A case report of bowel obstruction due to peritonitis carcinomatosa using combined administration with CPT-11 and CDDP

We report here a case of recurrent gastric cancer that responded to third-line chemotherapy with CPT-11 and CDDP. The patient was a 61-year-old man with recurrent gastric cancer, who had administered TS-1 for first-line chemotherapy and paclitaxel for second-line chemotherapy. After such therapy, bowel obstruction was revealed due to peritoneal dissemination. The patient underwent third-line chemotherapy with CPT-11 and CDDP after drainage of gastrointestinal juice by nasogastric tube. The treatment schedule for CPT-11 and CDDP therapy consisted of CPT-11 60 mg/m2 div at day 1, day 15 and CDDP 60 mg/m2 div at day 1. It was repeated every 4 weeks. After first administration, the bowel obstruction was improved, so the treatment was continued for 8 months on an outpatient basis. These findings imply that this treatment can be a useful second-line or third-line chemotherapy for unresectable advanced or recurrent gastric cancer.     

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

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

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 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 recurrent gastric cancer with lymph node metastasis successfully treated by CPT-11/CDDP therapy

We report a case ofa 76-year-old man suffering from advanced gastric cancer with lymph node recurrence. Distal gastrectomy was performed for gastric cancer with pylorus stenosis in April 2001. Pathological staging was III A(T3, N1, M0, Cur B). He underwent outpatient treatment with oral administration of UFT 400mg/day as postoperative adjuvant chemotherapy, but stopped after two months because of loss of appetite and general fatigue. Partial liver resection(S4/5)was performed for liver metastasis(S4)in June 2002, and S-1 was administered 80mg/day as adjuvant chemotherapy. However, obstructive jaundice was detected for lymph node recurrence in March 2003, and conducted bile duct stent after PTCD. He started to undergo a biweekly combination chemotherapy of irinotecan (CPT-11)60mg/m / 2 and cisplatin(CDDP)30mg/m2. Three months later, the lymph node had decreased in size. We reduced this therapy, extended the interval, and discontinued it after 24 courses due to adverse reactions, such as leucopenia(grade 3)and general fatigue(grade 2). Afterward, he had no recurrence for over 5 years.     

A case of gastric cancer with peritoneal dissemination who achieved long survival from control of ascites for over 2 years by successive treatments with S-1 in combination with docetaxel as first-line followed by irinotecan in combination with cisplatin as second-line

The patient was a 66-year-old male, admitted and diagnosed as having advanced gastric cancer with peritoneal dissemination, leading to ascites and obstructive jaundice. After reducing the degree of obstructive jaundice, combination chemotherapy of S-1 80mg/m2/day(2 weeks administration and 1 week rest)and docetaxel(TXT)40mg/m2(day 1)was administered from February, 2008. After 3 courses of this regimen, CT revealed no evidence of ascites, and this chemotherapy was successively continued on an outpatient basis until June, 2009. After the relapse of ascites from July, 2009, combination chemotherapy of irinotecan(CPT-11)60mg/m2 and cisplatin(CDDP)30mg/m2 biweekly was performed as second-line chemotherapy, and the ascites disappeared again after around 2 courses of this regimen. This chemotherapy was continued on an outpatient basis until February, 2010. No major adverse reaction to either chemotherapy was observed. This case suggests that these chemotherapies, such as the combination chemotherapy of S-1 plus TXT as a first-line treatment and CPT-11 plus CDDP as the following second-line treatment, can be administered to an outpatient, can keep good patient's QOL and can be one of the effective chemotherapy options for advanced gastric cancer with peritoneal dissemination.     

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.     

A case of stage IV gastric carcinoma with lymph nodes metastases of the paraaorta responding markedly to TS-1

A 64-year-old man had undergone subtotal gastrectomy with a D2 lymphadenectomy for advanced carcinoma of the stomach with paraaortic lymph nodes metastases 12 months earlier. The histopathological findings revealed a well differentiated adenocarcinoma [type 2 macroscopic findings, SE, INF beta, ly2, v1, N2, M1 (LYM)]. On admission, biochemical investigations showed an elevation of CEA, CA19-9, and CA 125. An abdominal ultrasonography and a computed tomography (CT) revealed lymph node swelling of the paraaorta. After non-curative operation, he has received adjuvant chemotherapy with TS-1 plus CDDP. At first, 100 mg/day of TS-1 was orally administered for three weeks followed by two drug-free weeks, with CDDP (60 mg/m2/day) infused on day 8. Next, the treatment course consisted of four-week consecutive administration of TS-1 (80 mg/day) followed by two drug-free weeks, with biweekly infusion of CDDP at a dose of 15 mg/m2. The CT findings revealed that an almost complete reduction of the metastatic paraaortic lymphnodes was obtained after completion of course 1, and was maintained thereafter. No noteworthy adverse reactions were observed and the patient has a good QOL. The patient is now in a good health and continues to undergo low dose TS-1 plus CDDP chemotherapy as an outpatient.     

