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 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 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 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.     

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 metastatic colon carcinoma in which a continuous intrahepatic artery-infusion of 5-FU leucovorin and cisplatin, and systemic chemotherapy with CPT-11 was very effective

We report a patient with metastatic colon carcinoma who was treated effectively with a continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and systemic chemotherapy with CPT-11. A 50-year-old man was diagnosed as having well differentiated adenocarcinoma of the sigmoid colon with multiple liver metastases in March, 1997. Left hemicolectomy and subsequent catheterization into the common hepatic artery via the gastroduodenal artery were performed in April, 1997. He was treated with 3 courses of continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and two courses of systemic chemotherapy with CPT-11 during hospitalization, followed by 6 courses of a similar intraarterial therapy in an outpatient setting. Reinstallation of the catheter into the hepatic artery via the femoral artery was performed because of occlusion of the reservoir. During the 6th course of intraarterial therapy, diarrhea, nausea, and vomiting appeared and angiography revealed a narrowing of the hepatic artery. Therefore, the intrahepatic artery-infusion therapy was reinitiated with doses of 5-FU, Leucovorin and cisplatin reduced to approximately 80%. After 5 courses of this therapy, the computed tomography scan showed a marked decrease in the size of the metastatic hepatic lesions by 90%, and the serum level of CEA decreased from 657.7 ng/ml to 4.5 ng/ml. No severe side effects were seen during the treatment. Though multiple lung metastases were indicated during the intrahepatic artery-infusion therapy, both the liver and lung metastases have been well controlled with continuous intrahepatic artery-infusion chemotherapy and systemic chemotherapy. The continuous intrahepatic arterial infusion of 5-FU, leucovorin and cisplatin appears to be very effective for the treatment of colon carcinoma with liver metastasis without reducing the quality of life.     

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.     

Huge unresectable multiple hepatic metastases of rectum cancer responding to combined therapy with FOLFIRI +bevacizumab - a case report

We report a patient with a huge multiple hepatic metastases of rectal cancer treated by combination of infusional 5-FU, Leucovorin, irinotecan(FOLFIRI), and bevacizumab(BV). The patient was a 60-year-old man with cancer of the rectum, with huge multiple hepatic metastases. The serum carcinoembryonic antigen(CEA)level was 3,979.6 ng/mL, and the carbohy- drate antigen(CA)19-9 level was 66,562.6 U/mL. The patient received combined chemotherapy with FOLFIRI and BV. After completion of 8 courses, abdominal CT scans revealed that those low-density areas of the liver had reduced. The patient was judged to have achieved PR. He received combined therapy for 42 courses, and his response is SD at this point. No grade 2 adverse event occurred throughout chemotherapy. This case suggests that combined therapy with FOLFIRI+BV may be an effective regimen for advanced rectal cancer with huge multiple hepatic metastases.     

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 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.     

Resection of pancreatic cancer and simultaneous lung metastasis--a case report of successful in tumor dormancy mainly by postoperative 5-fluorouracil-based chemotherapy

A 48-year-old male patient was admitted to our institution with left hypochondralgia. Preoperative serum CEA was 504 ng/ml. Under a radiological diagnosis of simultaneous double cancer of the pancreas and lung, resection was performed. Pathological study revealed primary pancreatic cancer with lung metastasis. After the operation, serum CEA fell to 55 ng/ml. Seventeen months later, bowel obstruction occurred and serum CEA was 140 ng/ml. One course of systemic chemotherapy, using the combination of CDDP, 5-FU and Leucovorin, was successful. After another three months, however, the same clinical symptoms occurred. With no response to the prior chemotherapy regimen, surgery was undertaken and a mass at the mesentery was removed. Fifty-nine months have passed since the initial operation and the patient is free of disease, though his serum CEA is around 50 ng/ml. In conclusion, there are cases of pancreatic cancer in which tumor dormancy can be achieved by postoperative 5-FU based chemotherapy.     

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

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

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

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

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 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 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 of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.     

Three successful case reports of advanced gastric cancer with chemotherapy

We report three successful cases with continuous systemic chemotherapy for advanced gastric cancer. Case 1: A 67-year-old male with gastric cancer. Abdominal CT showed the invasion in the pancreas and as a result, continuous systemic infusion of low-dose cisplatin (CDDP 20 mg/day) and 5-fluorouracil (5-FU 1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 25 days. Three months after the chemotherapy, the main tumor was remarkably reduced (downstaging was obtained), and consequently, total gastrectomy was performed. Case 2: A 78-year-old male with gastric cancer and hepatic multiple metastases. Abdominal CT scan before operation did not reveal the hepatic metastasis. In the operation for distal gastrectomy, we found multiple metastases on the surface of the liver. Continuous systemic infusion of low-dose CDDP (20 mg/day) and 5-FU (1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 2 days. One month after the chemotherapy, Liver metastases had almost disappeared. Case 3: A 73-year-old male had received a distal gastrectomy based on the diagnosis of gastric cancer. The tumor marker, CA19-9, immediately decreased after the operation, but had increased again. He was treated with a combination chemotherapy of TS-1 and CDDP. The treatment consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. CDDP of 10 mg/day was infused intravenously (day 1-5). Four weeks after the infusion, CA19-9 had returned to almost normal. We conclude that the combination chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for advanced and metastatic gastric cancer.