Early Clinical Experience of Trastuzumab Plus Capecitabine/Cisplatin (HXP) Therapy for Patients with Unresectable Advanced Gastric Cancer

Background After the result of ToGA study, trastuzumab was introduced in Japan, which is the first molecular targeting therapy in the era of gastric cancer. Aims To investigate HER2 overexpression in advanced gastric cancer (stage 4) by immunohistchemistry using endoscopic biopsy samples. To discuss the feasibility and problems of trastuzumab plus capecitabine/cisplatin (HXP) therapy. Methods We investigated HER2 overexpression in 35 patients of advanced gastric cancer from March 2011 to December 2011. Among these, 12 patients revealed HER2 positive by endoscopic biopsy, and 9 patients were introduced HXP. As a rule, we investigated the overexpression of HER2 protein in all cases of unresectable gastric cancer by immunohistchemistry. Basically, we carried out endoscopic biopsy from different several sites (if possible six sites) of the main tumor, considering the heterogeneity of HER2 overexpression. Results We introduced HXP for five males and four females. Median age was 67. Tumor location: body/antrum/cardia = 6/2/1. Histology: well/moderately/poorly = 1/5/3. In four cases, HXP was carried out as the first-line chemotherapy, whereas the others had been received previous chemotherapy such as S-1 plus cisplatin (SP) therapy. Effect evaluation: CR/PR/SD/PD/NE = 0/2/3/2/2. Remarkable adverse events due to trastuzumab were seen in only one case; fever and chills considered as infusion reaction. On the other hand, six cases showed renal dysfunction. No one showed serious adverse events regarded as grade 3/4. Discussion Trastuzumab was well tolerated without significant adverse events in our clinical experience. Trastuzumab seems to be safe for elder patients. Due to renal dysfunction, whenever necessary we reduced or interrupted cisplatin administration and continued trastuzumab. There is no evidence for the efficacy of trastuzumab beyond second-line therapy and there remains a question whether it is effective to continue trastuzumab beyond PD. Therefore, future clinical trials can be expected in this regard.