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 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 multiple bone metastasis from gastric carcinoma given chemotherapy with TS-1 combined with cisplatin

We experienced a case of bone metastatic recurrence from gastric carcinoma that responded to TS-1 combined with low-dose cisplatin (CDDP) therapy. A 63-year-old male patient presented with multiple bone metastases 5 years after radical surgery for advanced gastric carcinoma. The titer of serum CEA showed extremely high levels of 18,000 ng/ml. The uptake area was found at all vertebrae, ribs, and pelvis by scintigraphy 99mTc-HMDP. The chemotherapy regimen, performed in the outpatient clinic, comprised daily oral administration of 80 mg/m2 of TS-1 for 14 days and CDDP 20 mg/m2 infusion (day 1). This regimen was repeated every 3 weeks for 9 months. After that, severe pain diminished and the titer of serum showed CEA had improved to 599 ng/ml. The uptake at the multiple bone metastasis was found to have decreased by scintigraphy. The patient was able to resume his full social activities. TS-1/low-dose CDDP therapy seems to be applicable for the treatment of gastric carcinoma with bone metastasis.     

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 report of advanced gastric cancer responding to TS-1, a novel oral fluorouracil derivative

TS-1 is a new, oral anticancer agent composed of two modulators, gimeracil (CDHP) and oteracil potassium (Oxo) are mixed with tegafur in a ratio of 1:0.4:1. We report one case of advanced gastric cancer with lung and lymph node metastases that completely responded to TS-1. A 71-year-old woman was admitted to our hospital because of breathlessness. A diagnosis of advanced gastric cancer with extensive lymph node metastases and multiple pulmonary metastases was made. One hundred mg/body/day of TS-1 was orally administrated for 4 weeks. A partial response (PR) was obtained after the first course with regression of multiple pulmonary metastases. After 1 drug-free week, the second course was administered with 120 mg/body/day of TS-1 for 4 weeks. After two courses, the primary tumor was reduced to an ulcer scar with pathological confirmation of a complete disappearance of the cancer tissue. Moreover, computed tomography (CT) showed a complete regression of the extensive lymph node and diffuse lung metastases, for a complete response (CR). The serum level of CEA was reduced from 172.7 ng/ml to 8.1 ng/ml after TS-1 treatment. As for adverse events, only pigmentation of the skin and Grade 2 oral aphta were observed.     

Combination chemotherapy of TS-1, docetaxel and CDDP produces a remarkable response in a patient with advanced esophageal cancer

We report a patient with advanced esophageal cancer who achieved a complete response to combination chemotherapy of TS-1, docetaxel and CDDP. A 74-year-old man was admitted to our hospital for advanced esophageal cancer with a complaint of dysphagia. He received chemotherapy, consisting of TS-1 100 mg/body, docetaxel 35 mg/m(2), and CDDP 10 mg/m(2), every 3 weeks. TS-1 was administered for 14 days followed by 7 days rest; docetaxel and CDDP were administered by intravenous infusion at day one and day 8 after beginning TS-1. After three cycles of chemotherapy, his dysphagia disappeared, and endoscopic examination of the primary esophageal tumor showed a complete response. Endoscopic examination with biopsy confirmed the disappearance of the esophageal cancer. No severe side effects were observed during this chemotherapy. Combination chemotherapy of TS-1, docetaxel, and CDDP can thus be effective for advanced esophageal cancer.     

Remarkable response of simultaneous advanced esophageal and gastric cancer to combined chemotherapy with weekday-on/Weekend-off TS-1 plus biweekly cisplatin

A 66-year-old man was found to have both advanced cancer of the middle thoracic esophagus and advanced cancer of the middle third of the stomach with paraaortic lymph node metastases. The prognosis was poor because of local advanced disease and distant metastasis. The patient was therefore given combined chemotherapy with TS-1 and cisplatin. TS-1 (80 mg/day) was administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 (weekday-on/weekend-off schedule), and cisplatin (70 mg/m2 intravenously over the course of 2 hours) was administered on days 1 and 15 of a 28-day cycle. After 2 courses of chemotherapy the esophageal lesion had a complete response, and the gastric lesion had a partial response (reduction ratio, 71.4%). However, stomatitis and anorexia of grade 2 (NCI-CTC) occurred. Two courses of TS-1 alone (80 mg/m2) were therefore given. The esophageal lesion continued to show a complete response and the gastric lesion a partial response (reduction ratio, 85.7%). There was no change in the para-aortic lymph node metastasis (No. 16a2 latero). No adverse reaction to chemotherapy was severer than grade 3, and a good response was obtained. These findings indicate that chemotherapy with a combination of TS-1 and cisplatin is effective against advanced esophageal cancer and 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 producing alpha fetoprotein with multiple liver metastases responding to TS-1 after TAE]

