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.     

Stage IV gastric cancer patient who underwent palliative gastrectomy showing complete response to induction therapy with methotrexate plus 5-fluorouracil and secondary treatment with oral TS-1

We describe our experience with a patient who had undifferentiated gastric carcinoma with extensive lymph node metastasis, including para-aortic lymph-node metastasis, and had a complete response to induction therapy with methotrexate plus 5-fluorouracil (sequential therapy with MTX, 5-FU, and Leucovorin) and secondary treatment with oral TS-1. The patient was a 71-year-old woman with a massive gastric tumor (signet ring cell carcinoma), occupying most of the stomach. A computed tomographic (CT) scan revealed para-aortic, celiac, and common hepatic lymph-node metastases. Stage IV disease was diagnosed. Palliative total gastrectomy was performed to control bleeding and to improve oral intake of food. Two courses of induction therapy with MTX, 5-FU, and Leucovorin were started 3 weeks after surgery. A CT scan revealed residual lymph node metastasis. The response was assessed to be no change, but the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 improved from 7,028 ng/ml and 726 U/ml 3 weeks after surgery to 2,832 ng/ml and 281 U/ml, respectively. Secondary treatment with oral TS-1 was begun, and a CT scan showed distinct shrinkage of lymph-node metastases. There was no serious toxicity. The levels of CEA and CA19-9 decreased markedly to 2.9 ng/ml and 16 U/ml, respectively, about 6 months after surgery and remained at 3.7 ng/ml and 16 U/ml, respectively, about 1 year after surgery.     

A case of transverse colon cancer with left supraclavicular lymph node metastasis and paraaortic lymph node metastases responding to TS-1

A 61-year-old man was seen at our hospital because he noticed a mass on the left side of his neck. After examinations, he was diagnosed as transverse colon cancer with the left supraclavicular lymph node metastasis and paraaortic lymph node metastases. Rt. hemicolectomy was performed for the transverse colon cancer. At 15 days after operation, TS-1 chemotherapy was started (each treatment 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 left supraclavicular lymph node had shrunk markedly in physical findings. After the second course, both the left supraclavicular lymph node metastasis and paraaortic lymph node metastases had disappeared in CT findings. A complete remission was observed after the second course, and was maintained thereafter. The serum level of CA 19-9 decreased from 62 U/ml under the normal value after the second course, and was kept under this normal value. Leukopenia and eruption (grade 2) were the only observed adverse effects. This patient continues to undergo outpatient treatment with good QOL.     

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

We report the case of a 58-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases, which responded to chemotherapy using TS-1. The patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks rest as 1 cycle. After 4 cycles, most of the liver metastases had disappeared and serum CEA level was reduced from 140 to 53.9. The patient received chemotherapy at our outpatient clinic for 9 months during which time there was no regrowth after the first treatment. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of advanced gastric cancer.     

A case of liver metastasis of gastric cancer responding well to TS-1

We report the case of a 79-year-old female with gastric cancer accompanied by liver metastasis that was successfully treated by TS-1, a novel oral fluoropyrimidine derivative. Abdominal CT scan showed a low-density area in the lateral segment of the liver and lymph node swelling in the right side of the abdominal aorta. One treatment course consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. After 2 courses of this treatment, an abdominal CT scan showed no evidence of liver metastasis and a reduction of lymph nodes metastasis. The serum level of CA19-9 was reduced from 780 U/ml to within a normal range. Grade 1-2 toxicity (nausea and diarrhea) was seen after 2 courses. We conclude that TS-1 may be beneficial in the treatment of the liver metastasis of gastric cancer.     

A case report--Efficacy of combination therapy to unresectable advanced gall bladder carcinoma--palliative operation, hepatic arterial infusion therapy, and radiation therapy

A patient of advanced gall bladder carcinoma with liver metastases and direct invasions to the duodenum and liver underwent a palliative operation, 3 hepatic arterial infusion (HAI) therapies, and radiation therapy at the obstructive common biliary duct. (Palliative operation was a partial resection of duodenum and transverse colon, HAI therapy with 5-FU (1 g/day) was given as a continuous infusion for 6 days, radiation therapy was given 2 Gy/day for 20 times) After the combination therapy, the main tumor of gall bladder and hepatic metastases were decreased and tumor markers were normalized. (CEA 15.1 ng/ml, CA19-9 93 U/ml to CEA 4.4 ng/ml, CA19-9 29 U/ml) Then, an expandable metallic stent (EMS) could be inserted to the stenotic common biliary duct after radiation therapy. Although para-aotic lymph nodes were existent, systemic chemotherapy (UFT 300 mg/day p.o., MMC 2 mg/week div) has been performed as an outpatient with a good quality of life.     

