A case of complete response (CR) persisting for 2 years from S-1 administered five days a week in a patient with gastric cancer

We attempted S-1 administered five days a week from March, 2004 for an 84-year-old female harboring Borrmann type 1 gastric cancer because her family did not agree to her gastrectomy. After treatment for 1 month the lesion changed into a shallow ulcer. The lesion was clinically diagnosed with CR about 3 months later. As of October, 2006, 2 years after inducing CR, we have been administering S-1 to the patient, with no regrowth of the tumor.     

Report of two cases successfully treated by chemo-radiation against lymph node metastasis after gastric cancer surgery

A 68-year-old male patient with mediastinal node metastasis 40 months after total gastrectomy for advanced gastric cancer, and a 72-year-old male patient with para aortic node metastasis were treated with concurrent chemo-radiotherapy of 1.8 Gy × 5 × 6 week with S-1 (100 mg/body, days 1-14 and 22-35) + docetaxel (30 mg/body, days 1, 8, 22, 29). Although two patients developed a lymph node recurrence during multiple chemotherapies including S-1, they have responded well and demonstrated complete response after chemo-radio therapy. Grade 3 esophagitis was sole adverse side effect. In contrast to the western countries, chemo-radio therapy was not recognized as a standard treatment for gastric cancer in Japan. However, our report suggested that chemo-radio therapy can be an option for the treatment of advanced gastric cancer.     

A case of recurrent gastric cancer successfully treated with S-1 plus CDDP (divided into small dosages)

A 75-year-old man was found to have a type 2 gastric cancer on the pyloric side. In February 2006, he underwent gastrectomy, followed by oral medication with 300 mg/day of UFT on an ambulatory basis. In June 2006, the lymph nodes in the hepatoduodenal ligament became swollen. The patient was started on S-1 monotherapy(S-1 was given orally 80 mg/body/ day for the first 4 weeks of a 6 week cycle). S-1 was given for 6 courses over 9 months. In March 2007, further swelling of the lymph nodes in the hepatoduodenal ligament(PD)and a CEA level increase were noted, and therapy of S-1 combined with CDDP(divided into small dosages)was started in April 2007. Since then until July 2009, 16 courses of S-1 combined with CDDP therapy were completed. During this period(for 2 years and 3 months), the lymph nodes in the hepatoduodenal ligament remained generally unchanged(SD)in imaging observations. However, no new lesions were discovered, The CEA level was reduced and the patient remained free of clinical symptoms. While there are no adverse effects and he could receive continued care on an ambulatory basis. In September 2009, obstructive jaundice was found, and it was treated by biliary stenting. He suffered repeated bouts of cholangitis, which contributed to the exacerbation of his systemic condition. The patient succumbed in January 2010. S-1 monotherapy was found to be ineffective but a combination therapy of S-1 plus CDDP(divided into small dosages)was effective in dealing with a recurrence of the gastric cancer. A case was presented in which such treatment allowed a patient with recurrent gastric cancer to survive for 3 years and 11 months following surgery.     

Complete response achieved following administration of S-1 in a patient with adrenal gland metastasis of 5-FU-resistant gastric cancer: a case report.

A 62-year -old male patient who had undergone total extirpation of type 3 cancer of the greater curvature of the upper stomach body at another hospital received postoperative chemotherapy with 5-FU and methotrexate. The patient was subsequently treated with oral 5-FU. About 1 year later, a 4 cm tumor of the left adrenal gland was revealed by abdominal CT and diagnosed as gastric cancer metastasizing to the adrenal gland. The patient was referred to our hospital for close examination and treatment and admitted. After his informed consent had been obtained, the patient received one course (4-week administration and 2-week withdrawal) of S-1 at 50 mg/body x 2/day. Abdominal computed tomography performed after the end of the one course revealed that the tumor had become undetectable. This condition was still maintained at the end of two courses and judged to be complete response (CR) (in accordance with the WHO Efficacy Judgment Criteria). CR has continued to be maintained to the present time, even after seven courses. There has been no previous report of S-1 showing remarkable effectiveness in a patient with 5-FU-resistant gastric cancer metastasizing to the adrenal gland. We consider that the efficacy of S-1 for treatment of 5-FU-resistant gastric cancer should be verified.     

