s-1-(combination) and Gallbladder-Neoplasms

Biliary tract cancers are a group of rare heterogeneous malignant tumours. They include intrahepatic and extrahepatic cholangiocarcinomas, gallbladder carcinomas, and ampullary carcinomas. Surgery remains the optimal modality of therapy leading to long-term survival for people diagnosed with resectable biliary tract carcinomas. Unfortunately, most people with biliary tract carcinomas are diagnosed with either unresectable locally-advanced or metastatic disease, and they are only suitable for palliative chemotherapy or supportive care.. To assess the benefits and harms of intravenous administration of gemcitabine monotherapy or gemcitabine-based chemotherapy versus placebo, or no intervention, or other treatments (excluding gemcitabine) in adults with advanced biliary tract carcinomas.. We performed electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science up to June 2017. We also checked reference lists of primary original studies and review articles manually, for further related articles (cross-references).. Eligible studies include randomised clinical trials, irrespective of language or publication status, comparing intravenous administration of gemcitabine monotherapy or gemcitabine-based combination to placebo, to no intervention, or to treatments other than gemcitabine.. We used standard methodological procedures expected by Cochrane. We assessed risks of bias of the included trials using definitions of predefined bias risk domains, and presented the review results incorporating the methodological quality of the trials using GRADE.. We included seven published randomised clinical trials with 600 participants. All included trials were at high risk of bias, and we rated the evidence as very low quality. Cointerventions were equally applied in three trials (gemcitabine plus S-1 (a combination of tegafur, gimeracil, and oteracil) versus S-1 monotherapy; gemcitabine plus S-1 versus gemcitabine monotherapy versus S-1 monotherapy; and gemcitabine plus vandetanib versus gemcitabine plus placebo versus vandetanib monotherapy), while four trials compared gemcitabine plus cisplatin versus S-1 plus cisplatin; gemcitabine plus mitomycin C versus capecitabine plus mitomycin C; gemcitabine plus oxaliplatin versus chemoradiotherapy; and gemcitabine plus oxaliplatin versus 5-fluorouracil plus folinic acid versus best supportive care. The seven trials were conducted in India, Japan, France, China, Austria, South Korea, and Italy. The median age of the participants in the seven trials was between 50 and 60 years, and the male/female ratios were comparable in most of the trials. Based on these seven trials, we established eight comparisons. We could not perform all planned analyses in all comparisons because of insufficient data.Gemcitabine versus vandetanibOne three-arm trial compared gemcitabine versus vandetanib versus both drugs in combination. It reported no data for mortality, health-related quality of life, or tumour progression outcomes. We rated the increased risk of serious adverse events, anaemia, and overall response rate as very low-certainty evidence.Gemcitabine plus cisplatin versus S-1 plus cisplatinFrom one trial of 96 participants, we found very low-certainty evidence that gemcitabine can lower the risk of mortality at one year when used with cisplatin versus S-1 plus cisplatin (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 0.98; P = 0.04; participants = 96). The trial did not report data for serious adverse events, quality of life, or tumour response outcomes. There is very low-certainty evidence that gemcitabine plus cisplatin combination leads to a higher risk of high-grade thrombocytopenia compared with S-1 plus cisplatin combination (RR 5.28, 95% CI 1.23 to 22.55; P = 0.02; participants = 96).Gemcitabine plus S-1 versus S-1From two trials enrolling 151 participants, we found no difference between the two groups in terms of risk of mortality at one year or risk of serious adverse events. Gemcitabine plus S-1 combination was associated with a higher overall response rat. In adults with advanced biliary tract carcinomas, the effects of gemcitabine or gemcitabine-based chemotherapy are uncertain on mortality and overall response compared with a range of inactive or active controls. The very low certainty of evidence is due to risk of bias, lack of information in the analyses and hence large imprecision, and possible publication bias. The confidence intervals do not rule out meaningful benefits or lack of effect of gemcitabine in all comparisons but one on mortality where gemcitabine plus cisplatin is compared with S-1 plus cisplatin. Gemcitabine-based regimens showed an increase in non-serious adverse events (particularly haematological toxicities). Further randomised clinical trials are mandatory, to further explore the best therapeutic options for adults with advanced biliary tract carcinomas.

Topics: Ampulla of Vater; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Capecitabine; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Male; Mitomycin; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Piperidines; Quinazolines; Randomized Controlled Trials as Topic; Tegafur