A case of paraaortic lymph nodes metastases responding to TS-1 following surgery for gastric cancer

A 58-year-old man underwent distal gastrectomy with a D2 lymph adenectomy for advanced gastric cancer (pStage IIIB). Seven months later, abdominal CT revealed multiple paraaortic lymph nodes metastases. Radiation therapy was not effective, so TS-1 chemotherapy was started (each treatment course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). The CT findings revealed that the metastatic lesion had shrunk markedly after the first course. A complete response was observed after the fifth course, and was maintained thereafter. The serum level of CEA decreased from 337 to 2.7 ng/ml after the third course, but gradually rose again and stayed between 30 and 50 ng/ml. Although the re-elevation of serum CEA level suggested the existence of a recurrent lesion, no sign of recurrence was found by radiographical or endoscopic examinations. Leukocytopenia and anemia (grade 2) were the only observed adverse effects. This patient continues to undergo outpatient treatment with good QOL.     

A case report of poorly-differentiated adenocarcinoma in sigmoid colon cancer with liver and pulmonary metastasis responding to TS-1 and CPT-11

A 66-year-old woman (156 cm, 58 kg) underwent sigmoid colectomy for cancer. She was found to have simultaneous liver and peritoneal metastases at operation, which had not been detected with CT examination before operation. After operation, CT showed multiple liver metastasis and a high level of CEA and CA19-9 . Pathological findings were type 3, 30 x 20 mm, poorly-differentiated adenocarcinoma, se, ly 2, v 2, n 2 (+), ow (-), aw(-), H 3, P 0 (stage IV). Treatment of the patient consisted of daily oral administration of 80 mg TS-1 for 21 days and 60 mg CPT-11 on 1 day and 15 day as one course.After 2 courses, tumor sizes of liver metastases and the level of tumor markers became reduced.The current case suggested that the administration of TS-1 and CPT-11 may have a potent therapeutic efficacy in advanced colorectal cancer.     

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

The patient was a 61-year-old man who was referred to our hospital with a complaint of epigastric pain. Upper gastrointestinal endoscopy and X-ray examination of the stomach revealed type 3 cancer in the gastric antrum, extending to the middle body. It was about 9 cm in diameter, and the biopsy specimen revealed moderately differentiated tubular adenocarcinoma. Abdominal CT scan showed marked enlargement of No. 3 lymph nodes along the lesser curvature of the stomach. Examination of the blood showed a hemoglobin of 10.2 g/dl, CEA 5.8 ng/ml, CA19-9 330.5 U/ml. For this gastric cancer, clinical Stage IIIA (cT3N1HOPOMO), neoadjuvant chemotherapy with TS-1/CDDP was planned. TS-1 (120 mg/day) was orally administered for 3 weeks followed by a drug-free-2-week period as the first course, and 93 mg (60 mg/m2) of CDDP administered by intravenous drip on day 8. There were grade 2 nausea and grade 3 appetite loss by intravenous administration of CDDP in the second course. An upper GI series revealed 33% reduction of gastric cancer, and laboratory studies CEA and CA 19-9 showed normal values. One month after the second course of chemotherapy, total gastrectomy, splenectomy and lymph node dissection D2 were performed. The pathological specimens showed no cancer cells in the surgically obtained stomach and lymph nodes, so the histological effect was Grade 3. The postoperative course was satisfactory, and he now attends outpatient department without any findings of recurrence 12 months after the operation. TS-1/CDDP chemotherapy produced a high response in this case, and it may be useful as neoadjuvant chemotherapy for advanced gastric cancer.     

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.     

A case of advanced pancreatic cancer with multiple liver metastasis that improved remarkably with use of low-dose cisplatin and TS-1

The prognosis and QOL of unresectable pancreatic cancer are very poor. A symptomless 60-year-old male was admitted for examination of a high serum CA19-9 level. Following ultrasound and abdominal CT, we diagnosed unresectable advanced pancreatic cancer with multiple liver metastasis. After we obtained his informed consent, we administered continuous infusion of 5-FU and low-dose cisplatin (CDDP) infusion (low-dose FP therapy) for 3 weeks. He then underwent combination chemotherapy with low-dose CDDP and TS-1 on an outpatient basis. During the chemotherapy, he did not experience any major adverse event and his QOL was relatively good. On follow-up CT 3 months later, the primary tumor in the pancreas was found to be stable. However, the size and number of liver tumors were remarkably reduced. The serum CA19-9 level had also remarkably decreased from 48,300 U/ml to 1,480 U/ml. In conclusion, the combination chemotherapy using low-dose CDDP and TS-1 can be effective in cases of unresectable pancreatic cancer with multiple liver metastasis.     

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.     

