Phase II study of S-1 monotherapy in patients over 75 years of age with advanced gastric cancer (OGSG0404).

BACKGROUND: S-1+cisplatin (CDDP) is the standard treatment for advanced gastric cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based chemotherapy for elderly patients is unclear. Therefore, we conducted a multicenter phase II study of S-1 monotherapy for AGC in elderly patients. MATERIALS AND METHODS: Chemotherapy-naïve patients aged over 75 years with AGC were enrolled. The starting dose of S-1 was determined on the basis of body surface area and modified according to the creatinine clearance value. S-1 was administered twice a day during a 4-week period followed by a 2-week rest period. RESULTS: Thirty-five patients were enrolled. The response rate (RR) was 14.3% and the median overall survival was 14.6 months. Grade 3 or more severe adverse events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue (6%). There were no treatment-related deaths. CONCLUSION: Our study indicates that S-1 monotherapy is safe and well tolerated in chemotherapy-naïve elderly patients with AGC, but exerts limited activity when given using a tailor-made dosing strategy based on renal function.

[Feasibility and outcome of S-1 adjuvant chemotherapy for patients with gastric cancer treated based on the liaison-clinical pathway].

We retrospectively examined the feasibility and outcome of S-1 adjuvant chemotherapy for 18 patients with gastric cancer treated based on the liaison-clinical pathway (liaison group), and compared them with those of 26 patients treated before the induction of the liaison-clinical pathway (non-liaison group). The persistent rate of S-1 adjuvant chemotherapy for one year except for recurrence, the relative performance (RP) value of cases who had received S-1 for one year, and Grade 3/4 adverse events in non-liaison group/liaison group, were 88.5/87.5% (p = 0.93), 87.0/92.9% (p = 0.56), and 26.9/5.6% (p = 0.07), respectively. This did not show a significant difference. The rate of patients administered medication for coexistent diseases in our hospital in the non-liaison group/liaison group was 53.8/0% (p = 0.0002), which reflected the accomplishment of the transfer of medical care for coexistent disease from a hospital to a clinic on the liaison-clinical pathway. Furthermore, a neighboring clinic could be arranged to accommodate 9 (64.3%) of 14 patients living quite far from the hospital in the liaison group. In conclusion, S-1 adjuvant chemotherapy for patients with gastric cancer treated based on the liaison-clinical pathway was feasible, led to the effective practice of sharing between hospital and clinic, and the shorter trip for treatment at a neighboring clinic by patients living far from a hospital.

[A case report of locally recurrent rectal cancer after low anterior resection that led to a pathological complete response to neoadjuvant chemoradiotherapy].

We report a case of low anterior resection that led to a pathological complete response of locally recurrent rectal cancer to neoadjuvant chemoradiotherapy. A 57-year-old male patient underwent low anterior resection for rectal cancer pathologically diagnosed as type 2, tub2>tub1,pSS,INF b,int,ly2,v2,pPM0,pDM0,no,M0,H0,P0, and fStage II. After 2 years and 11 months, local recurrence of his rectal cancer was identified by colon fiberscopy. Neoadjuvant chemoradiotherapy was conducted with CPT-11, UFT/LV, and radiation(50 Gy),and this recurrent lesion exhibited a partial response to the chemoradiotherapy regimen according to magnetic resonance imaging findings. Then, we performed total pelvic exenteration, and the pathological examination revealed a pathological complete response.

[The feasibility of CDDP administration for gastric cancer outpatients undergoing S-1/cisplatin combination therapy].

UNLABELLED: S-1/cisplatin(CDDP) combination therapy(SP therapy)(S-1: 80 mg/m2/day, day 1-21, CDDP: 60 mg/m2, day 8, q35 days) is a standard regimen for advanced gastric cancer in Japan. Hydration under hospitalization is necessary for CDDP administration to prevent renal toxicity; nevertheless, ambulatory chemotherapy has recently become commonly used. Therefore CDDP administration using a short hydration regimen for gastric cancer outpatients undergoing SP therapy has been performed in our institute. Between August 2009 and November 2011, 23 patients who were treated with SP therapy as a first line therapy and began CDDP treatment in the outpatient setting were examined, and monitored for adverse events, response rate[best objective response rate(ORR)], time to treatment failure(TTF) and overall survival. A short hydration regimen means 2,550 mL of fluid in 4 h and 55 min, and the necessity of an oral intake of more than 1,000 mL liquid per day on day 7 to 9 was explained to the patients. Grade 1/2 serum creatinine elevation occurred in 5 patients (22%), but there were no incidences of grade 3/4 serum creatinine elevation or heart failure. The best ORR was 69%, median time to treatment failure(mTTF) was 11.5 months, the 1-year survival rate was 77.8%, and the 2-year survival rate was 44.7%. CONCLUSION: CDDP administration using a short hydration regimen for gastric cancer outpatients undergoing SP therapy was considered to be feasible.