Therapeutic strategy for type 4 gastric cancer from the clinical oncologist standpoint

Type 4 gastric cancer has a poor prognosis compared with other types of advanced gastric cancer because of the high incidence of peritoneal metastasis which causes intestinal obstruction, hydronephrosis, or obstructive jaundice. Surgical treatment is often only palliative, and systematic chemotherapy is considered to be important for long survival. S-1 showed a higher response rate for undifferentiated-type adenocarcinoma, and S-1 alone or its combination regimens demonstrated greater anti-tumor effects and longer survival time for gastric linitis plastica compared with conventional 5-FU regimens in our historical control study (response rate: S-1/non S-1 57.9%/27.9%, p<0.01; MST: S-1/non S-1 402 days/213 days, p<0.01). S-1 regimens may also improve the survival in patients with type 4 gastric cancer in neoadjuvant or adjuvant settings, but further prospective studies are warranted to prove its significance. Paclitaxel also has a high response rate for undifferentiated-type adenocarcinoma, and can be expected to show high efficacy for peritoneal dissemination. Irinotecan should not be administered in case of intestinal obstruction because its toxicity may be increased. However,survival of patients with type 4 gastric cancer may improve with the availability of active agents like S-1, taxanes, irinotecan as reported in colorectal cancer. Therefore,irinotecan should be administered carefully before intestinal obstruction occurs.     

A case of advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy using CPT-11 plus S-1

Adjuvant chemotherapy for advanced gastric cancer has not yet been established. We report a patient with advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy consisting of CPT-11 and S-1. The patient was a 69-year-old woman diagnosed with large type 3 advanced gastric cancer with esophageal invasion and having No.3 lymph node metastasis (cT3, cN1, cM0, cStage IIIA), treated with 2 courses of CPT-11 plus S-1 as neo-adjuvant chemotherapy. Computed tomography after neo-adjuvant chemotherapy showed improvement of gastric wall thickness and reduction of lymph node metastasis. Subsequently, she underwent an operation. There was no lymph node swelling,so we performed curative surgery consisting of total gastrectomy, splenectomy, cholecystectomy, and D 2 lymph node dissection. Histological diagnosis was pT2 (MP), pN1, pStage II, and estimation of the histological change by chemotherapy was Grade 2. The course after surgery was good, and she was treated by S-1 after discharge. To date, 8 months after surgery, there is no evidence of recurrence. Combination chemotherapy consisting of CPT-11 plus S-1 can be performed safely as a neo-adjuvant treatment, and may be an effective treatment modality for advanced gastric cancer.     

A case of multiple bone metastases from gastric cancer treated with combination chemotherapy of S-1 and CDDP

We report a case of multiple bone metastases from gastric cancer treated with combination chemotherapy of S-1 and CDDP. A 54-year-old man underwent distal gastrectomy for gastric cancer (Stage II) in March 2003. Multiple bone metastases complicated with DIC were diagnosed in September 2005. The patient was treated with combination chemotherapy of S-1 and CDDP. S-1 (80 mg/m2/day) was administered for 21 days followed by 14 days rest as one course. CDDP (60 mg/m2) administration was begun 8 days after the start of S-1. After one course of the treatment, DIC was resolved. The abnormal uptake at the bone metastases was found to have decreased by bone scintigraphy. Bone metastases recurred in April 2006. Although combination chemotherapy of S-1 and DOC was administered, the patient died of DIC in August 2006. Combination chemotherapy of S-1 and CDDP is considered effective treatment for prolonging survival in cases of gastric cancer with bone metastases.     

A case of liver metastasis of gastric cancer undergoing non-curative operation responding completely to combination therapy of S-1 and CDDP

We experienced a case with liver metastasis of gastric cancer that disappeared by S-1 administration following non-curative operation. A distal gastrectomy for advanced gastric cancer with liver metastasis was performed on a 71-year-old male. S-1 was administered at 100 mg/body/day for 4 weeks followed by withdrawal for 2 weeks, and CDDP was prescribed at 5 mg/body/day div, for 2 days per a week as 1 course. After one course of treatment, the liver metastatic lesion decreased in size (reduction ratio was 87.4%). For side effect, S-1 100 mg alone was administered beginning with the second course. This lesion became CR after four courses. The adverse events of grade 3 observed during S-1 administration were neutropenia and diarrhea. We changed S-1 to UFT after nine courses, and the patient has now survived 1 year without recurrence after the disappearance of liver metastasis.     