A case of advanced gastric cancer which has kept partial response with the fifth-line chemotherapy

We report a case of a 48-year-old male with advanced gastric cancer. A total gastrectomy was performed for cancer of remnant stomach. S-1 was administered for cytological cancer cells detected by abdominal cavity lavage as the first-line chemotherapy. After 2 cycles of S-1, cervical lymph nodes were enlarged, and the patient underwent paclitaxel monotherapy as the second-line chemotherapy. After 8 cycles, Virchow lymph nodes were enlarged. The regression of Virchow lymph nodes were observed with a S-1 /CPT-11 combination therapy as the third-line chemotherapy and DOC/CPT-11 as the fourth-line chemotherapy. We then used a combination chemotherapy of CPT-11 60 mg/m2 and CDDP 30 mg/m2 at day 1 and 15, every 4 weeks as the fifth-line chemotherapy. A partial response was achieved after 2 cycles, and has been continued for 7 months. The hematological toxicities and the non-hematological toxicities of grade 2 or higher were not observed. This regimen may be effective for patients with advanced gastric cancer resistant to prior chemotherapy with several agents.     

A case of advanced gastric cancer with obstructive jaundice that responded to TS-1/CPT-11 combination therapy after percutaneous transhepatic cholangio drainage

TS-1/CPT-11 combination therapy was carried out in a case of advanced gastric cancer with liver and lymph node metastases and obstructive jaundice after percutaneous transhepatic cholangio drainage (PTCD). Regression of the primary carcinoma and reduction in size of metastases were observed. Grade 1 fatigue and grade 2 neutropenia were noted as adverse reactions to the treatment. TS-1/CPT-11 combination therapy was useful in this case of advanced gastric cancer with liver and lymph node metastases.     

A case of TS-1 resistant recurrent gastric cancer with lung metastasis responding to TS-1 and irinotecan combination therapy

We report a case of TS-1-resistant recurrent gastric cancer with lung metastasis responding to TS-1 and irinotecan (CPT-11) combination therapy. A 72-year-old man underwent total gastrectomy with pancreaticosplenectomy for advanced gastric cancer on October 18, 2001, and partial hepatectomy for postoperative liver metastasis on August 22, 2002. In March 2004, a chest computed tomography scan revealed metastatic lesions in the bilateral lungs, and he received a single administration of TS-1, resulting in partial response. After 13 courses, this therapy was discontinued due to progressive disease. Then,TS-1 and CPT-11 combination therapy was chosen as the second-line chemotherapy. After 4 courses, a partial response was obtained in lung metastasis, and thereafter has been maintained. He has been treated on an outpatient basis because of no grade 3 or severer adverse reactions. TS-1 and CPT-11 combination therapy could be a promising regimen as the second-line chemotherapy for gastric cancer resistant to TS-1.     

A case of gastric cancer with multiple liver metastasis responding to combination therapy of CPT-11 and CDDP

A 63-year-old man suffering from advanced gastric carcinoma after distal gastric resection had multiple liver metastases 5 months after the operation. He underwent 3 courses of combination chemotherapy of 5-FU 600 mg/day with CDDP 50 mg/day, etoposide 100 mg/day and Leucovorin 30 mg/day for 5 days (FLEP), but progressive disease (PD) was noted. One additional course of combination chemotherapy with CPT-11 140 mg/day and CDDP 40 mg/day biweekly was performed and a complete response (CR) was noted. After 4 months, recurrence of a liver metastasis on S8 was demonstrated and 2 courses of the same chemotherapeutic regimen were carried out. Over 5 months, recurrence of the liver metastasis showed no change (NC) and resection of S8 of the liver was performed. No recurrence was after 6 months, but the patient died 34 months after the first detection of the occurrence of multiple liver metastases. The combination chemotherapy of CPT-11 with CDDP was also administered to other patients at our outpatient clinic and seems to be useful therapy for improving outcome.     

