A case of advanced gastric cancer with obstructive jaundice due to multiple liver metastasis successfully treated with the following combination therapy of CPT-11 and cisplatin after combination therapy of paclitaxel and TS-1

A 60-year-old man, who had been admitted to another hospital with complaints of constipation, abdominal fullness and appetite loss, was referred to our hospital for further examination and therapy. The patient was diagnosed as advanced gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice. He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was orally administered for 2 weeks followed by one drug-free week), and showed a remarkable response. However, because of ascites, elevated serum CEA level and resistance in the liver metastasis and gastric region, we attempted two courses of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT-11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1 followed by two drug-free weeks) which showed a remarkable response. Two courses of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT-11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed by two drug-free weeks) on an outpatient basis. However, the patient showed resistance to the latter combination therapy, increased ascites due to suspicious peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the liver. He died on May 23, 2006, about ten months after initial diagnosis. We reported a case of successful treatment of combination chemotherapy for advanced gastric cancer with obstructive jaundice due to progressive multiple metastatic tumors in the liver and obtained comparative long-term survival maintaining high quality of life.     

A case of TS-1 resistant recurrent gastric cancer responding to TS-1 +CPT-11 combination therapy

A 71-year-old man underwent distal partial gastrectomy for gastric cancer. Four years after surgery, the tumor marker was elevated. Examinations by computed tomography (CT) revealed para-aortic lymphnode swelling and hydronephrosis. The patient treated oral administration of TS-1 (120 mg/day). After 3 courses of treatment of TS-1, progressive disease was observed. TS-1+CPT-11 (TS-1 120 mg/day day 1-14, CPT-11 100 mg/day day 1, 15) combination therapy was then chosen as second-line chemotherapy. After 5 courses of combination therapy, the tumor marker was decreased and para-aortic lymphnodes could not be detected by CT. Only grade 2 leukopenia was observed as an adverse event during the therapy. TS-1+CPT-11 combination therapy could be useful as the second-line chemotherapy for cases of TS-1 resistant recurrent gastric cancer.     

A case of gastric cancer with multiple liver metastases and spleen metastasis that responded to low-dose CDDP/TS-1 combination therapy

Since the introduction of TS-1 for clinical treatment of the progression or recurrence of stomach cancer, the effectiveness of combination therapy incorporating other agents with CDDP has been reported. Low-dose CDDP/TS-1 combination treatment was carried out in a case of Stage IV progressive stomach cancer showing multiple liver metastases and spleen metastasis. Regression of the primary carcinoma and reduction in size of liver metastases and spleen metastasis were observed. Grade 2 leukocyte decrease and grade 1 stomatitis were noted as adverse reactions to the treatment. Low-dose CDDP/TS-1 combination therapy was useful in this case of advanced gastric cancer.     

A case of gastric cancer presenting with obstructive jaundice and responding to biweekly CPT-11 and CDDP combination administration

A 74-year-old man was suffering from Borrmann type 2 advanced gastric cancer with abdominal lymph node metastases and multiple lung metastases. He started to undergo outpatient treatment with oral administration of TS-1. But pyloric stenosis was found after 6 courses of TS-1 chemotherapy, so he underwent palliative distal gastrectomy. TS-1 chemotherapy was continued afterwards, however obstructive jaundice was found. So combination chemotherapy of CPT-11 60 mg/m(2)and CDDP 30 mg/m(2)biweekly was selected as a second-line therapy after PTCD. As no side effects were found, he could be treated on an outpatient basis by CPT-11 60 mg/body and CDDP 30 mg/body biweekly. Four months has passed since the palliative operation, and the PTCD tube was successfully removed. The abdominal lymph nodes had decreased in size and the patient has maintained good QOL. Thus, combination CPT-11 and CDDP therapy could well be a new candidate for a second-line chemotherapy in outpatients.     