A case of AFP-producing gastric cancer with hepatic metastases that accompanied early gastric cancer treated effectively by chemotherapy

We report a case of alphafetoprotein (AFP)-producing gastric cancer that accompanied early gastric cancer and was treated effectively by chemotherapy. The patient was a 73-year-old male. A type 1 tumor was observed in the upper gastric body and a 0-IIa tumor was noted on the anterior wall of the lower gastric body. Abdominal CT showed multiple metastatic lesions in the liver. A subtotal gastrectomy was performed, and the pathological examination revealed that the type 1 tumor was positive for AFP and the 0-IIa tumor was negative for AFP. After 5 courses of postoperative administration of S-1, hepatic metastatic lesions disappeared on imaging. The serum AFP level, which had increased to the maximum of 49,660 ng/ml, was normalized. After 60 months, there has been no sign of recurrence. We encountered a case of AFP-producing gastric cancer that accompanied early gastric cancer and was treated effectively by S-1. Various therapies for AFP-producing gastric cancer have been reported; however, a standardized regimen has not been established. Since the concurrence of AFP-producing gastric cancer and tubular adenocarcinoma is rare, and hepatic metastatic lesions disappeared, the case under study is considered to be of interest. Therefore, we report this case with a review of the literature.     

S-1-induced, prolonged complete regression of lung metastasis from gastric cancer refractory to 5'-DFUR: a case report with pharmacokinetic study

S-1 is an oral fluoropyrimidine reported to be most active for gastric cancer. However, few studies have documented a complete response (CR) of lung metastasis to S-1 treatment. We describe a 66-year-old woman in whom S-1 induced complete regression of lung metastasis from gastric cancer, that had been refractory to another oral fluoropyrimidine, 5'-deoxy-5-fluorouridine (5'-DFUR). After preoperative chemotherapy with a combination of etoposide, adriamycin and cisplatin and with methotrexate plus 5-fluorouracil, the patient underwent a total gastrectomy with lower esophagectomy for advanced diffuse-type gastric cancer with invasion of the esophagus in May 1993. She received postoperative adjuvant chemotherapy with 5'-DFUR (600 mg/day) for 3 years. However, a solitary metastasis to the left lung was detected in November 1996 and she underwent partial resection of the left lung. Chemotherapy with 5'-DFUR was reinitiated after operation, but re-metastasis to the left lung with elevation of the serum carcinoembryonic antigen (CEA) level was diagnosed in June 1999. Treatment with S-1 was started in August. S-1 was given orally in a dose of 100 mg/day for 28 consecutive days, followed by a 14-day recovery; treatment was repeated every 6 weeks. The metastatic lesion in the left lung completely regressed after two courses of S-1 and the serum CEA level returned to the normal range. The patient received a total of 10 courses of S-1. The dose of S-1 was reduced to 80 mg/day from the sixth course because of grade 2 skin rash. Pharmacokinetic studies after administration of S-1 revealed high and prolonged plasma 5-FU levels. Nearly 4 years have passed since complete regression of the lung metastasis. This may be the first report to document a prolonged complete response of lung metastasis from gastric cancer induced by single-agent chemotherapy with S-1.     

A case of advanced gastric cancer with pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases responding to combination chemotherapy of S-1 and irinotecan(CPT-11)

A 70-year-old woman with pulmonary carcinomatous lymphangitis and paraaortic lymphnode metastases due to gastric cancer, was treated by combination chemotherapy of S-1 and irinotecan(CPT-11). After one course of the chemotherapy, pulmonary carcinomatous lymphangitis and paraaortic lymphnode metastases were remarkably improved. Diet intake was improving and cancer pain remarkably declined. Because the origin of gastric cancer was not improved, total gastrectomy, distal pancreatectomy and splenectomy were performed. After surgery, relapse of pulmonary carcinomatous lymphangitis caused death of the patient. The combination chemotherapy of S-1 and CPT-11 was effective for pulmonary carcinomatous lymphangitis and paraaortic lymphnodes metastases due to gastric cancer. However, careful consideration is required since surgery is performed on a patient who had suffered pulmonary carcinomatous lymphangitis.     