A case of an increase in resectability with preoperative chemotherapy TS-1 combined with CPT-11 for unresectable rectal cancer in downstaging

A 50-year-old woman visited our hospital with a chief complaint of lower abdominal mass. The patient was diagnosed with rectal cancer using colonoscopy and also diagnosed with unresectable rectal cancer because abdominal CT revealed metastases to the liver, lung and lymph node located porta hepatis. The patient was treated with TS-1 combined with CPT-11. The TS-1 (80 mg/m2) was orally administered for 2 weeks and followed by a 2 week interval, and CPT-11 (80 mg/m2) was simultaneously administered biweekly. One cycle of chemotherapy was 28 days. The patient experienced grade 1 leukocytopenia and neutropenia. Abdominal CT revealed partial response after 2 cycles. After 6 cycles, the patient was subjected to curative operation. Pathological efficacy was Grade 1a at lymph node metastasis and Grade 3 at liver metastasis. TS-1 combined with CPT-11 regimen was very feasible and convenient, and obtained a good compliance. So this regimen was promising for unresectable colorectal cancer. In the future, this regimen will be verified in phase III clinical trial and compared with FOLFIRI and FOLFOX regimens.     

A partial response to combined TS-1 and docetaxel chemotherapy enabling a curative resection after the failure of combined TS-1 and CDDP chemotherapy in a patient with unresectable gastric cancer

A 60-year-old man visited our hospital complaining of epigastric pain. Gastrofiberscopy revealed an advanced gastric cancer located on the anterior wall of the antrum. Abdominal computed tomography (CT) revealed metastases to the paraaortic lymph nodes. The patient subsequently underwent combined chemotherapy consisting of TS-1 and low-dose CDDP for the treatment of unresectable gastric cancer. No reductions in the paraaortic lymph node metastases were noted after one cycle. The patient was then treated with TS-1 combined with docetaxel as a second-line chemotherapy. TS-1 (80 mg/m2) was orally administered for 2 weeks followed by a 2 week interval, while docetaxel (25 mg/m2) was simultaneously administered weekly (days 1, 8, and 15). One cycle of chemotherapy was 28 days. An abdominal CT revealed a partial response after 3 cycles. The patient experienced grade 2 leukocytopenia and grade 3 neutropenia. We decided that the patient could undergo a curative resection, and a distal gastrectomy with D2+para-aortic LN dissection was performed. The pathological efficacy was Grade 2. The patient is presently alive with no sign of recurrence after 20 months. Combined TS-1 and docetaxel chemotherapy is a promising second-line regimen for the treatment of unresectable gastric cancer, after treatment with TS 1 combined with CDDP has failed.     

Clinical efficacy of TS-1 combined with cisplatin for advanced cardiac gastric cancer with multiple liver metastases--two case reports

Case 1: A 62-year-old man was introduced to our hospital for Type 1 cardiac gastric cancer. On the abdominal CT, there was evidence of multiple liver metastases. The patient was treated with daily oral administration of TS-1 (120 mg/day) for 3 weeks followed by 2 weeks' rest and infusion of CDDP (60 mg/m2) on day 8 as 1 course. After completion of 1 course, partial response in the primary tumor, and complete responses in the liver and lymph node metastases had been assessed, although the primary tumor increased during the 2 months' rest after 4 courses. Case 2: A 67-year-old man was hospitalized for Type 3 cardiac gastric cancer with multiple liver and lymph node metastases. A combination of TS-1 (100 mg/day), and CDDP (60 mg/m2), and TS-1 (80-50 mg/ day) was used. After 2 courses of TS-1/CDDP and 4 courses of TS-1, the primary tumor decreased significantly in size, and complete responses in the liver and lymph node metastases had been assessed, although the primary tumor, liver and lymph node metastases increased after 6 courses of TS-1. The two cases under study suggest that the combination systemic chemotherapy of TS-1 and CDDP is an effective treatment for advanced gastric cancer with multiple liver metastases in terms of its antitumor effect and QOL of the patients.     

A case of 5-FU-resistant recurrent colon cancer treated with low-dose CPT-11/CDDP on an outpatient basis

We report a case of recurrent colon cancer resistant to 5-FU, whose QOL and PS has been well maintained with low-dose CPT-11/CDDP administered on an outpatient basis for more than 28 months. A 42-year-old male had lymph node recurrence 27 months after curative resection of colon cancer. He had been administered pharmacokinetic modulating chemotherapy (PMC, oral tegafur/uracil plus fluorouracil infusion) after surgery. Combined treatment with CPT-11 (50 mg/m2)/CDDP (6 mg/m2) was performed on an outpatient basis. Nine months of NC was obtained without any severe side effect. Modified administration of this treatment with 5'-DFUR and TS-1 lead to further maintenance of quality of life and performance status. This case suggests the efficacy of low-dose CPT-11/CDDP for cases of 5-FU-resistant colon cancer in terms of QOL and PS.     

