15 gastric cancer samples following surgical resection or biopsy used by immunohistochemistry. Result: The progression-free survival was longer in the SPARC high expression group than in the SPARC low expression group (p = 0.013). Overall survival was not significantly different in experimental groups. The incidences of grade 3 or 4 adverse effects were not different in both experimental groups. We also compared the expression of SPARC between biopsy samples before chemotherapy and resected sample after chemotherapy of the same cases. It was no difference in the SPARC expression of the samples before and after the chemotherapy. Conclusion: The expression of SPARC has been suggested to be a useful indicator for predicting the therapeutic effect of nab-PTX in gastric cancer. Citation Format: Yuki Kiyozumi, Junji Kurashige, Shiro Iwagami, Kenichi Nakamura, Mayuko Ohuchi, Daisuke Izumi, Keisuke Kosumi, Kazuto Harada, Ryuma Tokunaga, Yukiharu Hiyoshi, Yoshifumi Baba, Yasuo Sakamoto, Yuji Sakamoto, Naoya Yoshida, Hideo Baba. Significance of SPARC expression as the predict factor of the therapeutic effect of nab-PTX in gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5200. doi:10.1158/1538-7445.AM2015-5200