[A case of refractory deep incisional surgical site infection due to methicillin-resistant Staphylococcus aureus (MRSA) and successfully treated with oral linezolid].

We report a case of methicillin-resistant Staphylococcus aureus(MRSA) surgical site infection successfully treated with linezolid. A 66-year-old man had undergone total gastrectomy for gastric cancer after neoadjuvant chemotherapy. Three days after the operation, he was diagnosed with deep incisional surgical site infection due to MRSA, and wound care was started. After discharge, he received adjuvant chemotherapy and wound care, but the wound had not healed in 10 months. We started treatment with oral linezolid and nutritional support, and the wound was fully healed 12 months after the operation. Antibiotic treatment with oral linezolid may be effective for refractory deep incisional surgical site infection due to MRSA in outpatients.

[Examination of factors influencing continuity of S-1 adjuvant chemotherapy for gastric cancer patients].

After Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC), adjuvant chemotherapy with S-1 is a standard treatment for stage II or III gastric cancer patients. In this study, we retrospectively examined factors that influence the continuity of S-1 adjuvant chemotherapy. We analyzed the clinical documentation of 27 gastric cancer patients being treated with S-1 adjuvant chemotherapy. Patients who completed the treatment without reduction dose were classified into a complete group(n=14), and those for whom S-1 was discontinued or reduced due to adverse reactions were classified into a reduced/discontinuation group(n=13). First, we examined the background factors at baseline between these two groups. Univariate logistic regression analysis revealed that the operative procedure, leukocyte count, and serum creatinine level at baseline were identified as factors that influence the continuity of S-1 chemotherapy. Next, we investigated the hematological and nutritional conditions of these patients during the treatment period. The loss of body mass index(BMI)during the treatment period was remarkable in the reduced/discontinuation group regardless of the operative procedure. This result suggests that an early nutritional intervention might be important for gastric cancer patients undergoing S-1 adjuvant chemotherapy.

[Gastrojejunostomy followed by chemotherapy with S-1 in unresectable gastric cancer with pyloric stenosis].

We investigated the efficacy of gastrojejunostomy followed by S-1-based chemotherapy for unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy and S-1-based chemotherapy in 14 unresectable gastric cancer patients with gastric outlet obstructions between April 2006 and June 2010. Although there were two complications after surgery, no treatment-related deaths were observed. The response rate of the S-1-based chemotherapy was 41.7%, and the median survival after surgery was 12.3 months. All patients were tolerating a regular diet and a significant improvement in oral intake lasted for at least 6 months. In conclusion, gastrojejunostomy followed by chemotherapy with S-1 appears to be an effective treatment modality for unresectable gastric cancer with pyloric stenosis. It enables us to practice S-1-based standard chemotherapy for advanced gastric cancer and improve the quality of life of patients.

[Evaluation of the S-1 granule forms in gastric cancer patients who received treatment with S-1 capsule-questionnaire survey about drug dosage forms].

The S-1(tegafur/gimeracil/oteracil potassium)granule was developed to meet the needs of patients with cancer. Although the choice of the patients was thought to spread by the addition of the new agent type, the recognition of the S-1 granule is still low and you should adapt yourself to what kind of patients or are unknown. Therefore, we conducted a questionnaire survey of patients with gastric cancer undergoing treatment with S-1 capsules to investigate the adaptation and taste of the patients. As a result, although it was the investigation by the patients during S-1 capsule remedy, it was replied when 21. 3%(13/61 case)'had good granule,'and all cases raised it by the reason of there'not being the sense of incongruity of the throat at taking.'Also, about the global assessment of granule, the proportion of patient who replied'very good'or'good'were 31. 1% and 47%, in all cases and in the cases that felt the sense of incongruity of the throat during S-1 capsule remedy, respectively. Therefore, in the patients treated with the S-1 capsule, there were thought to be the patients who expected treatment with a granule. By the results of this survey, it was found that it is necessary to perform a medical teaching including dosage form to contribute to the adherence improvement of the patients.

[A case report of scirrhous gastric carcinoma diagnosed by staging laparoscopy].

