A case of distant metastasis from advanced gastric cancer treated with TS-1, which maintained NC (no change) for 9 months

A 57-year-old woman was admitted to our hospital for advanced gastric cancer located in the gastric antrum. Abdominal CT scan revealed multiple liver metastases and lymph node metastasis along the abdominal aorta which was diagnosed as stage IV gastric cancer. The patient received daily oral administration of 75 mg TS-1, a novel oral anticancer agent. Each treatment course consisted of a four-week administration followed by two drug-free weeks. No change (NC) was observed in the liver metastasis on the abdominal CT scan after TS-1 administration, but lymph node swelling along the abdominal aorta decreased (PR). Grade 2 depilation was observed as the only adverse effect. The patient had a performance status of 1 or 2, and kept a fair QOL. TS-1 is an excellent new anticancer agent and, we have high expectations for its use in combined therapy with other drugs.     

Successful treatment of gastric cancer accompanied by multiple liver metastases with TS-1 followed by curative gastrectomy affiliation

Despite the improvement in the operative results for patients with gastric cancer, the prognosis of those with liver metastasis remains dismal. Multimodal therapy has attracted considerable attention as a breakthrough in the strategy for treating cases of highly advanced gastric cancer. We report the case of a 62-year-old female with gastric cancer accompanied by multiple liver metastases successfully treated by TS-1, a novel oral fluoropyrimidine derivative. One treatment course consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. After 3 courses of treatment, an abdominal CT scan showed no evidence of liver metastases and gastroscopy revealed that the primary gastric lesion was reduced. Grade 1 toxicity (nausea and diarrhea) was seen but 6 days rest improved the condition. Distal gastrectomy was subsequently performed without any finding of residual tumor. TS-1 may have a promising role in neoadjuvant chemotherapy for 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.     

Two cases of stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy

CASE 1: A 72-year-old man with epigastralgia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed liver metastasis and para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 4 courses of this treatment, the liver metastasis and para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. There has been no recurrence for 16 months postoperatively. CASE 2: A 66-year-old man with anorexia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 9 courses of this treatment, para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. Eight months after the operation, lymph node metastases were confirmed by abdominal CT scan, and he was treated with chemotherapy as an outpatient as of 13 months after the operation. We experienced two cases of Stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy. It was suggested that adjuvant surgery to highly advanced gastric cancer could improve the prognosis of patients.     

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.     

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.     

Clinical efficacy of TS-1 combined with cisplatin for advanced cardiac gastric cancer with multiple liver metastases--two case reports

Case 1: A 62-year-old man was introduced to our hospital for Type 1 cardiac gastric cancer. On the abdominal CT, there was evidence of multiple liver metastases. The patient was treated with daily oral administration of TS-1 (120 mg/day) for 3 weeks followed by 2 weeks' rest and infusion of CDDP (60 mg/m2) on day 8 as 1 course. After completion of 1 course, partial response in the primary tumor, and complete responses in the liver and lymph node metastases had been assessed, although the primary tumor increased during the 2 months' rest after 4 courses. Case 2: A 67-year-old man was hospitalized for Type 3 cardiac gastric cancer with multiple liver and lymph node metastases. A combination of TS-1 (100 mg/day), and CDDP (60 mg/m2), and TS-1 (80-50 mg/ day) was used. After 2 courses of TS-1/CDDP and 4 courses of TS-1, the primary tumor decreased significantly in size, and complete responses in the liver and lymph node metastases had been assessed, although the primary tumor, liver and lymph node metastases increased after 6 courses of TS-1. The two cases under study suggest that the combination systemic chemotherapy of TS-1 and CDDP is an effective treatment for advanced gastric cancer with multiple liver metastases in terms of its antitumor effect and QOL of the patients.     

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.     

A case of type 4 gastric cancer,diagnosed after operation for Krukenberg's tumor,treated by TS-1 plus low-dose cisplatinum

Survival of patients with advanced gastric cancer with Krukenberg's tumor is poor. We report the case of a good response in a 37-year-old woman who had type 4 gastric cancer, diagnosed after the operation of Krukenberg's tumor, and then was treated with TS-1, a DPD inhibitory fluoropyrimidine, in combination with a low-dose cisplatinum (CDDP). Endoscopic gastric biopsy showed signet-ring cell adenocarcinoma and moderately differentiated tubular adenocarcinoma, and computed tomography (CT) showed the para-aortic lymph node metastasis before the chemotherapy. The patient was treated with two courses of TS-1 (100 mg/day, day 1-21) plus CDDP (10 mg/m2, day 1-5, 8-12, 15-19) with two-week interval. After the first course, gastric biopsy did not show any cancer cells and lymph node metastasis had disappeared. Serum CA19-9 decreased gradually week by week during the chemotherapy, even during the washout period after the first course, and was normalized after two courses. This case suggests that the combination of TS-1 and low-dose CDDP is effective against type 4 advanced gastric cancer.     