Nodal metastasis is a leading attributable factor of poor survival in biliary tract cancer (BTC), and adjuvant chemotherapy targeting this high-risk feature has not been attempted to date. This study aimed to test the efficacy of adjuvant S - 1 for patients with node-positive BTC.. This single-arm multicenter phase 2 trial enrolled patients who underwent resection for histologically proven node-positive BTC. In this trial, S - 1 was administered at a dose of 80-120 mg/day on 14 days of a tri-weekly cycle for 6 months. The primary end point of the trial was 3-year overall survival (OS), in which the result would be promising if the 90% confidence interval (CI) surpassed a threshold of 30% (alpha error, 0.1; beta error, 0.2). The secondary end points were relapse-free survival (RFS), feasibility, and toxicity.. The trial included 50 patients with perihilar (n = 23) or distal (n = 20) cholangiocarcinoma, or gallbladder cancer (n = 7). The median numbers of positive lymph nodes and examined lymph nodes were respectively 2 and 15. The 3-year OS and RFS were respectively 50% (90% CI, 40.9-59.1%) and 32.0% (95% CI, 19.1-44.9%), with median survival times of 34.6 months (95% CI, 19.3-49.8 months) and 18.4 months (95% CI, 11.9-24.9 months). Although hematologic toxicity often occurred, grades 3 and 4 toxicity were rare. The completion rate of the test therapy was 64%, and the median relative dose intensity was 87.5% (interquartile range, 50-100%).. Adjuvant chemotherapy with S - 1 may be promising for patients with node-positive BTC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Chemotherapy, Adjuvant; Cholangiocarcinoma; Disease-Free Survival; Drug Combinations; Gallbladder Neoplasms; Humans; Lymphatic Metastasis; Oxonic Acid; Tegafur; Treatment Outcome

We report a patient with gallbladder cancer and multiple liver and lymph node metastases which completely responded to S-1, an oral fluoropyrimidine anticancer drug. The patient was enrolled in the "Late phase II study of S-1 in patients with advanced biliary tract cancer". A partial response was confirmed after the first two courses of S-1 monotherapy, and anti-tumor efficacy was finally evaluated as a complete response after the 5th course. S-1 was discontinued after the 18th course because of long CR, and the patient has been alive and disease-free for more than 3 years. Grade 2 anorexia, diarrhea, hand-foot skin reaction, and tasty disturbance were observed, but no grade 3 or more toxicities were noted. S-1 appeared to be effective against advanced gallbladder cancer and showed excellent tolerability.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Gallbladder Neoplasms; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC.. 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity.. The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs.. GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Surgical Procedures; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Gallbladder Neoplasms; Gemcitabine; Humans; Klatskin Tumor; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Propensity Score; Survival Rate; Tegafur

Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial.. Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events.. One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing.. UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Bile Duct Neoplasms; Carcinoma; Cholangiocarcinoma; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Gallbladder Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Prospective Studies; Tegafur; Treatment Outcome

Cholecystectomy with gallbladder bed resection and regional lymphadenectomy was performed in a 75-year-old man with advanced gallbladder cancer. Pathological examination revealed adenocarcinoma in the gallbladder with regional lymph node metastases. Cancer recurrence was found in paraaortic lymph nodes behind the duodenum 9 months after the surgery. Although chemotherapy using S-1 was initiated, the lymph nodes remained the same size after 2 courses without any new recurrent regions. Lymphadenectomy was then performed as a curative surgery. The patient has remained alive without recurrence for 46 months after the second surgery.

Topics: Aged; Drug Combinations; Gallbladder Neoplasms; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

Gallbladder cancer (GBC) is a highly fatal malignancy. Due to its invasiveness and delayed diagnosis, many GBC patients are diagnosed with synchronous liver and hepatoduodenal ligament involvement. In our case, we report a gallbladder cancer with portal vein thrombus.. A 60-year-old woman presented with persistent upper abdominal dull pain for 2 months.. Ultrasound examination showed gallbladder carcinoma invading liver segment IV, and a tumor thrombus in the left and right main portal trunk. Ultrasonography and contrast-enhanced magnetic resonance imaging (MRI) showed gallbladder carcinoma with invasion of adjacent liver, and tumor thrombus in the right branch of the portal vein and intrahepatic bile duct. Abdominal computed tomography angiography (CTA) revealed no hepatic artery invasion.. We made a decision to perform extended right lobectomy. Twenty-six days later, the patient underwent intravenous infusion port implantation for S-1 plus oxaliplatin (SOX) therapy.. After treatment, the patient has been doing very well and no recurrence has been found for 5 months.. The patient with gallbladder cancer and tumor thrombus in the portal vein described in this report provides a reminder for surgeons of the importance of early diagnosis, and adequate surgical and adjuvant treatment. Multi-disciplinary treatment is significantly beneficial for the overall survival of patients with advanced GBC.

Topics: Administration, Intravenous; Antineoplastic Agents; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Drug Combinations; Female; Gallbladder Neoplasms; Hepatectomy; Hepatic Artery; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Portal Vein; Tegafur; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Vascular Access Devices; Vascular Neoplasms

The reported patient was a 90-year-old woman with anorexia. She was diagnosed with advanced gallbladder cancer that occurred concurrently with stomach cancer. Subsequent to intestinal bypass surgery, S-1(80mg/day)was administered for 14 days, followed by 7 days of rest for one course. Tumor marker levels returned to normal after 4 months. Computed tomography results indicated that, in regard to the gallbladder cancer, the patient had stable disease after 8 months. In addition, gastroscopy revealed a complete response of the gastric cancer after a year. The patient was able to continue treatment as an outpatient until she experienced aspiration pneumonia. The administration of S-1 was terminated after 4 years and 4 months. Treatment with S-1 monotherapy is considered safe for elderly patients, and has the additional benefit that it is deliverable as an outpatient treatment.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Fatal Outcome; Female; Gallbladder Neoplasms; Humans; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors

