Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer. METHODS: Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints. RESULTS: Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B. CONCLUSIONS: Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

[Usefulness of low-dose and long-term administration of imatinib in patients with liver metastases of rectal GIST and GIST of stomach].

Imatinib is an effective drug for KIT positive GIST, and the usual dose is 400 mg/day. On the other hand, imatinib sometimes causes leucopenia and it is hard to maintain a dosage of 400 mg/day. We reported here the two cases with a remarkable response of unresectable GIST using a low-dose and long-term administration of imatinib. It seems that a low dose and long-term administration of imatinib will be an important therapy for unresectable GIST.

[Usefulness of hepatic arterial infusion chemotherapy for the patients with synchronous liver metastases from colorectal cancer].

We analyzed the results of hepatic arterial infusion chemotherapy (HAIC) for 24 patients with synchronous liver metastases from colorectal cancer for the last twelve years in order to investigate the usefulness of HAIC for those patients. In 8 cases with resection of liver metastases, the median survival time (MST) was 45 months, mean survival time was 53 months and a 5-year survival rate was 44%. In 16 cases without resection of liver metastases, 2 cases had complete response (CR), 10 cases had partial response (PR), 4 cases had stable disease (SD), and the response rate was 75%. There was a significant difference in the survival time of each response. MST was 25 months, and mean survival time was 38 months. According to the usefulness of HAIC for the patients with synchronous liver metastases from colorectal cancer, it seems that HAIC with effective general chemotherapy will have better results than HAIC.

[Usefulness of hepatic arterial infusion chemotherapy for the patients with synchronous liver metastases from colorectal cancer].

We analyzed the results of hepatic arterial infusion chemotherapy (HAIC) for 21 patients with synchronous liver metastases from colorectal cancer for the last ten years to investigate the usefulness of HAIC for those patients. In 7 cases with resection of liver metastases, the median survival time (MST) was 49 months, mean survival time was 56.3 months and a 5-year survival rate was 43%. In 14 cases without resection of liver metastases, 2 cases had complete response (CR), 8 cases had partial response (PR), 4 cases had stable disease (SD), and the response rate was 71%. There was a significant difference in the survival time of each response. MST was 27 months, and mean survival time was 38.5 months. According to the usefulness of HAIC for the patients with synchronous liver metastases from colorectal cancer, it seems that HAIC with effective general chemotherapy will have better results than HAIC.

[A case of hepatocellular carcinoma of the caudate lobe relapsing with variable patterns after hepatectomy].

A 61-year-old man was referred for evaluation of positive HBs-Ag and an unusually high level (28,396 ng/mL) of serum alpha-fetoprotein in serum. Computed tomography of the abdomen revealed a huge extrahepatically growing tumor which was originating from the caudate lobe and extended to the posterior segment of the right lobe of the liver and encircled the anterior half of inferior vena cava. Biochemical examination showed a good liver function with 8% of ICG R15 and 103% of prothrombin time. Total resection of the caudate lobe with posterior segmentectomy was performed. Relapsing tumors, which metastasized to the liver in 9 months, the right lung in 15 months and the left lung in 20 months after initial surgery, were totally resected, respectively. Radiation therapy was effective to mediastinal lymph nodes metastasized in 25 months after the initial surgery. He survived with good quality of life for 46 months until he died from brain metastasis. Therefore, the multidisplinary therapy combined with radiation and surgery for hepatocellular carcinoma of the caudate lobe may have improved a long-term survival.

Immunohistochemical dihydropyrimidine dehydrogenase expression is a good prognostic indicator for patients with Dukes' C colorectal cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU), which is widely used for chemotherapy in patients with advanced colorectal cancer (CRC). However, the clinical importance of tumor dihydropyrimidine dehydrogenase (DPD) expression in patients with CRC treated with 5-FU remains unclear. MATERIALS AND METHODS: We investigated DPD activities in normal mucosa (N) and tumors (T) by enzyme-linked immunosorbent assay (ELISA) in 64 surgically resected patients with Dukes' C CRC who were treated orally with postoperative adjuvant FU-based chemotherapy. We also immunohistochemically investigated DPD expression in these specimens. The clinicopathological importance of DPD activity and expression was evaluated in the patients. RESULTS: Positive DPD expression was detected in 28 tumors (43.8%) and tumor DPD activity significantly correlated with tumor DPD immunoreactivity (p=0.0121). Further, tumor DPD activity and immunoreactivity also correlated with lymph node metastatic status (p=0.0409). The disease-free survival rate of patients with positive-tumor DPD expression was significantly worse than that of patients with negative-tumor DPD expression (39.3% vs. 72.2%, p=0.0127). However, DPD activity in tumors or normal mucosa did not correlate with patient prognosis. Tumor DPD expression appeared to be an important poor prognostic factor in patients with Dukes' C CRC by multivariate analysis (p=0.013). CONCLUSION: Immunohistochemical DPD expression in tumors is a useful prognostic parameter in patients with Dukes' C CRC treated with postoperative adjuvant FU-based chemotherapy.