We report a case of advanced gastric cancer producing Alpha Fetoprotein (AFP) with multiple liver metastases in which TS-1 is effective. Prognosis of gastric cancer producing AFP is well known to poor. A 74-year-old female was admitted complaining of anemia. She was diagnosed as having advanced gastric cancer with multiple liver metastases producing AFP by endoscopy, computed tomography and angiography. Her serum AFP level was 17,666 ng/ml and her serum CEA level was 5-2 ng/ml. After transarterial embolization (TAE), her family rejected her operation because it would not be curative. So, she was treated with TS-1, 40 mg, administered orally every day, followed by 14 days rest, as the first course. The next was TS-1, 80 mg orally administered for 6 courses. Her serum AFP level was down from 17,666 ng/ml to 94 ng/ml after 6 courses of TS-1. CT revealed that liver metastases did not change and endoscopy showed the primary lesion has diminished. Our report is the first to demonstrate that TS-1 is effective for patients with advanced gastric cancer producing AFP with multiple liver metastases.     

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 esophageal cancer treated by combined chemotherapy of TS-1 and CDDP with radiotherapy

A 70-year-old patient with advanced esophageal cancer with invasion to the aorta was treated by combined chemotherapy of TS-1 and CDDP with radiotherapy. TS-1 (80 mg/m2) was administered for 14 days followed by 14 days rest, CDDP (70 mg/m2) was administered by 24 h continuous intravenous infusion at day 8 after the start of TS-1. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy for 3 weeks. After the end of the first course, leukocytopenia of grade 2 and thrombocytopenia of grade 2 were observed. The second course of chemoradiotherapy was suspended for 1 week. After recovery from the toxicity, the second course was started. After the 2 courses of chemoradiotherapy, endoscopic examination with biopsy revealed the disappearance of the esophageal cancer. Combined chemotherapy of TS-1 and CDDP was administered 2 times after chemoradiotherapy. After this therapy, endoscopy and a CT showed a complete clinical response. No severe adverse effects were observed during this therapy. Combined chemotherapy of TS-1 and CDDP with radiotherapy can be effective for advanced esophageal cancer.     

A case of recurrent advanced gastric cancer suggesting the efficacy of TS-1 and CDDP combination chemotherapy

The patient, a 53-year-old male, underwent radical surgery for advanced gastric cancer (stage IV). On the second day after surgery, adjuvant chemotherapy consisting of 250 mg/day 5-FU (i.v.) for 14 days, followed by 450 mg/day of UFT-E for about 12 months, was initiated. About 21 months after surgery (7 months after cessation of medication), the CA19-9 level had risen (136 U/ml). After 26 months, the patient experienced a backache and his CEA and CA19-9 levels had risen 11.7 ng/ml and 869 U/ml, respectively. The results from an imaging examination were suggestive of multiple bone metastases and para-aortic lymphatic metastasis. Chemotherapy was resumed with only TS-1 (100 mg/day). Because the tumor markers (TM) continued to rise, he was hospitalized and the medication was combined with daily administration of 10 mg of CDDP (TS-1 + CDDP protocol). When the total dose of CDDP reached 160 mg, there was a dramatic drop in the TM (surrogate marker) level. The patient was discharged and medication of TS-1 and 10 mg/day of CDDP twice a week was continued on an outpatient basis. Five months after the initial administration of FP, the CEA and CA19-9 returned to normal levels (4.3 ng/ml and 33 U/ml, respectively). Metastases to the para-aortic lymph nodes had disappeared and the sites of bone metastases were reduced in size. The patient was able to resume his full social activities. Since that time, a second-line therapy has been added. Currently (about two years after the recurrence), he is still undergoing therapy with TS-1 + CDDP.     

A case of advanced gastric cancer with multiple liver metastases successfully treated with TS-1/low-dose CDDP/lentinan combination chemotherapy

We report herein a case of advanced gastric cancer successfully treated with TS-1/low-dose CDDP/Lentinan combination chemotherapy. A 74-year-old male suffering from anorexia was admitted to our hospital and diagnosed as having type 2 gastric cancer metastasizing to the liver. TS-1 was orally administered at 100 mg/body/day for 28 days with a 14-day interval as one session. During the second session, because grade 1 thrombocytopenia was noted, administration of TS-1 was rescheduled to every other day. CDDP was infused at 10 mg/body/day on day 6 to 10, 13, 15, and 17. After his discharge, CDDP at 10 mg/body and Lentinan at 2 mg/body were weekly infused as ambulant patient chemotherapy. The abdominal CT scan showed reduction of hepatic tumors by 86% in three months and 97% in 16 months. Metastatic lymph nodes disappeared in 4 months. The primary tumor was reduced and flattened to a cicatrix, and endoscopic biopsy revealed no cancer cells. The tumor markers, CEA (716.9 ng/ml) and CA 19-9 (57.2 U/ml), were reduced to normal range. The therapeutic efficacy was judged as a partial response (PR), which lasted for 16 months without severe adverse effects. He maintained good quality of life. This combination chemotherapy was thought to be beneficial for patients with advanced gastric cancer.     

