Evaluation of the efficacy of palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin.

PURPOSE: The purpose of our study was to evaluate the efficacy of a new combination antiemetic therapy consisting of palonosetron, aprepitant, and dexamethasone in gastric cancer patients undergoing chemotherapy with S-1 plus cisplatin. METHODS: This prospective, multi-institutional observational study assessed patient-reported nausea, vomiting, use of rescue therapy, change of dietary intake, and Functional Living Index-Emesis (FLIE) questionnaire results. The percentages of patients showing complete response (CR; no emesis and non-use of any rescue antiemetics) and complete protection (CP; no significant nausea and non-use of any rescue antiemetics), change of dietary intake, and impact of chemotherapy-induced nausea and vomiting on daily life during the overall (0-120 h after cisplatin administration), acute (0-24 h), and delayed (24-120 h) phases were examined. These findings were compared with our previous study, which used granisetron, aprepitant, and dexamethasone, to assess the relative effectiveness of palonosetron versus granisetron in combination antiemetic therapy. RESULTS: Of the 72 included patients, 66 (91.6 %), 70 (97.2 %), and 50 (69.1 %) achieved CR, and 48 (66.7 %), 61 (84.7 %) and 49 (68.1 %) achieved CP during in the overall, acute, and delayed phases of cisplatin administration, respectively. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 78.6 % of patients maintained their quality of life. Palonosetron was not superior to granisetron in combination antiemetic therapy. CONCLUSIONS: Three-drug combination antiemetic therapy with palonosetron, aprepitant, and dexamethasone was tolerable in gastric cancer patients undergoing treatment with S-1 plus cisplatin. The predominance of palonosetron to granisetron was not demonstrated in this study.

A randomized multicenter Phase II study of perioperative tiotropium intervention in gastric cancer patients with chronic obstructive pulmonary disease.

BACKGROUND: Tiotropium, a long-acting inhaled anticholinergic drug, has been widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the issue of whether perioperative tiotropium improves postoperative outcomes for gastric cancer patients with COPD remains unclear. Thus, the aim of this study was to determine the efficacy of perioperative tiotropium intervention for gastric cancer patients with COPD. PATIENTS AND METHODS: Eighty-four gastric cancer patients with mild-to-moderate COPD were randomly assigned to receive perioperative pulmonary rehabilitation alone (control group) or pulmonary rehabilitation with 18 µg of tiotropium once daily (tiotropium group). The patients in the tiotropium group received tiotropium for more than 1 week before surgery and for 2 weeks after surgery. Spirometry was performed prior to group assignment and at 2 weeks after surgery. Postoperative complications, forced expiratory volume in 1 second, forced vital capacity, and the ratio of forced expiratory volume in second to forced vital capacity (%) were compared between the two groups. RESULTS: There were no significant differences between the two groups in terms of age, body mass index, smoking, gastrectomy incision, operation time, and bleeding volume (all P>0.05). Postoperative complications and pulmonary functions did not differ significantly between the control and tiotropium groups. A subgroup analysis of gastric cancer patients with moderate COPD showed that perioperative tiotropium intervention significantly decreased the rate of postoperative complications compared with the control group (P=0.046). However, even after gastrectomy, many patients with mild COPD in both the control and tiotropium groups showed improved pulmonary function. CONCLUSION: Although perioperative tiotropium intervention had no significant effects in gastric cancer patients with mild COPD, it may be beneficial in those with moderate COPD. Therefore, the next prospective study should further evaluate perioperative tiotropium intervention for gastric cancer patients with moderate-to-severe COPD.

Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer.

The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX) has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC) inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy.

[Poor outcome of a patient with early double cancers of the stomach and sigmoid colon in which liver metastases were detected postoperatively].

A 63-year-old man underwent laparoscopic-assisted distal gastrectomy (LADG) and laparoscopic assisted colectomy (LAC) simultaneously for double cancers of the gastric antrum and sigmoid colon in August 2012. Both cancers, considered to be at an early-Stage, were pathologically diagnosed as tub1, sm, and n0. The patient was observed but no adjuvant chemotherapy was administered. A follow-up computed tomography (CT) in December 2012 detected a 15 mm tumor mass in the lateral segment of the liver and another 5mm mass in the S4. Liver metastasis of the sigmoid colon cancer was suspected, and 6 courses of BEV+mFOLFOX6 were administered. The metastatic tumor in the lateral segment showed stable disease (SD) and the S4 tumor showed a complete response (CR). Thereafter, the lateral hepatic segment was partially resected in March 2013. Pathological examinations led to a diagnosis of stomach cancer liver metastasis, and the patient was given oral TS-1. During the first course of treatment, a CT showed new tumor masses in the lateral segment of the liver and S4. Treatment was changed to TS-1+CDDP in mid-May. However, after completion of the first course of treatment, the patient experienced exacerbation of the liver metastases, pulmonary metastasis, and inflammation of the intrahepatic bile ducts. The patient was hospitalized in mid-June to receive inpatient care, but died in early July.