Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m and intravenous paclitaxel 50 mg/m on days 1 and 8 plus S-1 80 mg/m per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m per day on days 1 to 21 plus cisplatin 60 mg/m on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P = .080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P = .008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.

To determine the clinical efficacy of Roux-en-Y reconstruction (RY) after distal gastrectomy, we compared postoperative outcomes of patients who underwent RY or conventional Billroth I reconstruction (B-I). A total of 50 patients were prospectively randomized to either B-I or RY reconstruction, and complications, postoperative course, and nutritional status were compared. Bile reflux and inflammation in the remnant stomach and lower esophagus were evaluated by postoperative follow-up endoscopy at 6 months. Operative time and blood loss as well as postoperative nutrition did not show significant differences between the two groups. As anticipated, 5 of 24 patients with RY reconstruction developed gastrojejunal stasis in the early postoperative period, which led to a longer postoperative hospital stay as compared with the B-I group (mean +/- S.D; B-I; 19.0 +/- 6.2, RY; 31.8 +/- 21.7 days) (P < 0.05). Endoscopic examination revealed that the frequency of bile reflux (P < 0.01) and degree of inflammation in the remnant stomach (P < 0.05) were less in the RY group than in the B-I group. However, inflammatory findings in the lower esophagus were observed in 7 (27%) of B-I, and 8 (35%) of the RY group, suggesting that late phase esophagitis was not improved in the RY group. Roux-en-Y reconstruction was effective in preventing duodenogastric reflux and resulting gastritis, but it did not prevent esophagitis. Because RY reconstruction induces the frequent complication of Roux-en-Y stasis, causing longer postoperative hospital stay, this method has limited advantages over B-I anastomosis after distal gastrectomy.

This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

Background Serum tumor markers have been shown to correlate with the clinical status of patients with advanced gastric cancer. However, the clinical significance of each tumor marker in patients with peritoneal dissemination has not been fully verified. Methods Four serum markers, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA125, and CA72-4, were periodically measured in 102 patients with peritoneal dissemination who received combination intravenous and intraperitoneal chemotherapy. The initial values at diagnosis and after treatment were analyzed in association with clinicopathological factors, response to chemotherapy, and overall survival. Results The sensitivities of CEA, CA19-9, CA125, and CA72-4 for peritoneal metastasis at the initial diagnosis were 19, 36, 46, and 45%, respectively. The CA125 level was significantly correlated with the degree of peritoneal dissemination and the existence of malignant ascites. Patients with ovarian metastasis showed significantly higher levels of CA72-4. The median survival time of patients with an elevated CA125 level was significantly shorter than that of patients with a normal CA125 level (36.7 vs. 16.6 months, p \ 0.001). Multivariate analysis showed that the degree of peritoneal metastasis and an elevated CA125 level were independent prognostic factors. Normalization of the CA125 level after 3 courses of chemotherapy was correlated with reduced ascites and improved survival.Conclusions Serum CA125 and CA72-4 are clinically useful markers in diagnosis, evaluating the efficacy of chemotherapy, and predicting the prognosis of patients with peritoneal dissemination. From an academic point of view, periodic measurements of these markers are warranted in gastric cancer patients with possible peritoneal dissemination.

BACKGROUND:The prognosis of patients with gastric cancer with peritoneal metastasis is extremely poor. This phase 2 study evaluated the benefits and tolerability of weekly intravenous and intraperitoneal paclitaxel (PTX) treatment combined with oral S-1 in patients with gastric cancer who had macroscopic peritoneal metastasis. METHODS: Patients with gastric cancer who had primary tumors with macroscopic peritoneal metastasis were enrolled. PTX was administered intravenously at 50 mg/m 2 and intraperitoneally at 20 mg/m 2 on days 1 and 8, respectively. S-1 was administered at 80 mg/m 2 per day for 14 consecutive days, followed by 7 days of rest. The primary endpoint was the 1-year overall survival (OS) rate. The secondary endpoints were the response rate, efficacy against malignant ascites, and safety. RESULTS: Thirty-five patients were enrolled. The median number of treatment courses was 11 (range, 2-35). The 1-year OS rate was 77.1% (95% confidence interval, 60.5-88.1). The overall response rate was 71% in 7 patients with target lesions. Malignant ascites disappeared or decreased in 15 of 22 (68%) patients. The frequent grade 3/4 toxic effects were neutropenia (34%), leukopenia (23%), and anemia (9%). CONCLUSIONS: Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 is well-tolerated and effective in patients with gastric cancer who have macroscopic peritoneal metastasis. Cancer 2013;119:3354-8. V C 2013 American Cancer Society.KEYWORDS: phase 2 study; paclitaxel; S-1; gastric cancer; peritoneal metastasis; intraperitoneal chemotherapy. INTRODUCTIONGastric cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related deaths. 1 Multimodal therapy combined with systemic chemotherapy, radiation therapy, and surgery has been developed in the treatment of advanced gastric cancer. 2 Even for noncurable gastric cancer, many clinical trials have been conducted using various newly developed anticancer drugs. In a phase 3 study using docetaxel (DTX), cisplatin, and fluorouracil for recurrent or metastatic gastric cancer patients, the 1-year overall survival (OS) rate and median survival time (MST) were 40% and 9.2 months, respectively. 3 In another phase 3 study using S-1 and cisplatin for unresectable or recurrent gastric cancer, the 1-year OS rate and MST were 54.1% and 13.0 months, respectively. 4 Among patients with noncurable gastric cancer, the prognosis of patients with peritoneal metastasis is extremely poor, 5 and no standard treatment for peritoneal metastasis has been established.One potential treatment approach is the introduction of paclitaxel (PTX), which has been shown to produce a high response rate (29%-36%) for undifferentiated-type adenocarcinoma 6,7 and can be expected to show high efficacy for peritoneal dissemination. The intraperitoneal (IP) administration of PTX was developed to reinforce the drug's effect on peritoneal metastasis. This would be accomplished by making the drug act directly on the nodules at a high concentration. In ...

Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

Despite recent advances in chemotherapy, outcomes of patients with peritoneal metastases (PM) from gastric cancer are still very poor and standard treatment has not been established. Although oral S‐1 appears to be effective for patients with PM, the effects of systemic chemotherapy are limited. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) yield fewer benefits in patients with PM from gastric cancer than in patients with PM from other malignancies. In comparison, repeated intraperitoneal chemotherapy (RIPEC) with taxanes using an implantable peritoneal access port has a pharmacokinetic advantage for the control of peritoneal lesions and in combination with systemic chemotherapy can result in surprisingly long‐term survival in patients with PM from gastric cancer. Herein, we review the results of recent clinical studies specifically targeting PM from gastric cancer and discuss future prospects for an intraperitoneal approach to the ideal treatment of patients with gastric cancer with peritoneal involvement.