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.     

Complete response to treatment with low-dose FP therapy in a patient with stage IVB primary hepatocellular carcinoma with multiple lung and bone metastases

We report a case in which low-dose FP (5-fluorouracil/cisplatin, 5-FU/CDDP) therapy was remarkably effective for stage IVB advanced hepatocellular carcinoma (HCC) with lung and bone metastases. 5-FU of 250 mg/body/day was continuously infused over 24 hours and CDDP of 10 mg/body/day was infused over 30 minutes from day 1 to day 5 in a week. Administration was continued for 4 weeks as 1 cycle. An 81-year-old woman was diagnosed with HCC in S3 and underwent a transcatheter hepatic arterial embolization (TAE) for the tumor in December 2000. The patient complained of lumbago and hip pain in July 2001 and was admitted for dysbasia in September 2001. On admission, the level of serum AFP and PIVKA-II elevated to a remarkable 59,300 ng/ml and 25,700 AU/ml. Chest computed tomography (CT) showed multiple bilateral lung metastases and abdominal CT showed a tumor 12 x 11 x 10 cm in diameter in the right, iliac bone. No recurrent sign was found in the liver except for the accumulation of Lipiodol. Low-dose FP therapy of 2 cycles was performed. The levels of serum AFP and PIVKA-II decreased to 374 ng/ml from 59,300 and to 35 AU/ml from 25,700, respectively, after this therapy. The CT findings revealed that a complete response (CR) was obtained for lung metastases and a partial response (PR) was obtained for bone metastases after completion of course 2, and maintained thereafter. The oral UFT of 600 mg was administered after completion of course 2 in the outpatient setting. The level of AFP and PIVKA-II decreased to 13.2 ng/ml and to 26 AU/ml, respectively, in February 2002. No sign of recurrence was seen during the 13 months of follow-up after low-dose FP therapy. Toxic events consisted of only leukopenia (grade 1). Her quality of life (QOL) was fair during this therapy. Low-dose FP therapy is possibly useful for patients with stage IVB advanced HCC.     

A case of advanced hepatocellular carcinoma with portal invasion resected after treatment by continuous intra-arterial chemotherapy with cisplatin and 5-fluorouracil

A 67-year-old male diagnosed as having inoperable advanced hepatocellular carcinoma with portal invasion was able to undergo resection after continuous intra-arterial chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP). These were continuously administered for 24 hours at doses of 5-FU of 250 mg and CDDP of 5 mg/day, from day 1 to day 5 in a week, repeated 6 times. In additions to the reductions of the levels of AFP and PIVKA-II from 212.6 ng/ml and 16,100 mAU/ml to 11.8 ng/ml and 12 mAU/ml, respectively, the volume of the tumor and the portal invasion were diminished remarkably. As a result, a left extended hepatectomy could be performed. No sign of recurrence was seen during 16 months of follow-up after the operation. Given the above results, continuous intra-arterial chemotherapy with 5-FU and CDDP therapy may be effective for patients with hepatocellular carcinoma.     

A case of hepatocellular carcinoma responding to hepatic arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil]

A 74-year-old man had multiple liver recurrence of hepatocellular carcinoma (HCC) after extended left hepatectomy. He was treated by continuous hepatic arterial infusion (HAI) chemotherapy with low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) via an implanted reservoir. A catheter was inserted percutaneously into the hepatic artery using the Seldinger technique. The patient was administered 10 mg of CDDP on day 1 and 500 mg/day of 5-FU for 4 days as one course. Four courses were administered and the PIVKA-II level decreased from 427 to 216 mAU/ml. However, infusion port problems led to interruption of chemotherapy and PIVKA-II increased to 798 mAU/ml. His chemotherapy was changed to 10 mg of CDDP on day 1 and 750 mg/day of 5-FU for 2 days. After five courses were administered, PIVKA-II decreased to 540 mAU/ml. This patient is still alive 15 months after the start of therapy. This case suggests that HAI with low-dose CDDP and 5-FU might be useful for prolonging the survival of HCC patients with a good quality of life.     

A case of Vp4 hepatocellular carcinoma treated with surgical resection and continuous intrahepatic artery infusion chemotherapy of low-dose cisplatin and 5-fluorouracil

A 49-year-old woman was admitted to our hospital because of hepatocellular carcinoma (HCC). She had no hepatitis virus. Serum AFP and PIVKA-II levels were as high as AFP 329.4 ng/ml (AFP-L3% 73.1%) and 281 AU, respectively. Portal venous thrombus was observed from the right portal branch to left portal branch and superior mesenteric vein. An extended right hemihepatectomy with extraction of portal venous thrombus was performed. On postoperative day 8, low-dose cisplatin (10 mg/day for 5 days/week) and 5-fluorouracil (250 mg/day for 5 days/week) were administered through the hepatic artery for 4 weeks. After chemotherapy, one intrahepatic metastasis appeared and RFA was performed for this tumor. At 16 months after surgery, she had multiple lymph node metastases and died at 20 months after the surgery without intrahepatic metastasis. Low-dose CDDP/5-FU intra-hepatic artery infusion chemotherapy was effective for prevention of intrahepatic recurrence after resection of HCC with portal venous thrombus.     