The case is a sixty-something man with a complication of epigastric abdominal pain. X-ray and endoscopic examination of upper gastrointestinal tract showed a rigidity of the gastric wall and the presence of giant folds on gastric body and fornix. Scirrhous type of gastric cancer was suspected and gastric forceps biopsy was performed at many points under the retreated endoscopic examinations. However, the histologic findings revealed no malignant features. We performed staging laparoscopy, and by peritoneal washing cytology and biopsy of a nodule of abdominal wall, he was diagnosed with advanced gastric carcinoma with peritoneal dissemination. In conclusion, staging laparoscopy is one of the useful methods for diagnosis and determination of the management of scirrhous type gastric carcinoma.

[A case of malignant melanoma of the esophagus].

A 56-year-old female with chest pain after a meal was found to have the black mucous membrane of the middle intrathoracic esophagus by esophagogastroduodenoscopy. The lesion was diagnosed as primary malignant esophageal melanoma without lymph nodes and other organ metastasis. We underwent a subtotal esophageal by right thoracotomy and laparotomy. She survives with relapse-free for 3 years after the surgery. There is no standard therapy because primary malignant esophageal melanoma is not common. However, we thought a surgical treatment should be performed for a curatively resectable case.

[Examination of continuity of S-1 adjuvant chemotherapy for gastric cancer patients after gastrectomy].

Next to ACTS-GC (Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer), adjuvant chemotherapy with S-1 is the standard treatment for stage II or III gastric cancer patients.In this study, we retrospectively examined the continuity and adverse reaction of S-1 adjuvant chemotherapy in 30 gastric cancer patients who visited our hospital from 2007 to 2008, and compared them with those of patients treated with ACTS-GC. Whereas the persistent rate of S-1 adjuvant chemotherapy for one year in ACTS-GC was 65.8%, it was 86.7% in our hospital.The RP (Relative performance) value in cases who completed S-1 adjuvant therapy for one year in ACTS-GC and for one year in our hospital was 81.2% and 88.5%, respectively. Grade 3/4 adverse events in our hospital were leukopenia (3.3%), neutropenia (16.7%), and anorexia(6.7%). In conclusion, our hospital has shown a far greater continuity with S- 1 adjuvant chemotherapy than with ACTS-GC, a result suggesting that S-1 adjuvant chemotherapy is feasible in clinical practice.

Usefulness of staging laparoscopy for advanced gastric cancer.

PURPOSE: The aim of this study was to clarify the usefulness of staging laparoscopy for planning the treatment strategy in patients with advanced gastric cancer. METHODS: This was a retrospective study of patients with gastric cancer who underwent staging laparoscopy. The patients were divided into three groups according to the presence/absence of peritoneal metastasis (P) and positive peritoneal cytology (CY): P negative (0) CY0, P0CY positive (1), and P1CY1. The treatment strategy after staging laparoscopy was as follows: (1) surgery for the P0CY0 group, (2) surgery with neoadjuvant chemotherapy (NAC) for the P0CY1 group, and (3) chemotherapy for the P1CY1 group. Survival was estimated by the Kaplan-Meier method and statistical differences were analyzed by the log-rank test. RESULTS: Thirty-four patients were included in this study: 11 in the P0CY0 group, 13 in the P0CY1 group, and 10 in the P1CY1 group. A gastrectomy was done in 11, 10, and no patients, respectively. The survival rate of the P0CY0 patients was significantly better than that of the P0CY1 or P1CY1 patients (P = 0.0106 and 0.0031, respectively). CONCLUSION: Staging laparoscopy is useful for planning the treatment strategy and estimating the prognosis of patients with advanced gastric cancer.

[A case with anastomotic stricture after total gastrectomy that was successfully treated with argon plasma coagulation].

A 73-year-old man admitted for anastomotic stricture not treated successfully with balloon dilation after proximal gastrectomy and fund plication in February 2009. Total gastrectomy and esophagojejunal anastomosis with mechanical stapler were performed. Dysphagia occurred after the operation and slack of jejunum mucosa directly under esophagojejunal anastomosis was observed with endoscope. Anastomotic stricture was not successfully treated with endoscopic balloon dilation. Therefore, APC was performed for slack of jejunum mucosa. As a result, anastomotic stricture was treated and had not reappeared until 1 year and 2 months later after APC. APC was safe and effective for anastomotic stricture of esophagojejunal anastomosis with mechanical stapler due to slack of jejunum mucosa.

[Case report of internal hernia after surgery for gastric cancer].

