A case of hepatocellular carcinoma with bone metastasis responding to concurrent TS-1/low-dose cisplatin (CDDP) therapy and radiotherapy

A standard treatment for hepatocellular carcinoma with extrahepatic metastasis is not established and chemotherapy is ineffective. We experienced a case of hepatocellular carcinoma with bone metastasis that responded to concurrent TS-1/low-dose cisplatin (CDDP) therapy and radiotherapy. A 58-year-old male patient with left iliac bone metastasis after 2 hepatectomies was admitted to our hospital. The titer of serum AFP and PIVKA-II showed an extremely high levels, 12,350.5 ng/ml and 993 mAU/ml, respectively. The uptake area was found at the left iliac bone by scintigraphy with 99mTc-HMDP. Treatment with TS-1/low-dose CDDP therapy and radiotherapy (36 Gy) was started concurrently. The chemotherapy regimen comprised daily oral administration of 100 mg of TS-1 for 21 days and CDDP 10 mg/body infusion (day 1-5, 8-12). An additional 2 courses of TS-1/low-dose CDDP therapy were repeated. After that, severe pain diminished and the titer of serum showed AFP and PIVKA-II had improved to within normal ranges. The uptake at the left iliac bone was found to have decreased by scintigraphy. Adverse events were grade 1 nausea and leucopenia. TS-1/low-dose CDDP therapy seems to be applicable for the treatment of hepatocellular carcinoma with bone metastasis.     

A case of gastric cancer with multiple bone metastasis that responded to S-1 with low-dose cis-platinum

We report a patient with multiple bone metastasis who was treated successfully using S-1 and low-dose cis-platinum (CDDP). Metastasis was diagnosed 4 years after distal gastrectomy for early gastric cancer in a woman now 68 years old. Surgery was performed on February 9, 1999. The primary tumor was located in the midportion of the gastric body, and had invaded the submucosa with metastasis to lymph nodes in the area of the lesser curvature. She was discharged from our hospital 24 days after surgery. About 4 years after surgery, she experienced a backache and her CEA and CA19-9 levels had risen to 15.30 ng/mL and 996.5 U/mL, respectively. The results of an imaging examination were suggestive of multiple bone metastasis. Treatment with S-1+CDDP was started with the following regimen: daily oral administration of 100 mg/body/day S-1 for 14 days, followed by a 7-days rest and CDDP 20 mg/body infusion on day 1 and 8. Three months after initiation of therapy, the CEA and CA19-9 levels decreased 2.80 ng/mL and 36.8 U/mL, respectively. No severe adverse effects were observed with this therapy. The combination of S-1 and CDDP can be a good tool for the management of gastric cancer with bone metastasis.     

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 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.     

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 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 patient with gastric cancer complicated with severe DIC and multiple bone metastasis showing a high response to combination of TS-1 and CDDP

We report a 48-year-old male with gastric cancer who was suffering from acute onset of DIC due to multiple bone metastases. Treatment with TS-1 + CDDP was started with the following regimen: daily oral administration of 80 mg/m2 TS-1 for 21 days, followed by a 14-day rest and CDDP 60 mg/m2 infusion on day 8. The DIC was suddenly resolved and bone metastases were well controlled after the chemotherapy combined with anticoagulant therapy and bisphosphonate. The combination of TS-1 and CDDP can be applied for the management of DIC caused by multiple bone metastases.     

A case of gastric cancer with peritoneal recurrence which developed during adjuvant administration of TS-1 showing complete response by weekly docetaxel regimen

A 62-year old man had undergone total gastrectomy for Borrmann type 4 gastric cancer. No peritoneal dissemination was observed at the laparotomy. Pathological examination revealed that the tumor involved the subserosal layer, and that the lymph node metastasis extended to the left gastric nodes. Vascular and lymphatic involvement was also observed. One hundred mg/body of TS-1, an oral 5-fluorouracil (5-FU) anticancer agent, which consisted of tegafur (a prodrug of 5-FU), and two modulators (gimeracil and oteracil potassium) was given from the 16th post-operative day. A course of TS-1 consisted of consecutive administration for 4 weeks followed by 2 weeks rest. The patient complained of abdominal fullness after administration of the second course of TS-1. Computed tomography (CT) revealed massive ascites. The serum carcinoembryonic antigen (CEA) titer was elevated to 13.5 ng/ml. From these findings, the occurrence of peritoneal dissemination was suspected. Weekly docetaxel of 30 mg/m2 (40 mg/body) was given for 3 weeks followed by a week cessation. At the start of the 6th course, the serum CEA was normalized, and CT scan detected the disappearance of ascites without any new lesion. Administration of docetaxel was continued until the 10th course then stopped without relapse of the disease. No dose reduction or postponement of administration were required. The patient has survived without disease one year after cessation of the treatment. Weekly docetaxel is a safe and effective regimen for gastric cancer worth using for a second-line therapy after failure of the 5-FU-based regimen.     

A case of complete response to combination therapy of S-1 and CDDP for Stage IV gastric cancer with Virchow's lymph node and para-aorta lymph node metastasis

The patient was a 53-year-old male with Stage IV gastric cancer with Virchow's lymph node and para-aorta lymph node metastasis. The chemotherapy regimen was given S-1 orally at 80 mg/m(2) day on day 1 to 21 and CDDP intravenously at 60 mg/m(2) day on day 8, repeated for 35 days. After two courses and a reduced regimen with S-1 64 mg/m(2) day plus CDDP 35 mg/m(2) day, the tumor lesion became CR and the serum CEA 575 ng/mL level before therapy decreased to the normal level. The patient received six courses of oral S-1(64 mg/m(2) day)for 28 days followed by a 14- day rest as maintenance therapy. The serum CEA elevated 13 months after the treatment, and the patient received a reduced course and two-course S-1/CDDP therapy. The serum CEA decreased to normal level and the patient has now survived 1 year 5 months without recurrence.     