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 synchronous gastric and hepatocellular carcinoma successfully treated by TS-1 and hepatic arterial infusion chemotherapy (HAI) of low-dose CDDP

A 75-year-old man underwent distal gastrectomy for advanced gastric cancer with liver and lymph node metastases and synchronous hepatocellular carcinoma in April 2004. HAI with low-dose CDDP/TS-1 combination therapy was initiated after gastrectomy. Liver and lymph node metastases decreased significantly, with achievement of a partial response (PR) and a complete response (CR), respectively, and the hepatocellular carcinoma was reduced to 54.1% of its initial size after 3 sessions of this chemotherapy. These results suggested that combined chemotherapy with TS-1 and HAI with low-dose CDDP was not only useful for liver and lymph node metastases from gastric cancer, but for hepatocellular carcinoma as well.     

A case of advanced hepatocellular carcinoma with lung and bone metastases effectively treated by orally administered UFT

A 52-year-old male underwent hepatic subsegmentectomy for hepatocellular carcinoma (HCC). Five months later, a recurrent tumor was found in the liver and transcatheter arterial embolization (TAE) was performed. However, recurrent tumors were growing rapidly with multiple lung and bone metastases. The titer of serum AFP was elevated to 896,095 ng/ml and the titer of serum PIVKA-II was elevated to 1294.5 AU/ml. The patient was treated by oral administration of UFT (600 mg/day). Two weeks later, his general condition was improved, and several months later, the liver tumor, multiple lung metastases and multiple bone metastases had almost disappeared. The titers of serum AFP and PIVKA-II were reduced to the normal range. He has maintained a good state of health for about four years now. This case suggests the clinical usefulness of UFT for advanced HCC.     

Successful treatment for advanced hepatocellular carcinoma by hepatic arterial infusion of CDDP powder as second-line chemotherapy

A 72-year-old man with type C liver cirrhosis had suffered from hepatocellular carcinoma (HCC) since April, 2001. HCC spread diffusely all over the right lobe of his liver, and the serum alpha-fetoprotein (AFP) value increased up to 42,696 ng/ml in June of 2004. He was implanted with a port-catheter system, and hepatic arterial infusion chemotherapy (HAIC) using low-dose of CDDP and 5-FU was started. However, it was not effective and after 4 months, the serum AFP level increased up to 755,030 ng/ml, ascites appeared, and gastro-esophageal varices also spread. No definite metastasis was detected, then we started to second-line chemotherapy. He was then given HAIC using CDDP powder for intraarterial use (CDDP 50 mg/m(2)/20 min, monthly). After 3 courses, the serum AFP level decreased to 9 10 ng/ml, and abdominal CT revealed that the main tumor had regressed and ascites had disappeared. After one more course, the serum AFP value decreased to 8 ng/ml and complete response was achieved on abdominal CT imaging. There was no major complication related to the chemotherapy. HAIC for advanced HCC using LFP has been reported to achieve favorable results, but no other regimens have been proved to the standard for HCC. HAIC using CDDP powder for advanced HCC may be beneficial as the second-line chemotherapy.     

Clinical application of protein induced by vitamin K antagonist-II as a biomarker in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II) is an effective serum biomarker for HCC diagnosis and prognosis. Combined with another serum biomarker α-fetoprotein (AFP), the sensitivity and specificity of HCC diagnosis can be improved to a maximum of 94 and 98.5 %, respectively. PIVKA-II alone or in combination with AFP and/or AFP-L3 was effective in predicting the treatment response and clinical outcome of curative hepatic resection, chemotherapy, targeted therapy, radiotherapy, and liver transplantation. Japanese clinical guidelines recommend the combined use of PIVKA-II and AFP for the diagnosis of HCC, management of high-risk population, and prognosis of anticancer treatment. Further, PIVKA-II as a functional target promoted HCC cell proliferation, invasion, and metastasis by activating c-Met and other signal transduction pathways. Inhibition of PIVKA-II may provide a selective and effective therapy for HCC.     

Evaluation of des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma

We measured des-gamma-carboxyglutamic acid prothrombin (protein induced by vitamin K absence or antagonist-Factor II: [PIVKA-II]) in plasmas of normal subjects, patients with thrombotic disease, those with hepatic disease including hepatocellular carcinoma, and those with carcinoma of other tissues, and compared the results with results of blood coagulation tests used for the examination of hepatic function. In addition, in the patients with hepatic disease, PIVKA-II and alpha-fetoprotein (AFP) levels were compared. The PIVKA-II level was frequently high in patients with thrombotic disease given warfarin therapy and those with hepatocellular carcinoma. However, in patients with thrombotic disease who were not given warfarin therapy, no significant correlation was seen between the PIVKA-II value and the results of the thrombotest or hepaplastin test, suggesting no association between the PIVKA-II level and the degree of impairment of hepatic function. In 70 patients with hepatocellular carcinoma, the percentage of patients positive for PIVKA-II (greater than or equal to 0.1 micrograms/ml) and those positive for AFP (greater than or equal to 20 ng/ml) were similar (77% and 74%, respectively). Pearson's correlation of coefficient between the PIVKA-II value and the AFP value in the 70 patients was 0.463. However, false-positive rates in patients with hepatic disease other than hepatocellular carcinoma were lower for PIVKA-II. Combined assessment of PIVKA-II and AFP increased positive rates and allowed exclusion of false-positive patients. The plasma PIVKA-II level is suggested to be useful as an indicator of warfarin control in patients with thrombotic disease, as a marker of hepatocellular carcinoma, and is particularly of value when assessed in combination with AFP.     