A case of recurrent stomach cancer treated with 5-fluorouracil responding to weekly paclitaxel therapy

We report a patient with unresectable stage IV stomach cancer with metastasis to the paraaortic lymph nodes who achieved an effective response to neoajuvant chemotherapy, which allowed curability-B resection, and in whom weekly paclitaxel (TXL) therapy for postoperative recurrence was very effective in improving QOL. The patient was a 65-year-old man. After preoperative PMFE therapy, CEA decreased from 68.1 ng/ml to 0.8 ng/ml, and CA19-9 from 15,000 U/ml to 190 U/ml. The paraaortic lymph nodes disappeared, and stomach wall thickening decreased. The overall response to treatment was evaluated as a partial response (PR). After surgery, the patient was given TS-1, but became unable to take oral medication because of retroperitoneal and lymph node recurrence. Since the cancer appeared to be resistant to 5-fluorouracil (5-FU), the patient was treated by weekly TXL therapy. Increased appetite and weight gain were observed from the middle of the first course of therapy, and CEA decreased from 28.2 ng/ml to 4.9 ng/ml, and CA19-9 from 15,000 U/ml to 2,000 U/ml. Abdominal CT scans demonstrated shrinkage of the tumor. Although the patient died 1 year and 8 months after the initial examination, he was able to take oral medication and maintain good QOL for 10 months after the start of TXL therapy. Only grade 1 side effects (alopecia and leukopenia) were observed throughout the course. These results suggest that TXL therapy is effective also for 5-FU-resistant stomach cancer, and exhibits effects early even in patients in a poor general condition, causing only mild side effects, with early improvements in QOL.     

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 stage IV gastric cancer with multiple liver metastases and carcinomatous ascites responding to TS-1 for six months before progression

We report the case of a 72-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases and carcinomatous ascites which responded to chemotherapy using TS-1. Treatment of the patient with daily oral administration of 120 mg TS-1 for 4 weeks resulted in complete regression of the liver metastases and ascites, as well as a 35% reduction in the size of the primary lesion. After 2 cycles, the primary tumor size was reduced to 55% and serum CA19-9 and CA125 levels were decreased to the normal ranges. This regimen was effective without any adverse effects, and improved the patient's QOL, for 6 months before progression of liver lesions. The patient received chemotherapy at our outpatient clinic for 10 months after the first treatment, after which he died of peritonitis carcinomatosa. The current case suggests that TS-1 may have a potent therapeutic efficacy in advanced gastric cancer patients.     

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.     

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.     

Meningeal carcinomatosis preceded by a rapid increase in serum CA19-9 levels in a patient with breast cancer

We report a patient with breast cancer who developed meningeal carcinomatosis that was preceded by a rapid increase in the serum level of carbohydrate antigen (CA) 19-9. A 60-year-old woman was admitted for primary breast cancer with multiple metastases to the vertebrae. She received cyclophosphamide 400 mg/m², epirubicin 40 mg/m², and 5-fluorouracil (5-FU) 400 mg/m² (CEF) chemotherapy every 3 weeks. Upon admission, her serum concentrations of carcinoembryonic antigen (CEA) and CA19-9 were 28.6 ng/ml and 99.2 U/ml, respectively. After three cycles of CEF therapy, her serum CEA decreased, and metastases to the vertebrae were attenuated. Her serum CA19-9 rapidly increased, however. A modified radical mastectomy was performed, but her serum CA19-9 levels still remained high (>500 U/ml). After four cycles of CEF therapy, she experienced headaches and vomiting due to an increase in cerebrospinal pressure, and she was diagnosed with meningeal carcinomatosis. At the time of this diagnosis, the concentration of CA19-9 in her cerebrospinal fluid was greaterthan 500 U/ml, and immunohistochemical examinationrevealed that carcinoma cells in the cerebrospinal fluid overexpressed CA19-9. To our knowledge, this is the first report of the development of meningeal carcinomatosis from CA19-9-producing breast cancer cells, showing thatCA19-9 expression was associated with breast tumorprogression.     

An autopsy case of a gastric cancer associated with elevated AFP, CEA and CA19-9

A 48-year-old male developed gastric cancer (Borrmann III) with lung and liver metastases. Laboratory examination revealed a markedly elevated AFP (24, 241 ng/ml), CEA (9739.8 ng/ml), and CA-19-9 (726U/ml). Nevertheless, he underwent a subtotal gastrectomy for the hemostasis of a bleeding malignant lesion. Histological examination showed a moderately differentiated adenocarcinoma. A PAP for an AFP and a CEA disclosed positive staining. In addition, An autopsy revealed metastases to the liver and lungs with a positive result of PAP for AFP and CEA. Further, CA19-9 also was confirmed weakly in these same tissues, histochemically. Therefore this gastric cancer was considered an AFP, CEA, and CA19-9-producing tumor. Gastric cancer with 3 elevated tumor markers in the same patient is rare and its mechanism may elucidate the origin of gastric cancer and the resulting differentiation in the foregut.     

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.