Three advanced gastric cancer cases with liver metastases successfully treated by TS-1/CDDP combination therapy

Three cases with unresectable advanced gastric cancer with liver metastases were successfully treated by the combination therapy of TS-1 and cisplatin( CDDP). TS-1 (1.25 m2>: 80 mg/day, 1.25 m2-1.50 m2: 100 mg/day, > or =1.50 m2: 120 mg/day) was administered orally for 14 consecutive days followed by 14 days rest,and a 24-h infusion of CDDP (70 mg/m2) was administered on day 8 of each course. Treatment was repeated every 4 weeks unless disease progression was observed. Partial response was obtained in all of the following three advanced gastric cancer cases with liver metastases. Case 1: 67-year-old male with Borrmann type I gastric cancer with multiple liver metastases. Case 2: 55-year-old female with multiple liver and lymph node metastases whose primary gastric lesion was surgically resected. Case 3: 53-year-old-male with Borrmann type III gastric cancer with liver and lymph node metastases. TS-1/CDDP therapy can be highly recommended for the treatment of advanced gastric cancer with liver metastases.     

A case of advanced gastric cancer with multiple liver metastases successfully treated with TS-1 and CDDP

A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with TS-1 and CDDP: Akihiro Tsukahara, Kazuhiro Kaneko and Syuji Tanaka (Dept. of Surgery, Niigata Prefectural Koide Hospital) Summary A 70-year-old advanced gastric cancer patient with liver and lymph node metastases was treated by chemotherapy with TS-1 and CDDP. One course consisted of administration of TS-1 100 mg/body for 21 days followed by 14 days rest and infusion of CDDP 80 mg/body on day 8. At the end of 2 courses, the primary tumor showed a hypertrophic wall, but a partial response of the liver metastases (reduction ratio was 78.3%) and a complete response of the LN metastasis were achieved. PR and CR were maintained after 4 courses. There were no remarkable side effects for 4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced gastric cancer with liver and lymph node metastases.     

Complete response in a case of advanced scirrhous type 3 gastric cancer of with bulky N2 para-aorta lymph node metastases treated by combined chemotherapy of TS-1 and CDDP

A 54-year-old patient with scirrhous type 3 gastric cancer having bulky N2 and para-aorta lymph node metastases was treated by combined chemotherapy of TS-1 and CDDP. Before treatment, CEA was 28.4 mg/ml. TS-1 (120 mg/day) administered for 14 days followed by 14 days rest was one course. CDDP (80 mg/m2) was administered by 24 hour continuous intravenous infusion at day 8 after the start of TS-1. After 2 courses of treatment, the level of CEA decreased to 1.4 mg/ml and the primary legion with lymph node metastases had decreased significantly. After 5 courses, endoscopic examination revealed complete disappearance of the primary tumor with no cancer cells detected by endoscopic biopsy. A CT scan also showed complete disappearance of all lymph node metastases. No severe adverse effects (NCI-CTC grade 3 of 4) were observed with this therapy. TS-1/CDDP chemotherapy is considered very effective for scirrhous gastric cancer with far advanced lymph node metastases.     

Two cases of advanced gastric cancer, successfully treated with TS-1/CDDP combination chemotherapy--case report

We reported 2 cases with advanced gastric cancer, successfully treated with TS-1 and CDDP. Case 1 had Type 3 gastric cancer with left supra-clavicular (Virchow) and para-aortic lymph node metastases. Those distant node metastases completely disappeared after two courses of neoadjuvant chemotherapy (NAC) consisting of TS-1/ CDDP, and radical surgery for cure was conducted. The second case had Type 3 carcinoma with peritoneal dissemination. The primary lesion significantly decreased after four courses of the combination chemotherapy. The patient has been alive for 1 year and a half after 14 courses of TS-1/CDDP with stable disease. Significance of TS-1/CDDP in far advanced gastric cancer was discussed.     