A case of advanced gastric cancer treated by TS-1 for 3 years and 7 months

A 72-year-old man was diagnosed as gastric cancer with pyloric stenosis by an upper gastorintestinal endoscopy for anemia in July 2001. Computed tomography (CT) of the abdomen showed multiple liver metastases. Serum CEA was 6.2 ng/ml. At laparotomy to improve anemia and pyloric stenosis in September 2001, lymphnode metastases invaded the stomach and the pancreatic body. Gastro-jejunostomy was performed without gastrectomy. Oral administration of 100 mg of TS-1 for 28 consecutive days followed by a 14-day rest was given postoperatively. The response assessment of chemotherapy after 1 year was no change (NC) of the primary lesion on endoscopic examination, and liver metastases showed a partial response (PR) on CT. Serum CEA was raised to 86.1 ng/ml in April 2004. The treatment was changed to weekly paclitaxel. The patient died in July 2005. This case with unresectable gastric cancer had been treated by oral administration of TS-1 as an outpatient for 3 years and 7 months.     

A case of adenosquamous gastric carcinoma successfully treated with TS-1, low-dose CDDP and docetaxel as neoadjuvant chemotherapy

The patient was a 66-year-old male with extremely advanced gastric cancer type 3 and diagnosed with adenocarcinoma by endoscopic biopsies specimens. Combined chemotherapy of TS-1, CDDP and docetaxel was prescribed in order for tumor reduction and downstaging. TS-1 (80 mg/m(2)) was administered 28 days followed by 14 days rest as one course. CDDP (8 mg/m(2)) was administered on days 1, 2, 14 and 15 and docetaxel (40 mg/m(2)) was administered on day 1 and 14, followed by 4 weeks rest as one course. After 2 courses of treatment, a CT scan revealed a minor response of tumor reduction. Therefore, total gastrectomy, partial pancreas body and tail resection, and D 2 lymph node dissection were performed. The patient had undergone adjuvant chemotherapy of TS-1 and biweekly docetaxel after surgery with no recurrence for 13 months. Adverse reactions were grade 3 neutropenia and grade 2 diarrhea. Combined chemotherapy of TS-1, low-dose CDDP and docetaxel were intensive and required constant patient monitoring. However, it proved effective and feasible as a neoadjuvant chemotherapy regimen for advanced 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 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.     

A case of rectal cancer with multiple liver metastases responding to TS-1

A 63-year-old woman was referred to our hospital with complaints of anal pain, constipation and abdominal distention caused by a rectal tumor. After examinations, she was diagnosed as rectal cancer with multiple liver metastases. The CEA level was 70.0 ng/ml and the CA19-9 level was more than 5,000 U/ml at admission. To prevent bowel obstruction, low anterior resection of the rectum was performed. At 34 days after operation, TS-1 chemotherapy was started as outpatient treatment (each course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the CEA level was reduced to 3.3 ng/ml and the CA19-9 level to 15 U/ml, both under the normal value. After the second course, administration was discontinued due to diarrhea, and restarted as a daily oral administration of 80 mg TS-1. After the five courses, the CEA level was 4.0 ng/ml and the CA19-9 level was 4 U/ml, both under the normal value. Multiple liver metastases had remarkably reduced in the CT findings. The patient continues to undergo outpatient treatment with good QOL.     

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 peritoneal dissemination of gastric cancer successfully treated by irinotecan combined with cisplatin

We report a case of a 59-year-old man with advanced gastric cancer. Distal gastrectomy with lymph node dissection (D1) was performed. Pathological staging was IV (T3N1CY1), and the operation resulted in curability C. The serum CA19-9 level before the operation was 201 U/ml, and it did not normalize 3 months after the operation. Postoperative chemotherapy (TS-1, 100 mg/day) was performed. Because the tumor markers such as CEA and CA19-9 level elevated 5 months after the operation, triweekly docetaxel therapy and TS-1 administration (days 1-14) were performed. We disbontinued this therapy after 2 courses due to adverse reactions, such as leukopenia (grade 4) and liver dysfunction (grade 2). Peritoneal dissemination was diagnosed by the appearance of ascites and thickness of the peritoneum 11 months after the operation. So the patient was treated with a biweekly combination chemotherapy of irinotecan (CPT-11 60 mg/m2) and cisplatin (CDDP 30 mg/m2). Eight courses of this therapy induced partial remission and normalization of the serum CEA level. No major adverse reaction to this therapy was observed. The partial remission and good patient's QOL were achieved during follow-up 7 months after the administration of CPT-11 plus CDDP. This case suggests that patients with recurrent peritoneal dissemination of gastric cancer could benefit from CPT-11 with CDDP combination therapy as a second-line or third-line treatment.