A case of TS-1 resistant recurrent gastric cancer responding to TS-1 +CPT-11 combination therapy

A 71-year-old man underwent distal partial gastrectomy for gastric cancer. Four years after surgery, the tumor marker was elevated. Examinations by computed tomography (CT) revealed para-aortic lymphnode swelling and hydronephrosis. The patient treated oral administration of TS-1 (120 mg/day). After 3 courses of treatment of TS-1, progressive disease was observed. TS-1+CPT-11 (TS-1 120 mg/day day 1-14, CPT-11 100 mg/day day 1, 15) combination therapy was then chosen as second-line chemotherapy. After 5 courses of combination therapy, the tumor marker was decreased and para-aortic lymphnodes could not be detected by CT. Only grade 2 leukopenia was observed as an adverse event during the therapy. TS-1+CPT-11 combination therapy could be useful as the second-line chemotherapy for cases of TS-1 resistant recurrent gastric cancer.     

Examination of second-line therapies following administration of low-dose TS-1+CDDP for highly-advanced gastric cancer

Sixteen patients with highly-advanced gastric cancer were administered low-dose TS-1 and CDDP as a first-line treatment, followed by either paclitaxel or CPT-11/CDDP as a second-line treatment. The results of the 2 second-line treatments are reported herein. Overall response rate for the first-line treatment was 55.6%. For the second-line treatments, responses were noted in both the paclitaxel group and the CPT-11/CDDP group. Overall MST was 16.3 months and 1-year survival was 60%. The paclitaxel group, however, showed significantly better prognoses than the CPT-11/CDDP group. Adverse reactions to the first-line treatment were grade 3 leukopenia in 1 patient, with no other reactions over grade 2 observed. No adverse reaction greater than grade 2 was noted during administration of the second-line treatments. These results appear to present ample data that a first-line treatment of low-dose TS-1/CDDP followed by a second-line treatment of paclitaxel at 1/week in the outpatient setting yields improved prognoses and minimal adverse reactions.     

A case of advanced gastric cancer with obstructive jaundice due to multiple liver metastasis successfully treated with the following combination therapy of CPT-11 and cisplatin after combination therapy of paclitaxel and TS-1

A 60-year-old man, who had been admitted to another hospital with complaints of constipation, abdominal fullness and appetite loss, was referred to our hospital for further examination and therapy. The patient was diagnosed as advanced gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice. He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was orally administered for 2 weeks followed by one drug-free week), and showed a remarkable response. However, because of ascites, elevated serum CEA level and resistance in the liver metastasis and gastric region, we attempted two courses of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT-11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1 followed by two drug-free weeks) which showed a remarkable response. Two courses of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT-11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed by two drug-free weeks) on an outpatient basis. However, the patient showed resistance to the latter combination therapy, increased ascites due to suspicious peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the liver. He died on May 23, 2006, about ten months after initial diagnosis. We reported a case of successful treatment of combination chemotherapy for advanced gastric cancer with obstructive jaundice due to progressive multiple metastatic tumors in the liver and obtained comparative long-term survival maintaining high quality of life.     

A case of gastric adenosquamous carcinoma with abdominal paraaortic lymph node metastases successfully treated by TS-1 plus CDDP neoadjuvant chemotherapy

A 62-year-old woman was admitted for anemia. An endoscopic examination revealed type 2 cancer from the upper body of the stomach to the antrum, and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative diagnosis was cStage IV gastric cancer (cT 3, cN 3, cH 0, cP 0, cM 0). Since a curative operation was deemed impossible, we conducted neoadjuvant chemotherapy using TS-1 plus cisplatin (CDDP) for downstaging. TS-1( 100 mg/day) was orally administered for 3 weeks,and CDDP (60 mg/m2) was given intravenously on day 8. Appetite loss of grade 3 and erythropenia of grade 1 were observed. After two courses of chemotherapy the primary lesion and the paraaortic lymph nodes were significantly reduced in size. She was judged as clinical PR, followed by distal gastrectomy and lymph node dissection, resulting in curability A. Histopathologically, the tumor was diagnosed as adenosquamous carcinoma of the stomach with lymph node metastasis at only No.3. This case suggests that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric adenosquamous carcinoma with massive lymph node metastases.