A case of advanced gastric cancer with pyloric stenosis and obstructive jaundice responding to s-1/paclitaxel combination therapy after endoscopic balloon dilatation and endoscopic biliary drainage

A 65-year-old female who complained of appetite loss and upper abdominal pain was diagnosed as unresectable advanced gastric cancer with pyloric stenosis and obstructive jaundice by peritoneal and lymph node metastases. After endoscopic balloon dilatation and endoscopic biliary drainage, S-1(80 mg/m(2)/day, days 1-14 with 1 week rest)/pacli- taxel(PTX)(50 mg/m(2)/day, day 1, day 8)combination therapy was done. After one course of the chemotherapy, subjective symptoms were relieved and oral intake was increased. Computed tomography showed that the volume of gastric wall, the size of paraaortic lymph node, and the amount of pleural effusion and ascites were decreased. Grade 1 alopecia, vasculitis and grade 2 neutropenia were observed as adverse reactions to the treatment. S-1/PTX combination therapy after endoscopic intervention was effective in this case of advanced gastric cancer with pyloric stenosis and obstructive jaundice.     

A case of gastric cancer with umbilical metastasis that responded to TS-1 with low-dose cis-platinum

An umbilical metastasis of gastric cancer is known as Sister Mary Joseph's nodule. It ordinarily indicates a poor prognosis because umbilical metastasis often develops with peritoneal dissemination. Herein, we report a case of umbilical metastasis of gastric cancer that showed good response to chemotherapy, including the oral anticancer agent TS-1. The patient was a 55-year-old man in which gastric cancer was found by upper gastrointestinal series. Physical examination revealed an umbilical nodule that had an irregular surface and a hard consistency. Ultrasonography showed a 15 x 10 mm hypoechoic mass under the umbilicus. Core needle biopsy of the umbilical mass revealed adenocarcinoma. Peritoneal dissemination was proved by diagnostic laparoscopy. Oral anticancer agent TS-1 was administered with low-dose cis-platinum. The gastric lesion and umbilical nodule showed marked response to the chemotherapy and the response continued for 20 months. The patient died of disease progression 31 months after the initiation of the treatment.     

A case of rectal cancer with multiple liver metastases that responded dramatically to pharmacokinetic modulating chemotherapy/CPT-11 therapy

A 67-year-old male patient suffering from rectal cancer complicated by multiple hepatic metastases underwent low anterior resection, cholecystectomy and hepatic arterial cannulation. He was treated postoperatively with arterial infusion pharmacokinetic modulating chemotherapy (PMC) and venous infusion CPT-11 (modified PMC). After three courses of modified PMC, a complete response (CR) of the hepatic metastatic lesions was noted. PMC/CPT-11 therapy was managed at our outpatient clinic, and seems to be a useful treatment option.     

A case of gastric carcinoma with metachronous liver metastases that responded to percutaneous ethanol injection therapy (PEIT) and TS-1

A 57-year-old male underwent a total gastrectomy with D1 lymph node dissection for gastric carcinoma. The main tumor was located in area UM, measuring 15 x 6 cm and was classified as type 5. Histopathologically, the cancer cells invaded the subserosal layer with a moderately differentiated tubular pattern. Lymph node metastases (No. 1, 3, 7 and 9) were detected. Lymphatic involvement was revealed (ly 2). Three years after the first surgery, a liver metastasis (area S4) with a diameter of 30 mm was detected by abdominal ultrasonography. Percutaneous ethanol injection therapies (PEIT) were performed twice for the lesion. After PEIT, a TS-1 intake program (80 mg/day, for 4 weeks) was started for the metastatic lesion. Both treatments were effective. The patient has survived without recurrence for over 5 years after the total gastrectomy.     

A case of advanced gastric cancer responding to neoadjuvant TS-1/CDDP therapy

A 62-year-old advanced gastric cancer patient with bulky N2 lymph node metastases was treated by neoadjuvant chemotherapy with TS-1 and CDDP. TS-1 (100 mg/body/day) was orally administered for 3 weeks followed by a drug-free 2-week period as 1 course, and 75 mg/body/day of CDDP was administered by intravenous drip on day 8. After the first course, the primary lesion and the regional lymph node metastases showed partial response in terms of size. No serious drug adverse reaction was observed. During the second course, urgent total gastrectomy with distal pancreatectomy and splenectomy was performed for massive bleeding from a deep gastric peptic ulcer. The histopathological findings showed complete response of the carcinoma as primary lesion except for two sites of minimal lymphatic permeation and one lymph node (No. 8a) metastasis. The combined use of TS-1 and CDDP is useful as neoadjuvant chemotherapy for advanced gastric cancer.     