Intraperitoneal administration of paclitaxel and oral S-1 for a patient with peritoneal dissemination and hydronephrosis due to advanced gastric cancer

We report a patient with type 3 gastric cancer with peritoneal dissemination and hydronephrosis who was successfully treated with intraperitoneal infusion of paclitaxel and oral administration of S-1. He was diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m² was administered intraperitoneally on days 1 and 8, and S-1 at 100 mg/body was administered orally for 14 days, followed by 7 days’ rest, as one course. After five courses, primary tumor reduction was confirmed and no cancer cells were detected on pathocytological investigation at second-look laparoscopy. The patient underwent total gastrectomy with lymph node dissection. He died from liver metastasis 29 months after the initial treatment, but he had not suffered from peritoneal metastases and had kept a good quality of life (QOL) since that treatment. This chemotherapy can be applied as one of the promising candidates for the treatment of patients with peritoneal metastasis of gastric cancer.     

Pathological complete response in an elderly patient with locally advanced gastric cancer treated with S-1/CDDP

We report a patient with locally advanced gastric carcinoma successfully treated with S-1/CDDP. The patient was a 77-year-old woman who had gastric cancer surgically diagnosed as T4N2, invading the pancreas and mesocolon. After the firsts exploratory laparotomy, chemotherapy was begun as follows. S-1(80 mg/day)was orally administered for 3 weeks followed by 2 weeks' rest as a course, and CDDP(75 mg/body)was administered by intravenous drip on day 8. Because of severe anorexia and nausea, however, the CDDP administration had to be discontinued. Therefore, we changed the procedure to S-1 single treatments, 2 weeks' administration followed by 2 weeks' rest. The total 9 courses of this procedure proved successful. Subsequently, she underwent curative surgery consisting of total gastrectomy with D2 lymph node dissection, combined with distal pancreatectomy and splenectomy, and obtained pathological CR. S-1/CDDP appears to be an effective treatment modality for advanced gastric cancer.     

An effective treatment by chemotherapy with S-1 and CDDP intraperitoneal administration for the peritoneal dissemination of gastric cancer--a case report

The most common treatment for patients of peritoneal dissemination of gastric cancer is a systemic chemotherapy, but the prognosis of these patients is very poor. For these diseases, some have reported the usefulness of intraperitoneal chemotherapy with cisplatin (CDDP), because of the direct cytotoxicity. Here, we report an effective treatment by chemotherapy with S-1 plus CDDP, intraperitoneal administration for the patients of peritoneal dissemination of gastric cancer. The patient was a 41-year-old male with upper abdominal pain. Upper gastrointestinal endoscopy showed a large type 3 gastric cancer from the cardia to antrum. Intraoperative peritoneal lavage cytology and dissemination was positive, thus we performed the total gastrectomy and implanted the intraperitoneal (IP) port in the Douglas's pouch. S-1 was given orally twice daily for the first 3 weeks of a 5-week cycle. CDDP was given as an intraperitoneal infusion on day 8 of each cycle. After 10 courses, he was treated with S-1 alone because he had an allergic reaction of CDDP. In 35 courses, he had survived for 5 years as disease free. Intraperitoneal chemotherapy may be a promising treatment for the patients who have peritoneal dissemination from gastric cancer.     

A case of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel

A 70-year-old man with gastric cancer of Borrmann type 3, liver metastases and peritoneal dissemination was treated by combination therapy of S-1 and docetaxel (DOC). He received DOC intravenously at 40 mg/m(2) on day 1 and S-1 orally at 100 mg/body on day 1 to 14, repeated every 28 days. After 2 courses of treatment, a CT scan revealed improvement of the gastric wall thickness, the eminent decrease of the peritoneal fluid and the reduction of the liver metastasis. After 3 courses of treatment, the primary lesion was remarkably improved on endoscopic examination, and the tumor marker normalized after 4 courses of treatment. Toxicities included leukocytopenia (WHO grade 3), neutropenia ( grade 3), anorexia (grade 2), and nausea (grade 2). Outpatient chemotherapy was possible by reduction of dose (S-1 100--> 80 mg/body, DOC 40--> 32 mg/m2). The response was maintained on CT and endoscopic examination after 21 courses of treatment. A case of an advanced gastric cancer patient successfully treated by combination therapy of S-1 and DOC was reported.     