A case of advanced gastric cancer with invasion of pancreas effectively treated by combined chemotherapy of TS-1 and paclitaxel (TXL)

The patient was a 55-year-old woman who had unresectable advanced gastric cancer with celiac lymph node metastases and invasion of pancreas. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of TS-1 and low-dose CDDP, for a total of 3 courses of TS-1 (100 mg/day, 12 weeks) and 2 courses of low-dose CDDP (10 mg/day, 100 mg). The only side effect of this chemotherapy was light anorexia, and the patient maintained a good QOL. After chemotherapy, the tumor had decreased partially in size, but there was little change in the abdominal lymph node metastases. She was considered to have little response and underwent palliative distal gastrectomy, because of the incomplete dissection of abdominal lymph node metastases. After the operation, she was treated with 2 courses of TS-1 100 mg/day (3 weeks administration and 2 weeks rest) and CDDP 70 mg or 50 mg/body (day 8). She had grade 3 anorexia. After discharge, she was treated by combined therapy of TS-1 100 mg/day (2 weeks administration and 2 weeks rest) and TXL 60 mg/body (day 1, 8, 15). After 2 courses of TS-1/TXL therapy, the abdominal lymph node metastases had decreased in size and the tumor markers were reduced remarkably: CEA 146.1-->26.9 ng/ml, and CA19-9,351.5-->210.6 U/ml. The patient received 5 courses of TS-1/TXL therapy, and she had no trouble with side effects. She maintained a good QOL. TS-1/TXL therapy was associated with few adverse events in hospital visits, and thought to be an effective adjuvant chemotherapy against advanced gastric cancer.     

Complete response in a case of advanced gastric cancer with liver and intra-abdominal lymph node metastases treated by combined chemotherapy of TS-1 and CDDP]

A 67-year-old male patient with gastric cancer of Borrmann type 2 and liver and intra-abdominal lymph node metastases was treated by combined chemotherapy of TS-1 and CDDP TS-1 (100 mg/day) was administered for 14 days followed by 14 days rest as one course. CDDP (70 mg/m2) was administered in 24-hour continuous intravenous infusion at 8 days after the start of TS-1. After 3 courses of treatment, X-ray and endoscopic examinations revealed complete disappearance of the primary tumor and no cancer cells were detected by endoscopic biopsy. A CT-scan also showed complete disappearance of metastatic sites. This combined chemotherapy was finished after 5 courses, and no high grade toxicities (WHO grade 3 or 4), specifically nausea, diarrhea, or leucocytopenia, were seen. This TS-1/CDDP chemotherapy seemed to be effective for advanced gastric cancer in view of toxicities, antitumor effect and QOL of the patient.     

A case of advanced gastric cancer successfully treated by TS-1 and CDDP after jejunostomy

A 65-year-old female with unresectable advanced gastric cancer accompanied by multiple lung metastases underwent jejunostomy and was treated with TS-1 and CDDP. One course consisted of TS-1 (80 mg/day) via an intestinal fistula tube from days 1 to 14 followed by 14 days rest and CDDP (80 mg/day) was administered by 24-hour continuous intravenous infusion on day 8. After 3 courses, the primary tumor and lymph node metastases decreased in size (PR), and CT scan showed the multiple lung metastases had disappeared. Total gastrectomy (D 2) and splenectomy were performed after chemotherapy. The final diagnosis was Stage IIIA and the pathological response to chemotherapy was Grade 2. The patient has survived for over 14 months after surgery and has presented no signs of recurrence.     

Two cases of gastric cancer with multiple liver metastases responding to TS-1 with hepatic arterial infusion of CDDP following low-dose 5-FU and CDDP chemotherapy

Case 1: A 77-year-old man was revealed to have type 3 gastric cancer with synchronous liver metastases. He underwent total gastrectomy with lymphatic dissection of D1+a and tubing of the hepatic artery. After surgery, two courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. The patient was discharged, and TS-1 (60 mg/day) was administered from day 1 to 14 followed by 7 days rest as one course. CDDP (10 mg/ body) was infused in the hepatic artery bolus on day 8 and 15 as outpatient treatment. After 8 months, the CEA was decreased from 3,098 ng/dl to 5.4 ng/dl, hepatic metastases were decreased by 85% assessed as a partial response. Case 2: A 71-year-old man was diagnosed with multiple liver metastases 10 months after distal gastrectomy for early gastric cancer. After tubing of the hepatic artery, three courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. TS-1 with hepatic arterial infusion of CDDP was administered using the same regimen as an outpatient. After 4 months, hepatic metastases decreased by 73%. These cases suggest that TS-1 with hepatic arterial infusion of CDDP in an outpatient may be an effective treatment with low toxicities and no damage to QOL in gastric cancer patients with multiple liver metastases.     