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 non-curatively resected colon cancer with liver and lymph node metastases treated by TS-1/CPT-11 combination therapy

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.     

A case of advanced gastric cancer with lymphangitis carcinomatosa after operation of Krukenberg tumor treated by TS-1 plus CPT-11 as third-line chemotherapy

Chemotherapies for recurrent gastric cancer have not yet been established. Here we report a case of type 4 gastric cancer associated with lymphangitis carcinomatosis which became refractory to the previous chemotherapies. The case was a 40-year-old woman. She had been diagnosed with gastric cancer after a Krukenberg tumor operation. Chemotherapies (TS-1 plus CDDP as first-line, and TS-1 plus taxanes as second-line) were performed, and a partial response was achieved. Disease activity has been well controlled until this time. Since recurrence of left pleural effusion and lymphangitis carcinomatosis was recognized, we changed the chemotherapy TS-1 plus CPT-11. Pleural effusion decreased and lymphangitis carcinomatosis improved. The serum CA 19-9 level rose transiently after CPT-11 administration, and tended to fall at the second week of chemotherapy. However, the patient died 2 years 4 months after the onset. TS-1 plus CPT-11 combination chemotherapy would be effective for lymphangitis carcinomatosis and also useful as third-line chemotherapy for recurrent gastric cancer.     

A case of advanced gastric cancer with peritoneal metastasis that responded to paclitaxel plus 5-FU therapy

We report a case in which paclitaxel (PTX) plus 5-FU therapy was remarkably effective for advanced gastric cancer with peritoneal metastasis. The patient was a 41-year-old woman who had type 4 gastric cancer with peritoneal metastasis. PTX plus 5-FU therapy was performed. The regimen included 600 mg/body/day of 5-FU by continuous iv administration from day 1 to 5 and consequent administration of PTX (90 mg/body) on days 8, 15 and 22 for 28 days repetitively. After 4 courses were completed, abdominal CT revealed that ascites had disappeared and the stomach wall had become thinner. Thus,we considered the patient had a partial response, and performed total gastrectomy. After the operation, PTX plus 5-FU therapy was used for 8 courses with the same regimen. No serious adverse event was observed,and the patient maintained good QOL throughout the treatment. No sign of progressive disease was seen for 12 months after the operation. However, 18 months after beginning the treatment, peritoneal metastasis became worse, and she died 19 months after treatment had begun. Considering the effectiveness and mild toxicity, PTX plus 5-FU therapy is thought to be useful for advanced gastric cancer.     

Complete response of recurrent gastric cancer to chemotherapy with TS-1 and CPT-11--a case report

A 58-year-old man with gastric cancer who had undergone distal gastrectomy on February 8, 2001 was revealed to have anorexia, and was diagnosed with a local recurrence in anastomosis by upper GI examination in August 2003. In September 2003, he was given combination chemotherapy with TS-1 50 mg/m2 (days 1-14) and CPT-11 80 mg/m2 (days 1, 8) every 3 weeks. A complete response (CR) was confirmed by endoscopy in December 2003. At present, he has been receiving chemotherapy with only TS-1 50 mg/m2 as a maintenance therapy and continuing CR. However, a trial of combination therapy with TS-1 plus CPT-11 is ongoing, and this combination chemotherapy may well achieve a high response rate. Because the adverse events of this chemotherapy have been mild and tolerable in some of our cases, this regimen is considered very useful.     

A case of advanced gastric cancer with liver and lung metastases markedly responded to TS-1-based sequential chemotherapy

A 61-year-old man with multiple liver and lung metastases from advanced gastric cancer was admitted to our hospital. We selected the patient from the outpatient department and started a single administration of TS-1 as a first line chemotherapy. TS-1 was markedly effective and the CEA level decreased 4,528 ng/ml to 44 ng/ml only in three months. The clinical response was assessed to be partial response (PR) comparable to complete response (CR) according to the tumor regression effect. The effect had been continued for almost six months. Because the CEA level elevated again, we estimated that the tumor acquired a drug tolerance to TS-1. Therefore, we applied CDDP with TS-1 as a second line chemotherapy. Unfortunately, it was not effective. Then we combined paclitaxel (PTX) to TS-1. The CEA level was remarkably reduced again, but transiently. Thereafter, we continued a sequential administration of TS-1 plus other drugs (CPT-11, docetaxel and MMC). Over 2 years, the patient is alive with a good quality of life.     

