A case of unresectable gastric cancer successfully treated with combination chemotherapy of S-1 + CPT-11

A 70-year-old female, with type III gastric cancer underwent a staging laparoscopy in September 2004. Judging from the results of endoscopy, enhanced CT and staging laparoscopy, we finally diagnosed the patient with stage IV (T3N2MOHOP1CY1), and we started a combination chemotherapy of S-1 + CPT-11 (S-1: 80 mg/m2, day 1-21/35 days, CPT-11: 80 mg/m2, day 1, 15/35 days) from October 2005 to January 2007. Enhanced CT after 2 courses of the combination chemotherapy showed partial response (PR) in the primary lesion. PR continued up to the 13 courses. The CT and gastro fiberscope finally showed complete response (CR) with Group I in biopsy. During these procedures, the grade 3 of neutropenia, grade 1 of diarrhea and grade 1 of fatigue occurred as adverse events. In January 2007, Virchow and, abdominal lymph node metastases were detected, and that we judged the metastases as progressive disease (PD). Nevertheless, the second-line of paclitaxel chemotherapy (70 mg/m2, days 1, 8,15/28 days) has started and she was being judged PD after 2 courses, she died in April 2007.     

A case of advanced pancreatic cancer successfully treated by combined chemotherapy of S-1 and gemcitabine

The patient was a 71-year-old woman. In March of 2007, she experienced abdominal pain, and consulted a physician at our hospital. She was followed on a outpatient basis, but the symptom did not improve, so she consulted our division. As a result of examinations, pancreatic head tumor, multiple liver metastasis, and para-aortic lymph node swelling were detected. She was then admitted for chemotherapy in our hospital. She was treated with combined chemotherapy of S-1 and GEM. Tumor marker(CEA, CA19-9)decreased and the size of the pancreatic head tumor and liver metastasis decreased. No toxic events were observed due to this therapy. She was treated as an outpatient, and was considered to have good quality of life.     

A case of advanced pancreatic cancer successfully treated by combined chemotherapy of S-1 and gemcitabine as second-line chemotherapy

The patient was a 63-year-old man who suffered from advanced pancreatic cancer (T 4 N 3 M 0, Stage IVb). Palliative operation was performed for obstructive jaundice. He was treated with chemotherapy of gemcitabine (GEM) alone as first-line, and combined chemotherapy of GEM and S-1 as second-line. Both therapies were effective for this patient. Tumor marker (CA 19-9) decreased after chemotherapies (first-line: 5,692 U/mL to 70 U/mL, second-line: 4,877 U/mL to 562 U/mL). No toxic events were observed due to these therapies, so he was treated as an outpatient for about 2 years. It was considered that he had a good quality of life.     

A case of gastric cancer with peritoneal dissemination successfully treated by S-1/paclitaxel combination chemotherapy

A 62-year-old woman visited our hospital with diarrhea, bloating, vomiting, and black stool. Borrmann-type 3 gastric cancer with hemorrhaging was revealed by stomach endoscopy. The biopsy showed a poorly-differentiated adenocarcinoma. Moreover, peritoneal dissemination was found by computed tomography and we combined S-1 80 mg/m2(4 weeks administration and week rest)with paclitaxel(PTX)50 mg/ m2 (day 1, 8, 15, 3 weeks rest). After 2 courses, endoscopy showed tumor shrinkage. Therefore, we conducted total gastrectomy with resection of gall bladder and spleen. The final findings were Stage II .We conducted S-1/PTX combination chemotherapy(4 courses)followed by monotherapy as adjuvant chemotherapy. Recently, the woman had been living without relapse four years after operation.     

A case of gastric carcinoma with peritoneal metastasis successfully treated by combination chemotherapy of S-1 and cisplatin

This case is a 69-year-old woman. We diagnosed gastric cancer and cholecystolithiasis by close inspection of abdominal pain. Because preoperative diagnosis was T2N0M0, Stage I B, we performed an operation. Many lesser tubercles were shown, and were diagnosed as peritoneal metastases pathologically. The tumor in corpus ventriculi infiltrated out of gastric serosa. We judged that curative resection was impossible and finished the operation after giving an intra-abdominal dosage of cisplatin(CDDP)at 85mg. After operation, 3 courses of performed S-1/CDDP combination chemotherapy were performed. Because we observed contraction of the main lesion and could not point out the peritoneal metastases and ascitis, we performed a second look operation. All the nodules found with peritoneal and rectouterine excavation had disappeared and we performed distal gastrectomy. The postoperative diagnosis was pT2(MP), pN0CY0, Stage I B, Cur A, therapy grade 1a. Chemotherapy does succeed, and this is a valuable case in which a radical operation could be performed.     

Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer

Purpose

The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic cancer.

Methods

Patients were randomly assigned to receive GS (oral S-1 60 mg/m² daily on days 1–15 every 3 weeks and gemcitabine 1,000 mg/m² on days 8 and 15) or gemcitabine (1,000 mg/m² on days 1, 8, and 15 every 4 weeks). The primary endpoint was progression-free survival (PFS).

Results

One hundred and one patients were randomly assigned. PFS was significantly longer in the GS arm with an estimated hazard ratio (HR) of 0.65 (95 % CI 0.43–0.98; P = 0.039; median 5.3 vs 3.8 months). Objective response rate (ORR) was also better in the GS arm (21.6 vs 6 %, P = 0.048). Median survival was 8.6 months for GS and 8.6 months for GEM (HR 0.93; 95 % CI 0.61–1.41; P = 0.714). Grade 3–4 neutropenia (44 vs 19.6 %, P = 0.011) and thrombocytopenia (26 vs 8.7 %, P = 0.051) were more frequent in the GS arm.

Conclusions

GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer.     

A case of multiple liver metastases of gastric cancer successfully treated by combination chemotherapy of S-1 and paclitaxel

A 54-year-old man underwent distal gastrectomy for early gastric cancer in September 2002. CT performed 6 months after the operation revealed liver metastases, and they were resected. Hepatic arterial infusion therapy of 5-FU was performed; however, multiple liver metastases appeared in October 2003. We added arterial infusion of CDDP to 5-FU, but liver metastases increased. We then applied a combination chemotherapy of S-1 and paclitaxel from February 2004. Subsequently, stable disease continued, and after 67 courses of S-1 plus paclitaxel, we changed the administration to S-1 alone from August 2009. After that, liver metastases did not increase, so we discontinued chemotherapy on August 2010, followed by observation. Progression of liver metastases has not been to date.     

A case of advanced mullerian cancer successfully treated with S-1 chemotherapy

A 79-year-old woman was referred to our hospital with complaints of dyspnea. She was diagnosed with massive pleural effusion and cytology demonstrated the presence of adenocarcinoma, but no solid tumors were found in the systemic examination. Her serum CYFRA and CA125 level were increased. She was diagnosed with an effusion type of lung cancer or a cancer of unknown origin. S-1/CDDP was the chemotherapy of choice. After 2 courses of the treatment, her serum CYFRA level and CA125 level were normalized, and a chest CT detected no pleural effusion. Two years and 3 months after the first treatment, her CA125 level was increased. We found an FDG accumulation in her pelvic lesion by PET examination. To identify the FDG accumulated lesion in her pelvis, an operation was performed. Histopathological examination of the right ovary demonstrated the presence of an adenocarcinoma. Postoperatively, we administered 2 courses of paclitaxel/carboplatin combination treatment, considering the right ovarian tumor was the primary lesion. The patient remained alive and in good condition without any signs of recurrence 2 years after second treatment. This case suggests that S-1 therapy may be effective for patients with mullerian cancer.     

A case of intrahepatic cholangiocarcinoma successfully treated by hepatic arterial infusion chemotherapy

The patient was a 67-year-old man who had been operated for eshophageal cancer 4 years ago. He was diagnosed as intrahepatic cholangiocarcinoma by CT after 2 years of the operation. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, levofolinate calcium (L-LV) and 5-FU with chronomodulation. After a few more months of the treatment, abdominal CT revealed that the size of hepatic tumor decreased remarkably. There were no side effects without bone marrow suppression (grade 1). It seemed that hepatic arterial infusion chemotherapy with chronomodulation may be an effective strategy against intrahepatic cholangiocarcinoma in high risk case.     

A case of elderly advanced squamous cell lung carcinoma successfully treated with nedaplatin and S-1 combination chemotherapy

A 7 4-year-old male was referred to our hospital for an abnormal chest shadow pointed out by a medical examination. A chest computed tomography revealed a tumor shadow 39 X 32mm in size in his left upper lobe in January, 2010. Pathological examination of biopsy specimens showed squamous cell carcinoma of the lung. Although there was no distant metastasis, multiple metastases to mediastinal lymph nodes was noted. He was diagnosed as Stage III A(cT2aN2M0). Considering his age and the histology of the disease, systemic chemotherapy with nedaplatin and S-1 was performed. The diameter of the primary lesion was decreased from 39mm to 18mm after 4 courses of chemotherapy, and was considered as partial response (PR)according to the RECIST criteria. The adverse events were grade 2 appetite loss, grade 3 neutropenia, and grade 2 thrombocytopenia. Recently, various new agents for treating non-squamous cell lung carcinoma have been developed, but there has been little progress in the treatment of squamous cell lung carcinoma. We experienced a patient with advanced squamous cell lung carcinoma who responded with CDGP/S-1 combination chemotherapy. We are now conducting a phase I / II clinical study to verify the usefulness of this regimen against advanced squamous cell lung carcinoma.     