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.     

A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP combination therapy

A 53-year-old man had consulted another physician regarding his epigastralgia and anorexia. Since gastric cancer was detected, he was referred to our department. An upper gastrointestinal endoscopy revealed a type-2 gastric cancer at the upper portion of the lesser curvature of the stomach, and an abdominal CT scan showed marked swelling of periaortic lymph nodes. Since a radical resection appeared impossible, we used preoperative chemotherapy with a combination of TS-1 and CDDP. The patient was administered TS-1 for 3 weeks at 120 mg/ day, received an intravenous drip infusion of 90 mg/body of CDDP on day 8, and then discontinued chemotherapy for 2 weeks, which was regarded as one course. After 2 courses of the chemotherapy, an upper gastrointestinal endoscopy showed that the primary tumor was reduced in size, the periphery of the tumor almost flattened, and an abdominal CT scan confirmed the loss of swelling in the periaortic lymph nodes. The responsive rate was evaluated as PR. Since a radical resection was considered possible, we performed a total gastrectomy with complete D3 extirpation combined with a splenectomy. Histological efficacy was evaluated as grade 2 in primary cancer, and grade 3 in lymph nodes. Regrettably, the patient died one year and 7 months postoperatively. However, we consider the TS-1 and CDDP in combination useful as preoperative chemotherapy for advanced gastric cancer with periaortic lymph node involvement.     

A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP as neoadjuvant chemotherapy

A 64-year-old male visited our hospital with complaints of epigastric pain. Computed tomography (CT) showed gastric cancer with extensive paraaortic lymph node metastasis. We decided that a curative operation was impossible, and administered the following chemotherapy. After 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks with 90 mg of CDDP was administered intravenously on day 8, CT showed a 90.6% reduction in the paraaortic lymph node metastasis. No serious adverse reaction was observed. After 2 courses of this chemotherapy, surgery was performed after informed consent was obtained from the patient. Histrogical result showed PR. The patient is now healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful for advanced gastric cancer.     

Two cases of advanced gastric cancer responding to TS-1: a novel oral formation of 5-fluorouracil

TS-1, a novel oral formation of 5-fluorouracil, consists of 1 M tegafur (5-FU), 0.4 M CDHP and 1 M Oxo. The response rate in the late phase II study was reported as 49% in the patients with advanced gastric cancer. We report two patients with metastases from gastric cancer who markedly responded to TS-1. CASE 1: A 74-year-old man who suffered abdominal tumor was admitted to our hospital. Computed tomography (CT) showed advanced gastric cancer with huge liver metastases and extensive lymph node metastases. After 120 mg of TS-1 was orally administered for 12 weeks, CT showed a 77% reduction in the liver metastases. No serious adverse reactions were observed. CASE 2: A 66-year-old man had undergone a curative distal gastrectomy with D2 lymphadenectomy. One year later, CT showed enlargement of paraaortic lymph nodes due to cancer recurrence. There were no metastatic lesions in the other organs. After 100 mg of TS-1 was orally administered for 4 weeks, CT revealed that almost complete reduction of the metastatic nodes was obtained. Adverse reactions at grade 2 for leucopenia and anemia were observed. In conclusion, TS-1 was effective and well tolerable for patients with advanced gastric cancer.     

A case of advanced gastric cancer treated with paclitaxel and TS-1

We treated a case of advanced gastric cancer with paclitaxel and TS-1. A 64-year-old man underwent total gastrectomy, splenectomy, and D2 + No. 16 a 2, b 1 lymph node (LN) dissection for gastric cancer. Computed tomography (CT) revealed metastases of supraclavicular and para-aortic LNs in the 4th postoperative month. Paclitaxel 90 mg was infused once a week, and TS-1 100 mg was administered daily. One course consisted of infusion of paclitaxel for 3 weeks followed by 2 weeks rest and administration of TS-1 for 4 weeks followed by 2 weeks rest. At the end of 4 courses of paclitaxel and 3 courses of TS-1, a partial response of the supraclavicular LN metastasis and a complete response of the para-aortic LN metastasis were achieved. There were no remarkable side effects for 2 years after the operation. This chemotherapy might be suitable to treat patients with LN metastases of advanced gastric cancer.     

A case of advanced gastric cancer--efficacy of combination therapy of doxifluridine and weekly paclitaxel

A 65-year-old man underwent distal gastrectomy for advanced gastric cancer. Histological examination revealed that a lymph node metastasis extended to the para-aortic nodes. After operation, he was treated with TS-1 as first-line chemotherapy. After 10 months of the first-line chemotherapy, the lymph node swelling increased in size, and new lesions were detected. Then, the patient was treated by combination therapy of doxifluridine and weekly paclitaxel. Weekly paclitaxel administration (PTX 80 mg/m(2), 2 consecutive weeks, 1 week break) and oral administration of doxifluridine (600 mg/m(2), 14 consecutive days) were performed as the second-line chemotherapy. After 2 courses, abdominal CT scan showed a remarkable reduction of the para-aortic lymph nodes. The second-line chemotherapy was continued until the 7th course, then stopped without progression of the disease, and the patient maintained good quality of life. PTX/5'-DFUR combination therapy was thought to be an effective chemotherapy for advanced gastric cancer.     