We report rare cases of internal hernia after surgery for gastric cancer. Four patients who had undergone gastrectomy (Roux-en Y reconstruction) for gastric cancer were admitted to our hospital after onset of abdominal pain or vomiting. Abdominal X-ray revealed small intestine gas and niveau, and abdominal CT scan showed the whirl sign in all cases. We diagnosed internal hernia and performed surgery. In 3 cases, small intestine was strangulated through the space between the mesentery of the Roux-Limb and transverse mesocolon, and in one case, it was strangulated through the space between the mesentery of the Roux-Limb and the mesentery of afferent loop. We reversed the ileal strangulation and closed the hernia orifice.

[A case of gastric cancer with bilateral ovarian metastasis after gastrectomy performed ovarian resection].

The patient was a 51-year-old female, who underwent radical surgery for cancer of remnant stomach in May 2006 (f-T4N0M0P0H0CY0, por 2, Stage IIIA, Cur B). Bilateral ovarian resection was performed in March 2009 for bilateral ovarian metastasis, so called "Krukenberg tumor" with peritoneal dissemination detected with CT scan after one-year adjuvant chemotherapy with S-1 (80 mg/m2, 4 weeks on and 2 weeks off). As of June 2010, she is alive and maintain her status quo after 6 courses of S-1 plus CDDP combination therapy (S-1 80 mg/m2, 3 weeks on, CDDP 60 mg/m2, started at day 8, ended 35 days later) followed by S-1 for residual peritoneal dissemination detected at operation. In ovary metastasis of gastric cancer, even if accompanied by peritoneum metastasis, ovarian resection as a reduction surgery followed by chemotherapy may improve survival.

[Three scirrhous gastric cancer cases with CY negativity in second-look staging laparoscopy after chemotherapy to whom curative surgery was carried out].

Case 1: A 77-year-old female with scirrhous gastric cancer was diagnosed as c4T3N1H0M0P0CY1/stage IV, and S-1/docetaxel combined therapy was carried out. The wall thickness of stomach improved after 11 courses. Case 2: A 48-year-old female with scirrhous gastric cancer was diagnosed as c4T3N1H0M0P0CY1/stage IV, and S-1/CDDP/paclitaxel combined therapy was carried out. The wall thickness of stomach improved after 5 courses. Case 3: A 37-year-old man with scirrhous gastric cancer was diagnosed as c4T3N0H0M0P1CY1/stage IV, and S-1/CDDP/paclitaxel combined therapy was carried out. The wall thickness of stomach improved after 5 courses. In all cases, CY and P negativity was confirmed in second-look staging laparoscopy and curative surgery was carried out.

[Three patients successfully treated with orthopedic surgery for spinal paralysis due to spine metastasis of gastric cancer].

We report three patients who were successfully treated with orthopedic surgery for spinal paralysis due to spine metastasis of gastric cancer. Case 1: A 75-year-old female had lower limb paralysis due to metastasis of Th1-Th3 one year and four months after total gastrectomy for gastric cancer. Although radiotherapy was carried out from the day following a paralysis appearance, the paralysis deteriorated from D to C. Then, when direct decompressive surgical resection had been performed eight days after the paralysis appearance, the paralysis improved from C to D. Case 2: A 50-year-old male had lower limb paralysis due to metastasis of Th2 three years and eight months after distal gastrectomy for gastric cancer. Paralysis had improved from C to D with direct decompressive surgical resection three days after the paralysis appearance and radiotherapy after surgery. Case 3: An 80-year-old male had lower limb paralysis due to metastasis of Th3 five years and eight months after total gastrectomy for gastric cancer. Paralysis had improved from B of a Frankel classification to C with direct decompressive surgical resection seven hours after the paralysis appearance and radiotherapy after surgery. When the spinal paralysis due to spine metastasis of gastric cancer appeared, the orthopedic surgery for QOL maintenance was considered to be one of the useful medical treatment options.

[A case of paclitaxel-induced peripheral neuropathy successfully treated by H2-blocker, lafutidine].

We report a 75-year-old female gastric cancer patient with paclitaxel-induced peripheral neuropathy, which was successfully treated by the H2-blocker, lafutidine. From December 2007, she underwent second-line chemotherapy using paclitaxel (80 mg/m/2 day 1, 7, 14/28 days) for peritoneal dissemination which had been refractory to first-line chemotherapy using S-1 (80 mg/m / 2, day 1-28/42 days). After 2 courses, CT showed a complete response (CR) of the peritoneal dissemination. However, at the same time peripheral neuropathy appeared, which was aggravated to grade 3 at the 6th course. Beginning with the 7th course, we administered lafutidine (10 mg/day) for peripheral neuropathy, which recovered to grade 1 after 14 days of lafutidine administration. Lafutidine was administered until July 2008, when peripheral neuropathy kept grade 1 without lafutidine. After 9 courses, paclitaxel therapy failed because of general fatigue.