Phase II study of S-1 as first-line treatment for elderly patients over 75 years of age with advanced gastric cancer: the Tokyo Cooperative Oncology Group study.

PURPOSE: This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer. METHODS: Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25-60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses. RESULTS: Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7-37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes. CONCLUSIONS: The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

[A case report of complete response by S-1/docetaxel combination chemotherapy for advanced gastric cancer].

A 52-year-old male patient with advanced gastric cancer and multiple lymph node metastasis was treated by S-1/docetaxel combination chemotherapy from April, 2004. As of January 2005, after the tenth course, a scarred tumor was observed with an endoscope, and negative neoplastic cells were found on endoscopic biopsy. After the sixteenth course in July, 2005, CT scan showed that the lymph node metastasis had disappeared. The primary and metastatic lesions were regarded to have responded completely. A total of 26 courses of chemotherapies were undergone until March, 2006. We are taking a wait and see approach at this writing without treatment since then. The patient has had a recurrence-free survival for about five years since the onset. The results suggested that the S-1/docetaxel chemotherapy for metastatic gastric cancer had confirmed feasibility and sufficient efficacy while maintaining the patient's quality of life.

Second-line chemotherapy with biweekly paclitaxel after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer: a report from the gastrointestinal oncology group of the Tokyo cooperative oncology group, TCOG GC-0501 trial.

OBJECTIVE: A multicenter trial was conducted to evaluate the efficacy and safety of paclitaxel every 2 weeks in patients with advanced or recurrent gastric cancer who had previously received fluoropyrimidine-based chemotherapy. METHODS: The subjects were patients with gastric cancer who had disease progression or recurrence while receiving fluoropyrimidine-based chemotherapy. All patients had adequate major organ functions with an Eastern Cooperative Oncology Group performance status (PS) of 0-2. Paclitaxel 140 mg/m(2) was administered intravenously on days 1 and 15 of a 4-week cycle. The primary endpoint was the response rate. Secondary endpoints were progression-free survival (PFS), overall survival and safety. RESULTS: Response was assessable in 40 of 41 enrolled patients. Their median age was 63 (range: 48-77) years, and PS was 0 in 22 patients, 1 in 13 and 2 in 5. Previous treatment included S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) monotherapy in 32 patients and S-1-based combination therapy in 5. The median number of administered courses of paclitaxel was 3.5 (1-14). The response rate was 17.5% (95% confidence interval: 7.3-32.8%, partial response: 7, stable disease: 21, progressive disease: 10 and not evaluable: 2). The disease control rate was 70.0%, the median PFS was 111 days and the median overall survival was 254 days. Major adverse events of Grade 3 or 4 were neutropenia (27.5%), anemia (12.5%), diarrhea (2.5%) and sensory neuropathy (2.5%). CONCLUSIONS: Biweekly paclitaxel seemed to be one of the useful chemotherapies after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer.

S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial.

BACKGROUND: Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone. METHODS: In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670. FINDINGS: 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.9]) than in those assigned to S-1 alone (11.0 months [5.6-19.8]; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.9] vs 4.0 months [2.1-6.8]; p<0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group. INTERPRETATION: S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer.

Randomized phase II study comparing mitomycin, cisplatin plus doxifluridine with cisplatin plus doxifluridine in advanced unresectable gastric cancer.

UNLABELLED: Various chemotherapies have been used to treat inoperable gastric cancer. Most combination therapies include cisplatin (CDDP) and fluoropyrimidine (5-FUs), which are thought of as key drugs. In the present study, we randomly compared mitomycin (MMC) and CDDP plus doxifluridine (5'-DFUR), which is an oral 5-FU and an intermediate metabolite of capecitabine (Xeloda), with CDDP plus 5'-DFUR in advanced unresectable gastric cancer. Regimen A was CDDP (70 mg/m2, by 2-hour intravenous drip infusion on day 1), MMC (7 mg/m2, injected intravenously on day 2), and oral 5'-DFUR (1200 mg/m2, on days 4 to 7, 11 to 14, 18 to 21 and 25 to 28; 3 days rest and 4 days administration). Regimen B was identical to regimen A without MMC. RESULTS: The response rate was 25.0% (8/32 patients) in Regimen A, 17.2% (5/29) in Regimen B (p=0.541). The median survival time was 241 days in Regimen A and 179 days in Regimen B (p=0.498). In Regimen A, although no significant difference was observed, end points such as response rate and suvival improved. Thus, we concluded that a randomized controlled phase III study with more subjects should be conducted.

Role of Endosonography in Diagnosis of Esophageal Bronchogenic Cyst: -Report of Two Cases.

Bronchogenic cyst is very difficult to diagnose preoperatively. We report two cases of bronchogenic cyst of the esophagus diagnosed and treated by thoracoscopic resection or endoscopic mucosal incision. Thoracoscopic resection was performed to diagnose and treat case 1, while in case 2, histological diagnosis was obtained with an endoscopic mucosal incision. On endoscopic ultrasonography, the lesion characteristically demonstrated two components consisting of an anechoic and homogeneous echoic pattern. Although it is very rare for bronchogenic cyst to be complicated by malignancy, histological diagnosis is necessary. If tumor localization is in the esophageal wall and the safety of a mucosal incision can be confirmed, endoscopic incision is a good alternative that allows less invasive diagnosis and treatment than surgery or thoracoscopy.