A case of stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy

We report herein a case with stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy. A 65-year-old female was diagnosed as having type 3 gastric cancer with para-aortic lymph node metastases. She underwent total gastrectomy with extended lymph node dissection on March 2003. Histopathological examination revealed that the tumor was poorly-differentiated adenocarcinoma with para-aortic lymph nodes metastases and completely resected.After the operation,she was treated by adjuvant chemotherapy with TS-1. In March of 2004, she suffered from hematuria, and a CT scan revealed para-aortic lymph nodes metastases and left kidney metastasis. Then, she was treated by a weekly infusion of paclitaxel as second-line chemotherapy. After 3 courses, the tumor disappeared and efficacy was judged as CR. Moreover, CR was maintained after 7 courses. At this writing in January of 2005, she is well and has been treated with paclitaxel without any severe adverse events. Therefore, weekly paclitaxel therapy was considered to be one of the promising second-line chemotherapies for advanced or recurrent gastric cancer previously treated by TS-1.     

A case of recurrent pleural effusion and positive cytology of advanced gastric cancer treated by TS-1 plus weekly taxane as second-line chemotherapy

A second-line chemotherapy for advanced gastric cancer has not been established. We report a case of good response in a 39-year-old woman who had recurrent pleural effusion and positive cytology of type 4 gastric cancer and was treated with TS-1, a DPD inhibitory fluoropyrimidine, in combination with weekly taxane. After a partial response for type 4 gastric cancer from the treatment with 2 courses of TS-1 plus low-dose cisplatinum (CDDP), followed by outpatient chemotherapy with TS-1 alone or TS-1 plus weekly CDDP, left pleural effusion appeared and CA19-9 increased during the 7th course of the chemotherapy. Cytology of the effusion was class IV. The patient was treated with a course of TS-1 (120 mg/day, day 1-21) plus paclitaxel (50 mg/m2, day 1, 8) followed by 2 week washout. In the following courses, paclitaxel was replaced with docetaxel (30 mg/m2, day 1 and 8) and the course was continued in the outpatient setting. After 2 courses, the left pleural effusion disappeared and remained absent after 6 courses. Gastric biopsy showed no cancer cells and abdominal CT showed no recurrence. Serum CA19-9 doubled 1 week after taxane treatment and decreased gradually week by week during the course. This case suggests that a combination of TS-1 and taxane is effective against recurrent pleural effusion of advanced gastric cancer and useful as a second-line chemotherapy.     

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 metastatic esophageal cancer responding remarkably to combination chemotherapy of TS-1 and cisplatin

A 51-year-old male patient with esophageal cancer and cervical, thoracic and celiac artery lymph node metastases was treated by combination chemotherapy of TS-1 and cisplatin. TS-1 (80 mg/m2/day) was administered for 14 days followed by 14 days rest as 1 course. Cisplatin (70 mg/m2/day) was administered in 24-hour continuous intravenous infusion at day 8 after the start of TS-1. Before treatment, the tumor marker, CEA showed 27,060 ng/ml. After 5 courses of chemotherapy, endoscopy revealed that the primary tumor had disappeared and no cancer cells were detected by endoscopic biopsy. Chest and abdominal CT scan also showed almost total disappearance of the lymph nodes metastases. CEA decreased to 710 ng/ml. No high-grade toxicities (WHO grade 3 or 4) were seen during the chemotherapy. He is now very well. This TS-1/cisplatin chemotherapy regimen might be a useful treatment for metastatic esophageal cancer.     

A successful case of liver metastasis from gastric cancer treated with S-1 + induced hypertensive hepatic arterial infusion chemotherapy--a case report

We have experienced a successful case of liver metastasis from gastric cancer treated with S-1 plus induced hypertensive hepatic arterial infusion chemotherapy. A 50-year-old man had undergone distal gastrectomy with extended lymphadenectomy for advanced gastric cancer. Although he was given 100 mg/day of S-1 for postoperative adjuvant therapy, an abdominal CT scan showed a liver metastasis at the hepatic segment 6 after 3 courses of adjuvant chemotherapy. Then, intra-arterial hepatic cannulation connecting to a subcutaneously implanted port system was indwelt via left subclavial artery. Mitomycin C (10 mg) was injected through out the induced hypertension with intravenously-administered angiotensin II once a month. After he received three courses of this combination chemotherapy, the liver metastasis has disappeared on CT scan and a complete response (CR) has been maintained.