A case of complete response in a primary lesion treated by combined chemotherapy of TS-1 and CDDP for small cell carcinoma of the stomach with liver metastasis

A 75-year-old male patient with small cell carcinoma of the stomach and liver metastasis was treated by combined chemotherapy of TS-1 and CDDP. One course consisted of TS-1 (120 mg/day) administered for 14 days followed by 14 days rest. CDDP (108 mg/day) was administered by 24-hour continuous intravenous infusion at day 8 after the start of TS-1. After 3 courses, endoscopic examination revealed complete disappearance of the primary tumor with no cancer cells detected by endoscopic biopsy. CT-scan showed that the metastasis of the left lobe of the liver had disappeared and also that the metastasis of the right lobe of the liver was remarkably reduced (75%). The primary lesion was estimated CR, the metastasis PR, and the synthesis PR. The TS-1/CDDP chemotherapy regimen is considered effective for small cell carcinoma of the stomach with liver metastasis.     

An advanced pulmonary adenocarcinoma case in which TS-1 proved effective

A sixty-two-year-old female presented with non-small-cell lung carcinoma with multiple bone metastasis. Combination chemotherapy with CBDCA and GEM was implemented, but as no effect was obtained, TS-1 was begun with a single course of oral administration of 100 mg/day continuously for 28 days followed by a 14-day rest. Following the start of TS-1, PR of the primary tumor was obtained, and whole-body bone scintigraphy revealed a reduction in abnormal areas of uptake. The woman continues to receive TS-1 orally as an outpatient.     

A case of hepatocellular carcinoma with bone metastasis which responded to oral administration of UFT

A 61-year-old male was referred to our hospital for evaluation of right upper arm pain. He was diagnosed as having primary hepatocellular carcinoma with bone metastasis by his high titer (111,683 ng/ml) of serum alpha-fetoprotein, computed tomography and abdominal angiography, and so UFT therapy, 400 mg daily, was instituted. After 2 months of this therapy, the titer of serum alpha-fetoprotein gradually decreased. Seven months later, the titer was 3,997 ng/ml and reduction of the hepatic tumor size was shown by computed tomography and ultrasonography. Furthermore, the right upper arm pain diminished and X-ray examination revealed remarkable improvement. During chemotherapy, there was no severe side effect apart from mild anemia and the patient is presently still alive. This case suggests the efficacy of UFT for the treatment of primary hepatocellular carcinoma.     

A case of giant hepatocellular carcinoma treatable with radio frequent ablation therapy after effective UFT administration

A 71-year-old man was diagnosed with giant hepatocellular carcinoma (HCC) and hepatitis C cirrhosis at a nearby hospital. Image diagnosis showed no other metastasis, but the tumor was very huge with daughter nodules in the bilateral lobe of the liver. He was thus treated by oral administration of UFT (300 mg/day). Two months later, the giant liver tumor had shrunk remarkably, and the daughter tumors had disappeared. Eight months later, the levels of serum AFP and PIVKA-II had also reduced remarkably. Twelve months following the first treatment, the levels of both serum AFP and PIVKA-II began increasing again, and he was referred to our hospital. CT showed 2 liver tumors, 1 of which showed viability with moderately differentiated hepatocellular carcinoma and the other evidencing necrosis histologically. Radio frequency ablation therapy was performed for 2 tumors by open laparotomy. It was considered that administration of UFT is a useful and safe therapy for far advanced HCC.     

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 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.     

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 advanced gastric carcinoma successfully treated with TS-1/CDDP as a neoadjuvant chemotherapy

We report a patient with gastric carcinoma successfully treated with TS-1/CDDP as a neoadjuvant chemotherapy. The patient was a 72-year-old man who had suffered from general malaise with severe anemia and was diagnosed as type 2 carcinoma, having bulky N2, with suspected invasion of the pancreas. TS-1 (100 mg/day) was administered orally every day for 21 days followed by 14 days rest, and CDDP (20 mg/body) was administered by intravenous infusion at day 8, as one course. He was treated as an outpatient, and two courses of treatment resulted in a marked reduction of the lymphnode metastasis without toxicity. Subsequently, he underwent curative surgery consisting of total gastrectomy with D2 lymph node dissection. TS-1/CDDP therapy is very useful as a neoadjuvant chemotherapy especially for an outpatient until surgery.     

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.