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.     

Four cases of gastric cancer with multiple hepatic metastases successfully treated with TS-1 in combination with low-dose cisplatinum

We treated five cases for multiple hepatic metastases from gastric cancer with a novel combination of TS-1 and low-dose cisplatinum (CDDP). TS-1 was orally administered at 100 mg/body/day every day or only on weekdays, and 10 mg of CDDP was infused once or twice a week. The efficacy was evaluated by body CT after the treatment. The CT showed more than a 60% reduction of hepatic tumors in four patients. The tumor markers, CEA and CA19-9, were reduced to 10%. The response rate was 80%. Adverse reactions of grade 1 anemia were observed in two patients and grade 1 leucopenia in one patient. The liver function normalized in one patient. The hemoglobin level was increased from 6.8 g/dl to 11.8 g/dl in one patient. In conclusion, this combined chemotherapy of TS-1 and low-dose CDDP proved useful for advanced gastric cancer patients with multiple hepatic metastases, in view of its therapeutic efficacy, patients' quality of life and low toxicity.     

Combination therapy of a novel oral fluorouracil derivative TS-1 with low-dose cisplatin for recurrent and very advanced gastric cancer

The case reports and clinical trials on combination therapy of a novel oral 5-fluorouracil derivative TS-1 with low-dose cisplatin for gastric cancer were reviewed. In the majority of the case reports, TS-1 was administered at 80-120 mg/body per day for 4 weeks followed by a rest of 2 weeks. However, in several case reports, TS-1 administration was slightly shortened such as 3 weeks administration followed by a rest of 2 weeks. The administration of cisplatin (CDDP) varied: every day, weekly, bi-weekly, and so on; the doses were from 1 to 25 mg/m2. CDDP was mostly given at 5-10 mg/body 5 days per week, mimicking the low-dose FP (5-fluorouracil+ CDDP). In most case reports, combination therapies were undertaken on an inpatient basis due to frequent administration of CDDP, while the weekly or bi-weekly CDDP administration regimens were done on an outpatient basis. The case reports demonstrated high efficacies and few adverse effects of the combination therapy. Several case reports showed unresectable cases could be operated curatively after the combination therapy. There have been three phase I clinical trials, two of which were regimens on an outpatient basis. JFMC 27-9902, an inpatient-basis phase I clinical trial, consisted of TS-1 at 80 mg/m2 every day and CDDP at low-dose for 5 days per a week: the regimen consisted of 4 weeks administration and 2 weeks' rest. The recommended dose of CDDP was determined to be 4 mg/m2 in the JFMC27-9902 regimen. In the modified JFMC27-9902 regimen, CDDP was given twice a week on an outpatient basis. This new phase I/II clinical trial has been under way since 2003 December. In conclusion, TS-1 + low-dose CDDP combination therapy will be done on an outpatient basis in future, and may be examined as a neoadjuvant therapy as well as a conventional form of chemotherapy.     

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 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.     

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 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 remnant gastric cancer with multiple bone metastasis and peritoneal dissemination; efficacy of combination therapy of docetaxel and TS-1

A 69-year-old female underwent radical surgery for advanced gastric cancer (Stage IIIA) 7 years ago. She was diagnosed as remnant gastric cancer with multiple bone metastasis and peritoneal dissemination. Treatment with docetaxel and TS-1 was started with the following regimen: daily oral administration of 100 mg/body TS-1 for 14 days, followed by a 7 day rest and infusion of 40 mg/m2 docetaxel on day 1. Two months after the initial administration of docetaxel/TS-1, the sites of the remnant gastric cancer and bone metastasis were reduced in size, and the ALP returned to almost the normal level. The site of peritoneal dissemination had disappeared. Currently (nine months after diagnosis), she is undergoing therapy with TS-1. The combination of docetaxel and TS-1 can be a new tool for the management of gastric cancer with bone metastasis.     

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

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

A case of recurrent advanced gastric cancer with lung metastasis effectively treated by combined chemotherapy of TS-1 and weekly CDDP

We report a case of a patient with recurrent gastric cancer and lung metastasis, who responded remarkably to combination chemotherapy using TS-1 and weekly CDDP. The patient was administered 2 courses of TS-1 (80 mg/m2/day, on day 1-21) and CDDP (25 mg/m2/day, on day 8, 15, 22) every 5 weeks. The regimen was done on an outpatient basis. The treatment resulted in the metastatic tumors in the lung disappearing after 1 course. No severe side effects were observed. This combination therapy proved useful for treating lung metastasis from gastric cancer in this patient.     

A case of advanced gastric cancer with liver metastasis completely responding to CPT-11+low-dose 5-FU+CDDP chemotherapy

The case was a 54-year-old man with type-3 gastric cancer in the cardia accompanied by multiple liver metastasis. He received combination chemotherapy consisting of CPT-11 (60 mg/body, day 1 and 8)+low-dose 5-FU and CDDP (5-FU 500 mg/body/day and CDDP 5 mg/body/day, day 1-5 and 8-12, continuous infusion) every 3 weeks. The initial 2 courses were administered on an inpatient basis,and further courses as an outpatient. After 7 courses of therapy without severe adverse events, not only primary lesion but also hepatic metastasis disappeared. He has been free from disease for 4 months, and chemotherapy was further continued with TS-1 (100 mg/body, day 1-14)+CPT-11 60 mg/body, day 1, 8), every 3 weeks. CPT-11 in combination with low-dose 5-FU+CDDP can be one of the most effective regimens for unresectable advanced gastric cancer.