A case of unresectable advanced gastric cancer treated with S-1/low-dose CDDP combination chemotherapy through jejunostomy

A 70-year-old woman with unresectable advanced gastric cancer accompanied by peritoneal dissemination underwent jejunostomy, and was treated with S-1 and low-dose CDDP. One course consisted of S-1 (80 mg/day) via an intestinal fistula tube from days 1 to 14. This was followed by 7 days rest, and CDDP (20 mg/day) was administered by 1-hour continuous intravenous infusion on day 1 and 8. She continued to receive this chemotherapy for a total of 14 courses, followed by 3 courses of a weekly paclitaxel regimen. She died 14 months after surgery. All chemotherapy had been conducted in an outpatient setting. We concluded that the administration of S-1, combined with low-dose CDDP (div) through a jejunostomy, can improve the quality of life (QOL) of a patient who has unresectable advanced gastric and is incapable of oral intake. We report this rare case with a review of the literature.     

A case of repeated bone metastases of breast carcinoma successfully treated by S-1 chemotherapy

We report a case of breast carcinoma with repeated recurrences in the right bone. The recurrent site of the bone was treated by radiation therapy with a total of 3 7. 5 Gy irradiation, and chemotherapy with the CMF regimen. After 2 years, recurrence was suspected in the same region because there was an elevation of the NCC-ST-439 tumor marker. We carried out chemotherapy with S-1 100mg/body/day. The NCC-ST-439 value returned to within the normal range after 3 months' administration of S -1, and continued in the normal value for 20 months.     

A long-term survival case of unresectable intrahepatic cholangiocarcinoma treated with chemotherapy

An 83-year-old man commuting to our hospital with postoperative ascending colon cancer was pointed out an increase of CA19-9. CT scan revealed an intrahepatic cholangiocarcinoma in the left lobe. In May 2007, an operation was performed. We recognized a lymph node swelling in the hepatoduodenal ligament. Pathologically, it was moderately differentiated adenocarcinoma. Therefore, the operation did only the cholecystectomy. Gemcitabine was administered once a week for 3 weeks followed by a week rest. It was administered for about 20 months and the evaluation during the period was PR or SD. Afterwards, the tumor had increased gradually. Gemcitabine was changed to S-1. Then, S-1 was changed to gemcitabine again because the enlargement of the tumor and the rise of tumor markers were observed. Consequently, tumor markers decreased. Now, the patient is under an outpatient care maintaining ADL.     

A case of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel

A 70-year-old man with gastric cancer of Borrmann type 3, liver metastases and peritoneal dissemination was treated by combination therapy of S-1 and docetaxel (DOC). He received DOC intravenously at 40 mg/m(2) on day 1 and S-1 orally at 100 mg/body on day 1 to 14, repeated every 28 days. After 2 courses of treatment, a CT scan revealed improvement of the gastric wall thickness, the eminent decrease of the peritoneal fluid and the reduction of the liver metastasis. After 3 courses of treatment, the primary lesion was remarkably improved on endoscopic examination, and the tumor marker normalized after 4 courses of treatment. Toxicities included leukocytopenia (WHO grade 3), neutropenia ( grade 3), anorexia (grade 2), and nausea (grade 2). Outpatient chemotherapy was possible by reduction of dose (S-1 100--> 80 mg/body, DOC 40--> 32 mg/m2). The response was maintained on CT and endoscopic examination after 21 courses of treatment. A case of an advanced gastric cancer patient successfully treated by combination therapy of S-1 and DOC was reported.     

A case of unresectable advanced pancreatic tail cancer successfully treated with gemcitabine hydrochloride

We report a case of a 76-year-old female with unresectable advanced pancreatic tail cancer in whom systemic chemotherapy using gemcitabine hydrochloride was effective. The patient came to our hospital with a complaint of upper abdominal discomfort and was diagnosed as an advanced pancreatic tail cancer with severe vessel invasion. A curative operation was thought to be impossible, so gemcitabine hydrochloride was administered (800 mg/m2/week x 3/4 weeks). After 2 courses, the CEA, CA19-9 and SPan-1 value were decreased, and reduced tumor size was identified. Sixteen months after the first diagnosis, she died dissemination.     

A multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer

Purpose

To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer.

Methods

Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m² was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m² was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point.

Results

A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1–22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17–48%]. The median response duration was 6.0 months (95% CI 4.6–8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9–8.0 months), and the median overall survival was 8.4 months (95% CI 5.7–11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%).

Conclusions

Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.     

A case of pancreatic acinar cell carcinoma with a giant liver metastasis successfully treated with combination of gemcitabine and peroral S-1

Pancreatic acinar cell carcinoma is rare, and its incidence is less than 1% of all the malignant pancreatic tumors. Little is reported on effectiveness of chemotherapy. We report a 64-year-old male patient with pancreatic acinar cell carcinoma and a giant metastatic liver tumor, which responded to combination chemotherapy with gemcitabine(GEM)and peroral S-1 administration. The patient had upper abdominal pain and hypervascular tumors in liver(15 cm in diameter)and pancreas tail (3 cm in diameter), which were detected by an enhanced abdominal computed tomography(CT)scan, and was admitted for further examination. Abdominal angiography, FDG-positron emission tomography(PET), and liver tumor biopsy led to a diagnosis of pancreatic acinar cell carcinoma in the pancreas tail with liver metastasis. The patient was then treated with combination chemotherapy, which consisted of intravenous infusion of GEM and peroral administration of S-1, and the metastatic liver tumor was markedly reduced(partial response in RECIST). Although the prognosis of patients with unresectable pancreatic acinar cell cancers is generally unfavorable, it is suggested that the GEM/S- 1 combination chemotherapy is effective for these patients' treatment.     

A patient with gastric cancer and liver metastases successfully treated with combination chemotherapy including S-1

We report the case of a 62-year-old man with advanced gastric cancer and multiple liver metastases who was successfully treated with combined chemotherapy including S-1. The patient was clinically diagnosed with stage IV (T3 N2 H1 P0) disease and was initially treated with 100 mg/body per day S-1 administered orally for 21 days and 10 mg/body per day cisplatin (CDDP) infused on days 1–5, 8–12, and 15–19. This chemotherapy resulted in significant reduction of the liver and gastric tumors. After receiving additional CDDP/S-1 administration as an outpatient, the patient's liver masses disappeared as shown on abdominal computed tomography (CT). With the patient's desire and informed consent, he underwent curative surgery with total gastrectomy, D1+α lymph node dissection, and partial resection of liver S4. After discharge without any surgical complication, CT revealed regrowth of the S4 liver mass, and combined docetaxel and CDDP was selected as second-line chemotherapy with local radiation therapy against the hepatic metastasis. Additionally, a third regimen with irinotecan and S-1 was given. At 2 years 7 months after the initial treatment, no sign of cancer (including liver metastasis and peritoneal dissemination) has been identified by radiological follow-up examinations.     

A case of elderly non-small cell lung cancer effectively treated by combined chemotherapy of gemcitabine and S-1

The patient was an 86-year-old female who suffered from advanced non-small cell-lung cancer(cT4N3M1, Stage IV). She was treated with combined chemotherapy of gemcitabine and S-1 as first-line therapy. This regimen was performed as a phase I trial for elderly patients with advanced non-small cell lung cancer. The treatment assessment was evaluated as partial response. No toxic events were observed due to this therapy, so she was treated as an outpatient. She was considered to have good quality of life.     

A case of unresectable cholangiocellular carcinoma treated with surgery followed by combination chemotherapy

The patient was a 44-year-old man, who was investigated for lateral abdominal pain and liver dysfunction, and subsequently referred to our department with a diagnosis of unresectable intrahepatic cholangiocellular carcinoma (CCC). Radiological examinations revealed the huge mass in the right lobe of the liver with intrahepatic metastasis in the left lobe. The main tumor was surgically removed, but the metastases were not removed. A month after the operation, a subcutaneous implant reservoir was indwelled for repeated transcatheter hepatic arterial chemo infusion therapy (5-fluorouracil 500 mg/day continuous infusion, day 1-5, and CDDP 10 mg/day, day 1) from the right femoral artery. After 15 courses of home anti-cancer chemotherapy, abdominal CT revealed that the size of intrahepatic metastasis in the left lobe of the liver had not shown growth, whereas other metastitic sites popped up in the caudate lobe, which were free of chemical agent flow. There was no major complication related to the chemotherapy throughout the post-treatment course. Although he maintained a good level of QOL, he refused further chemotherapy due to depression. He died of liver failure 7 months after the operation. In conclusion, volume reduction surgery followed by transcatheter hepatic arterial chemo infusion might be promising as an effective therapy for non resectable CCC.