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This study was conducted to determine the recommended dose (RD) of intraperitoneal docetaxel (ID) in combination with systemic capecitabine and cisplatin (XP) and to evaluate its efficacy and safety at the RD in advanced gastric cancer (AGC) patients with peritoneal metastasis. AGC patients with peritoneal metastasis received XP ID, which consists of 937.5 mg/m2 of capecitabine twice daily on days 1–14, 60 mg/m2 of intravenous cisplatin on day 1, and intraperitoneal docetaxel at 3 different dose levels (60, 80, or 100 mg/m2) on day 1, every 3 weeks. In the phase I study, the standard 3 + 3 method was used to determine the RD of XP ID. In the phase II study, patients received RD of XP ID. In the phase I study, ID 100 mg/m2 was chosen as the RD, with one dose-limiting toxicity (ileus) out of six patients. The 39 AGC patients enrolled in the phase II study received the RD of XP ID. The median progression-free survival was 11.0 months (95% CI 6.9–15.1), and median overall survival was 15.1 months (95% CI 9.1–21.1). The most frequent grade 3/4 adverse events were neutropenia (38.6%) and abdominal pain (30.8%). The incidence of abdominal pain cumulatively increased in the later treatment cycles. Our study indicated that XP ID was effective, with manageable toxicities, in AGC patients with peritoneal metastasis. As the cumulative incidence of abdominal pain was probably related to bowel irritation by ID, it might be necessary to modify the dose.

Endoscopic submucosal dissection (ESD) has become accepted as the standard treatment for early gastric cancer. However, comparative outcomes of ESD and surgery have not been evaluated for adenocarcinoma in the esophagogastric junction (EGJ). We investigated the long-term outcomes of ESD compared with those of surgery for adenocarcinoma in the EGJ. Patients who underwent ESD or surgery for Siewert type II adenocarcinoma between 2005 and 2010 and who met the absolute and expanded criteria for endoscopic resection were eligible. Clinical features and treatment outcomes were retrospectively reviewed using medical records. Of the 79 patients included, 40 underwent ESD and 39 underwent surgery. During the median follow-up period of 60.9 months (range, 13.1–125.4 months), the 5-year overall survival rates were 93.9% and 97.3% for the ESD and surgery groups, respectively (p = 0.376). There were no gastric cancer-related deaths in either group. Adverse events occurred in 11 patients (13.9%) overall, and the incidence of treatment-related adverse events was similar between the two groups (10.0% vs. 17.9%, p = 0.308). ESD may be an effective alternative to surgery for the treatment of early gastric cancer in the EGJ based on the comparable long-term outcomes.

Oral fluoropyrimidine S-1 contains tegafur, which is metabolized to 5-fluorouracil by cytochrome P450 2A6 (CYP2A6). We here examined associations between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients. Patients received adjuvant S-1 (40 mg/m2 twice daily, days 1–28, every 6 weeks for eight cycles) after curative surgery for pathological stage II–III gastric cancer. We analyzed the wild-type allele (W) (CYP2A6*1) and four variant alleles (V) (CYP2A6*4, *7, *9, *10) that abolish or reduce this enzyme activity. Patients (n = 200) were enrolled between November 2007 and July 2013 with the following clinical characteristics: median age, 57 years (range, 32–83 years); 128 men, 72 women. With a median follow-up of 46.4 months, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 83.1 % (95 % CI, 77.7–88.5 %) and 94.8 % (95 % CI, 91.6–98.0 %), respectively. Genotype distributions were as follows: W/W (n = 49, 24.5 %), W/V (n = 94, 47.0 %), and V/V (n = 57, 28.5 %). Overall toxicity did not differ according to genotype for any grade (p = 0.612) or grade ≥3 (p = 0.143). However, RFS differed significantly according to CYP2A6 genotype. The 3-year RFS rates were 95.9 % for W/W, 83.1 % for W/V, and 72.5 % for V/V (p = 0.032). Carriers of W/V and V/V genotypes had a poorer RFS with a hazard ratio of 3.41 (95 % CI, 1.01–11.52; p = 0.049) and 4.03 (95 % CI, 1.16–13.93; p = 0.028), respectively, compared with the W/W genotype. CYP2A6 polymorphisms are not associated with toxicity of S-1 chemotherapy, but correlate with the efficacy of S-1 in the adjuvant setting for gastric cancer.

Postoperative chemotherapy with S-1 or capecitabine plus oxaliplatin is a standard treatment for resectable gastric cancer (GC). However, survival outcomes of stage IIIB–IV (M0) GC cases are still poor. We investigated the efficacy and safety of docetaxel, capecitabine, and cisplatin (DXP) in patients with stage IIIB–IV GC. This was a single-arm phase 2 study that included patients with stage IIIB–IV GC who underwent D2 gastrectomy. Patients received six cycles of docetaxel [60 mg/m2 on day 1 (D1)], capecitabine (1,875 mg/m2/day on D1–14), and cisplatin (60 mg/m2 on D1) every 3 weeks. The primary end-point was recurrence-free survival (RFS). A total of 46 GC patients between January 2007 and August 2008 were included. After a median follow-up of 56.1 months (range 52.2–64.1), the median RFS and overall survival (OS) were 26.9 months (95 % CI 7.5–46.4) and 43.9 months (95 % CI 29.2–58.7), respectively. The 5-year RFS and OS rates were 39.1 and 41.3 %, respectively. The most common grade 3/4 toxicities were neutropenia (40 %), anorexia (22 %), and febrile neutropenia (15 %). Adjuvant DXP is feasible and effective for patients with stage IIIB–IV GC. A phase 3 study comparing triplet and doublet regimens for these patients is ongoing.

A chemotherapy regimen with oxaliplatin, fluorouracil, and leucovorin is commonly used to treat advanced gastric cancer (AGC). This study was designed to compare the efficacy and the safety of oxaliplatin plus fluorouracil/leucovorin administered biweekly (mFOLFOX6) between elderly patients aged over 65 years and younger counterparts with AGC. This analysis included 82 AGC patients (≥65:31