A case of advanced gastric cancer which became operable after chemotherapy with combination of TS-1/CDDP and in which complete disappearance of liver metastasis was histopathologically confirmed

We encountered a patient in whom TS-1/cisplatin (CDDP) combination chemotherapy was effective. The cancer became operable, and complete disappearance of liver metastasis was histopathologically confirmed. The patient was a 65-year-old man who presented with complaints of epigastric discomfort and anorexia. Based on upper GI endoscopy and abdominal CT, type 1 gastric cancer associated with liver and abdominal lymph node metastases was diagnosed. The cancer was judged to be inoperable, and chemotherapy with a combination of TS-1 and CDDP was initiated. One course of treatment consisted of administration of 120 mg/day of TS-1 for 21 days followed by 14 days of withdrawal, and administration of 100 mg/body/day of CDDP on day 8 (80 mg/body/day in the second course). After two courses of treatment, the primary lesion and the liver and lymph node metastatic lesions decreased in size (reduction ratios were 42.3%, 90.5% and 85.2%, respectively). The tumor marker values became normal. Subsequently, the cancer was judged to have become operable. After consultation with the patient, total gastrectomy, splenectomy, partial hepatectomy, and D3 dissection were performed, and curability B was achieved. The only adverse event of Grade 2 or more severity observed during drug administration was anorexia. Liver metastasis was judged from pathological findings to have disappeared. The postoperative course was uneventful and the patient was discharged from the hospital. To date, there have been no signs of recurrence. TS-1/CDDP therapy is believed to provide effective treatment against liver metastasis and lymph node metastasis of gastric cancer.     

A case of gastric adenosquamous carcinoma with abdominal paraaortic lymph node metastases successfully treated by TS-1 plus CDDP neoadjuvant chemotherapy

A 62-year-old woman was admitted for anemia. An endoscopic examination revealed type 2 cancer from the upper body of the stomach to the antrum, and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative diagnosis was cStage IV gastric cancer (cT 3, cN 3, cH 0, cP 0, cM 0). Since a curative operation was deemed impossible, we conducted neoadjuvant chemotherapy using TS-1 plus cisplatin (CDDP) for downstaging. TS-1( 100 mg/day) was orally administered for 3 weeks,and CDDP (60 mg/m2) was given intravenously on day 8. Appetite loss of grade 3 and erythropenia of grade 1 were observed. After two courses of chemotherapy the primary lesion and the paraaortic lymph nodes were significantly reduced in size. She was judged as clinical PR, followed by distal gastrectomy and lymph node dissection, resulting in curability A. Histopathologically, the tumor was diagnosed as adenosquamous carcinoma of the stomach with lymph node metastasis at only No.3. This case suggests that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric adenosquamous carcinoma with massive lymph node metastases.     

Two cases of advanced and recurrent gastric cancer responding markedly to TS-1/CDDP therapy

Case 1: A 77-year-old woman with advanced gastric cancer and peritoneal dissemination was treated with TS-1/CDDP therapy. TS-1 (100 mg/day) was orally administered for 21 days and CDDP (70 mg/body) was administered intravenously on day 8. After 2 courses reduction in size of the primary carcinoma was observed (PR). The duration of the PR and the survival time were over 1 year and 6 months. Case 2: A 77-year-old woman with recurrent abdominal and liver metastasis from advanced gastric cancer was treated with TS-1/CDDP therapy. TS-1 (100 mg/day) was orally administered for 21 days and CDDP (80 mg/body) was administered intravenously on day 8. The reduction was judged to be CR for the liver metastasis and PR for the abdominal tumor (total judgment: PR). The duration of the PR and the survival time were over 1 year and 5 months. It is suggested that TS-1/CDDP chemotherapy is useful for advanced and recurrent gastric cancer.     