Long-term survival case of advanced gastric cancer with paraaortic lymph node metastasis and peritoneal metastasis from S-1/CDDP combination therapy after reductive operation

A 72-year-old female patient with type 5 gastric cancer in the upper gastric region underwent surgery. Due to paraaortic lymph node metastasis (#16a1, #16a2) and peritoneal metastasis, total gastrectomy and D0 lymph node dissection were performed. Surgical and pathological findings were poorly differentiated adenocarcinoma, INFbeta, pT3(SE), PM (-), DM (-), ly0, v2, sN3 (#7, #9, #16a1-a2), M0, stage IV. The patient was administered S-1 for 2 weeks at 80 mg/day, received 24-hour continuous intravenous infusion of 80 mg/day on day 8, and then discontinued chemotherapy for 2 weeks, which was regarded as one course. After one course, CT scan showed that the paraaortic lymph node metastasis had almost entirely disappeared. However, due to grade 3 neutropenia, and grade 2 nausea and anorexia in the first course, the treatment was changed to oral administration of UFT (400 mg/day) , which was discontinued one month later due to anorexia. The patient has been in good health without a recurrence for 4 years after surgery. This case suggests that reduction surgery combined with a S-1 regimen is an effective treatment for long-term survival.     

The assessment of chemoradiation therapy with CDDP/S-1 for advanced gastric cancer that was actively bleeding

In the management of inoperable patients with advanced gastric cancer, it is important to control a tumor bleeding actively and to make sure that the patient can take meals through the stenotic cardia for the purpose of keeping the patients' quality of life well. We treated five gastric cancer patients with chemoradiation therapy consisting of CDDP (6 mg/m2) and S-1 (100 mg/body). In the treatment results, we have never seen an active tumor bleeding and anemic state, which required a blood transfusion after the treatment. In all of the 5 cases, a total quantity of taking meals increased due to a cardia stenosis improvement by tumor. We thought this treatment was useful for patients with cardia stenosis and actively bleeding in advanced gastric cancer.     

A case of advanced gastric cancer with lung metastasis effectively treated by combination chemotherapy using S-1 and CDDP

We report a case with gastric cancer and lung metastasis,who responded remarkably to combination chemotherapy using S-1 and weekly CDDP. A 59-year-old man was hospitalized for aphagia. Based on upper GI endoscopy and CT,type 3 gastric cancer associated with lung metastases was diagnosed. Cardiac gastrectomy, D 1 dissection, intermittented small intestine were performed. At 18 days postoperatively,the patient was administered 3 courses of S-1 (100 mg/body, on day 1-21) and CDDP (30 mg/body, on day 8, 15, 22) every 5 weeks. The treatment resulted in the metastatic tumors in the lung disappearing after 1 course. No severe adverse effects were observed. This combination chemotherapy proved useful for treating lung metastasis from gastric cancer in this patient.     

Chemotherapy in advanced gastric cancer--to ensure timely and appropriate switch to subsequent treatment options

Since irinotecan, S-1, docetaxel, and paclitaxel were approved, therapeutic options for chemotherapy in the treatment of gastric cancer have increased. It is suggested that the efficient use of the primary drugs prolongs life in the treatment of progressive colorectal cancer. Also, physicians have discussed ways to take full advantage of the drugs in the treatment of gastric cancer. In first-line treatment in other countries, combination therapy usually includes the administration of two drugs, while in Japan, where therapies based on S-1 have been developed, the most appropriate strategy must be determined after reporting the results of phase III trials in 2007. In the clinic, treatment must be selected on the basis of solid evidence in consideration of the organ dysfunction associated with progressive gastric cancer. The timing of any changes in the treatment should be considered because the cancer easily metastasizes to the peritoneum. Throughout the world, various regimens have been developed that replace cisplatin with oxaliplatin or mainly use oral fluoropyrimidine. Molecular target drugs, now being evaluated in phase II trials, will also be used in the treatment of gastric cancer in the near future. Novel therapies will be developed in Asia and Japan where the incidence of gastric cancer is high.