Clinical application of immunoreactivity of dihydropyrimidine dehydrogenase (DPD) using highly specific antibody against recombinant human DPD (rhDPD) in gastric scirrhous cancer treated with S-1, new DPD inhibitory fluoropyrimidine

Abstract

14053 Background: Highly specific antibody against recombinant human dihydropyrimidine dehydrogenase (DPD) has been developed to assess immunohistochemically DPD expression in tumors. A new oral DPD inhibitory fluoropyrimidine (DIF), S-1, is reportedly effective against gastric scirrhous cancer. Objective of this study was to assess intra-tumoral levels of DPD immunohistochemically using highly specific anti-DPD polyclonal antibodies, and investigated the relationship between the immunoreactivity of DPD and the anti-tumor effects of S-1 as a DIF in gastric scirrhous cancer patients. Methods: The relationship between immunoreactivity to DPD in biopsy specimens and the effects of chemotherapy was investigated in 61 patients treated with first-line fluoropyrimidine-based chemotherapy (S-1:DIF, 5-FU:non-DIF) for gastric scirrhous cancer. Immunohistochemical staining intensity was semiquantitatively graded (− to 3+) on the basis of the proportion of positively stained cancer cells in the lesions. Results: Total 61 gastric scirrhous cancer patients (M/F: 34/27) were analyzed to date with a median age of 56 (range 30–73). Response rate (partial response) was significantly higher in patients with DPD positive tumors than in those with negative in S-1 group (45.5%, 10.0% : p<0.05), as compared with in 5-FU group (0%, 5.6%: p=0.398). According to median survival time, there was no significant difference between patients with DPD positive tumors (364 days) and those with negative (406 days; p=0.626) in S-1 group or in 5-FU group (181 days and 256 days, respectively; p=0.543). Conclusions: This study indicates that S-1 is effective even in gastric scirrhous cancer with the high level of DPD activity. Further immunohistochemical studies using DIF-based regimens are needed to confirm these results with larger numbers of patients. No significant financial relationships to disclose.