A case of gastric cancer with abdominal para-aortic lymph node metastases responding to TS-1 + CDDP neoadjuvant chemotherapy

The patient was a 54-year-old woman with extremely advanced gastric cancer of type 3. A CT scan of the abdomen showed enlargement of many huge abdominal para-aortic lymph nodes. Combined chemotherapy of TS-1 and CDDP was planned in order to reduce the tumor. TS-1 (100 mg/body/day) was administered for 21 days followed by 14 days rest as one course. CDDP (96 mg/body) was administered 8 days after the start of TS-1. After 2 courses of treatment, a CT scan showed complete disappearance of lymph node metastasis, and no high grade toxicities. Therefore, one month after the completion of the chemotherapy, total gastrectomy and D2 lymph node dissection were performed. The histological effect was judged to be grade 1a-1b. There were no viable cancer cells in any lymph nodes. One year after surgery, the patient is still alive without recurrence. Neoadjuvant chemotherapy with TS-1 and CDDP is so effective that can it be adapted for advanced gastric cancer with para-aortic lymph node enlargement for downstaging.     

A case of metastatic gastric cancer treated with CDDP plus TS-1 and surgical resection

Advanced gastric cancer (AGC) with liver metastasis has a poor prognosis. We encountered a case of AGC with multiple liver metastasis treated with chemotherapy and surgery. Case: A 54-year-old male. He was admitted to our hospital with epigastric pain. Gastrointestinal fiberscope examination revealed gastric cancer. A CT scan showed regional and para-aortic lymph node (LN) swelling and multiple hepatic metastasis in the left hepatic lobe. The serum CEA level was 100.6 ng/dl. He was administered 4 courses of CDDP (100 mg (day 8 i.v.)) plus TS-1 (120 mg/day day 1-21 p.o.). After the chemotherapy, CT showed a reduction of liver metastasis and disappearance of the LN swelling. The serum CEA levels were normalized. Distal gastrectomy, partial hepatectomy, and microwave coagulation therapy were performed. After operation, he was administered 4 courses of CDDP/TS-1 additionally. Surgery may be one of therapeutic option for AGC with liver metastasis that has responded to chemotherapy, as in the present case.     

Three successful case reports of advanced gastric cancer with chemotherapy

We report three successful cases with continuous systemic chemotherapy for advanced gastric cancer. Case 1: A 67-year-old male with gastric cancer. Abdominal CT showed the invasion in the pancreas and as a result, continuous systemic infusion of low-dose cisplatin (CDDP 20 mg/day) and 5-fluorouracil (5-FU 1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 25 days. Three months after the chemotherapy, the main tumor was remarkably reduced (downstaging was obtained), and consequently, total gastrectomy was performed. Case 2: A 78-year-old male with gastric cancer and hepatic multiple metastases. Abdominal CT scan before operation did not reveal the hepatic metastasis. In the operation for distal gastrectomy, we found multiple metastases on the surface of the liver. Continuous systemic infusion of low-dose CDDP (20 mg/day) and 5-FU (1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 2 days. One month after the chemotherapy, Liver metastases had almost disappeared. Case 3: A 73-year-old male had received a distal gastrectomy based on the diagnosis of gastric cancer. The tumor marker, CA19-9, immediately decreased after the operation, but had increased again. He was treated with a combination chemotherapy of TS-1 and CDDP. The treatment consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. CDDP of 10 mg/day was infused intravenously (day 1-5). Four weeks after the infusion, CA19-9 had returned to almost normal. We conclude that the combination chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for advanced and metastatic gastric cancer.     

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 resected case of stage IV gastric cancer successfully treated with TS-1/CDDP as neoadjuvant chemotherapy

A resected case of gastric cancer is described. The patient was a 60-year-old woman who presented a type 3 gastric tumor complicated by invasion of the head of the pancreas and liver. Radical resection was not indicated, and we administered the following combination chemotherapy with TS-1 and CDDP. 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks as 1 course and 9 5 mg (60 mg/m(2)) of CDDP was administered intravenously on day 8. After two courses, total gastrectomy and D2 lymph node dissection were performed. Radical surgery for cure was conducted. Microscopically, the histological effect was judged to be grade 1a. One year after the operation, the patient is still alive without recurrence and metastasis. TS-1/CDDP therapy is useful for advanced gastric cancer.     