A case of advanced gastric cancer with peritoneal dissemination responding remarkably to TS-1/CDDP combination chemotherapy

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.     

A resected case of advanced gastric cancer after treatment with low-dosage TS-1

We report a case of advanced gastric cancer that responded well to low-dosage TS-1. A 72-year-old woman was diagnosed as having unresectable advanced gastric cancer with ascites and hydronephrosis in the right kidney. She was treated with chemotherapy using a low-dosage of TS-1 (80 mg/body/day) administered perorally for 4 weeks followed by a drug-free 2 weeks, in six-week cycles. However, she developed weight loss, appetite loss, and stomatitis. We therefore reduced the dosage of TS-1 from 80 mg/body/day to 60 mg/body/day. The ascites and hydronephrosis gradually improved during the following 3 months, whereupon she could undergo total gastrectomy. The postoperative findings showed no ascites and no peritoneal dissemination. The postoperative pathological findings showed that the cancer cells were localized to within the mucosa, and there were no cancer cells in the greater and lesser omentum. Three weeks after the operation, TS-1 was resumed at 60 mg/body/day. However, 3 months later,ascites and metastasis to the abdominal skin developed, and she died 9 months after the operation.     

Locally advanced pancreatic cancer that enlarged after administration of gemcitabine and responded to oral TS-1--a case report

We administered oral TS-1 alone for locally advanced pancreatic cancer that did not respond to gemcitabine (GEM). A 56-year-old man was admitted to our hospital because of obstructive jaundice due to stage III pancreatic head cancer. We performed chemotherapy using GEM at a dose of 1,000 mg/m(2) after reduction of jaundice by PTCD and stenting. Once the tumor was reduced, enlargement was confirmed after 8 months, and cholangitis appeared due to stent obstruction. After PTCD and stenting (stent in stent) were performed again,we administered oral TS-1 alone at a dose of 100 mg/body. We achieved antitumor activity again using TS-1. It is suggested that TS-1 is a useful second-line agent for pancreatic cancer.     

A case of TS-1 resistant recurrent gastric cancer with lung metastasis responding to TS-1 and irinotecan combination therapy

We report a case of TS-1-resistant recurrent gastric cancer with lung metastasis responding to TS-1 and irinotecan (CPT-11) combination therapy. A 72-year-old man underwent total gastrectomy with pancreaticosplenectomy for advanced gastric cancer on October 18, 2001, and partial hepatectomy for postoperative liver metastasis on August 22, 2002. In March 2004, a chest computed tomography scan revealed metastatic lesions in the bilateral lungs, and he received a single administration of TS-1, resulting in partial response. After 13 courses, this therapy was discontinued due to progressive disease. Then,TS-1 and CPT-11 combination therapy was chosen as the second-line chemotherapy. After 4 courses, a partial response was obtained in lung metastasis, and thereafter has been maintained. He has been treated on an outpatient basis because of no grade 3 or severer adverse reactions. TS-1 and CPT-11 combination therapy could be a promising regimen as the second-line chemotherapy for gastric cancer resistant to TS-1.     

A case of gastric cancer with multiple liver metastasis responding to combination therapy of CPT-11 and CDDP

A 63-year-old man suffering from advanced gastric carcinoma after distal gastric resection had multiple liver metastases 5 months after the operation. He underwent 3 courses of combination chemotherapy of 5-FU 600 mg/day with CDDP 50 mg/day, etoposide 100 mg/day and Leucovorin 30 mg/day for 5 days (FLEP), but progressive disease (PD) was noted. One additional course of combination chemotherapy with CPT-11 140 mg/day and CDDP 40 mg/day biweekly was performed and a complete response (CR) was noted. After 4 months, recurrence of a liver metastasis on S8 was demonstrated and 2 courses of the same chemotherapeutic regimen were carried out. Over 5 months, recurrence of the liver metastasis showed no change (NC) and resection of S8 of the liver was performed. No recurrence was after 6 months, but the patient died 34 months after the first detection of the occurrence of multiple liver metastases. The combination chemotherapy of CPT-11 with CDDP was also administered to other patients at our outpatient clinic and seems to be useful therapy for improving outcome.