A case of gastric cancer with abdominal paraaortic lymph node metastases responding to TS-1 plus CDDP neoadjuvant chemotherapy

A 62-year-old woman was admitted because of epigastralgia and tarry stool. An endoscopic examination revealed type 3 cancer in the lower body of the stomach, and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative diagnosis was cStage IV gastric cancer (cT3, cN3, cH0, cP0, cM0). Since a curative operation was deemed impossible, we started neoadjuvant chemotherapy using TS1 plus cisplatin (CDDP) for downstaging. TS-1 (100 mg/day) was orally administered for 3 weeks, and CDDP (90 mg/body) was administered intravenously on day 8. Appetite loss of grade 3 and leucopenia of grade 1 were observed. After two courses of chemotherapy, the primary lesion was reduced in size, and the paraaortic lymph nodes disappeared on abdominal CT scan. The serum tumor marker became normal. Subsequently, she underwent curative total gastrectomy with splenectomy and lymph node dissection. Histological examination of the primary lesion revealed marked fibrosis and a small amount of residual cancer cells. The histological changes by neoadjuvant chemotherapy were judged to be grade 2 for the main tumor. It is suggested that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric cancer with massive lymph node metastases.     

A case of advanced gallbladder cancer with biliary tract stenosis which responded to TS-1 chemotherapy

TS-1 is reported to be beneficial for advanced gastric cancer, but there is no report on its use for advanced gallbladder cancer. The present patient was a 64-year-old woman with advanced gallbladder cancer with severe biliary tract stenosis. The primary tumor was located in the neck of the gallbladder and peripancreatic lymph node metastasis was detected. TS-1 100 mg/day was administered orally for 21 days and CDDP 30 mg/day on days 1, 8 by drip infusion. Grade 4 neutropenia was observed in the first cycle, and TS-1 alone was used for further treatment. After 2 courses, primary tumor showed PR and lymph node metastasis had disappeared. Biliary stenosis was remarkably improved. We conclude that TS-1 might be beneficial in the treatment of advanced gallbladder cancer.     

A case report of the 8 year survivor--unresectable liver metastases from advanced gastric cancer (Stage IV) were completely responsive, after 4 years from a total sequential gastrectomy, combining docetaxel treatment to regress the recurrence

This case was a 69-year-old male who had advanced gastric cancer with unresectable multiple liver metastases (Stage IV). He received a combination therapy consisting of a continuous venous infusion (cisplatin: CDDP 10 mg/body, 5-FU 500 mg/body, day 1-28). As a result, metastatic tumors in the liver completely disappeared and a total gastrectomy was sequentially performed. Four years after the surgery, neck lymph node (LN) metastases and the right adrenal metastasis appeared, and chemotherapy (TS-1, and sequentially TS-1+CDDP) was performed. But, the chemotherapy to eradicate the metastases was hardly enough to be effective. Next, docetaxel (DOC 60 mg/m2 q3w) was started. After 9 courses, they were effective and marked regressions (70%). A total of 15 courses of docetaxel administration were possible until tumor progression recurred. This regimen was not severe in toxicity for the duration except for grade 3 poor appetite. Docetaxel will be a key drug for the gastric cancer. In case of responding well to the chemotherapy, we can hope for an extended long-term survival with a continuation of this regimen.     

A resected case of advanced gastric cancer with multiple liver metastasis responding to preoperative TS-1/CDDP chemotherapy

Case: A 75-year-old man was admitted to our hospital with hematoemesis. Gastrofiber-scopy revealed that type 3 gastric cancer was widespread in the lesser curvature. Multiple liver metastases 5 cm in diameter were shown on CT. We thought that the case was unresectable, and TS-1/CDDP chemotherapy was performed. TS-1 (80 mg/body/day) was orally administered and CDDP at 20 mg/body/day by intravenous drip infusion a week for 3 weeks followed by a drug-free 2 week period as the first course. After the third course, the primary lesion and the liver metastasis showed a partial response in terms of size. No serious drug adverse reaction was observed. Since there was no longer any reduction of the tumor, gastrectomy and coagulation therapy for liver metastasis were performed, and he has been alive for 15 months without recurrence. Combined use of TS-1 and CDDP is effective as neoadjuvant chemotherapy for advanced gastric cancer.