An 86-year-old woman underwent a cholecystectomy for gallbladder cancer. Seven months later, an abdominal CT scan showed multiple liver and lymph node metastases. Treatment with S-1 was started at a dose of 100 mg/day, but was changed to alternate-day administration because of diarrhea. Metastatic lesions showed a complete response after 7 months of chemotherapy. S-1 alternate-day therapy could be maintained without any severe adverse events. This method can be managed safely and with certainty in an elderly patient and it has demonstrated efficacy in the treatment of recurrent gallbladder cancer.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gallbladder Neoplasms; Humans; Liver Neoplasms; Lymphatic Metastasis; Oxonic Acid; Recurrence; Tegafur; Treatment Outcome

A 76-year-old woman was referred to our hospital because of an abdominal tumor in September 2009. An irregularly shaped large tumor was detected in the right subcostal abdominal cavity on computed tomography, and was diagnosed as advanced gallbladder cancer without distant metastasis following further examination. We then performed a laparotomy. The tumor had invaded directly into the descending portion of the duodenum and transverse colon. We performed a curative resection of the tumor macroscopically. Pathological findings were moderately differentiated tubular adenocarcinoma derived from gallbladder cancer(T3N0M0, Stage III ). Postoperative antineoplasticc hemotherapy was not administered. At least 4 metastaticregions in the liver(segments 1, 5, 7, and 8)were detected using computed tomography 3 months after the operation, and we then initiated oral administration of S-1. After beginning treatment, we observed partial remission at 3 months and continued treatment. We changed the regimen of chemotherapy to gemcitabine 11 months later because of a drug-induced corneal disorder. One after treatment change also continues advertising, and treatment has ended 5 years after the operation. The patient has not received any treatment for the last 6 years and 7 months, and is now in the follow up period.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Liver Neoplasms; Oxonic Acid; Tegafur; Treatment Outcome

We investigated effects of gemcitabine-based adjuvant chemotherapy (GEM) on prognosis of patients with gallbladder cancer.. We retrospectively analyzed outcomes of 36 patients who underwent radical resection for gallbladder cancer from 2001 through to 2012, using χ(2) for prognostic factors and Kaplan-Meier estimator and log-rank tests for survival data.. The GEM group had higher rates of lymph node positivity and distant metastasis, higher UICC stage and fewer R0 resections; their 5-year survival rate (60%) did not significantly differ from that of the controls (70.0%), nor was GEM a significant prognostic factor in univariate analysis. However, among patients who underwent R1 and R2 resections, GEM significantly improved prognosis in both univariate and multivariate analyses. Median survival of the R1/2 GEM group (66.4 months) was significantly better than that of controls (5.4 months) (p=0.002).. GEM improved prognosis of patients with gallbladder cancer after R1/R2 resections.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Chemotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gallbladder Neoplasms; Gemcitabine; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Survival Rate; Tegafur

A 62-year-old woman diagnosed with gallbladder cancer exhibiting broad liver invasion and metastasis to Couinaud's hepatic segments 4 and 8 (S4 and S8) consulted her regular doctor. Owing to the presence of liver metastases, she received treatment with gemcitabine plus S-1. After four cycles of chemotherapy, the size of the main lesion dramatically decreased and the two liver metastases disappeared. After six cycles of chemotherapy, the patient was referred to our hospital for surgical treatment. Upon admission, there was no evidence of any distant metastasis, based on a detailed radiological examination. Therefore, we performed cholecystectomy and central bisegmentectomy of the liver after obtaining the patient's informed consent. Pathological examination demonstrated viable cancer cells with granuloma formation and calcification in the gallbladder, as well as regenerative changes without viable cancer cells in S4 and S8 of the liver. Gemcitabine plus S-1 was again administered as postoperative adjuvant chemotherapy. One and a half years after the surgery, there were no signs of recurrence. In patients selected according to their response to chemotherapy, surgical treatment might therefore be effective against gallbladder cancer with metastasis.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cholecystectomy; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Tegafur

A 55-year-old man suffering from gastric cancer associated with metastases to the lymph node, gallbladder, and liver was administered chemotherapy with S-1 and cisplatin. Before initiation of therapy, the primary tumor, lymph node metastases, and liver metastases showed fluorodeoxyglucose (FDG) accumulation by positron emission tomography (PET). After 1 course of chemotherapy, the patient received curative surgical treatment including distal gastrectomy, partial hepatectomy, cholecystectomy, and lymph node dissection. The final pathological finding was moderately differentiated adenocarcinoma, T4b(SI), N3a(10/20), P0, CY0, pH1, pM1, Stage IV. Five months after surgery, the serum carcinoembryonic antigen (CEA) level was found to be increasing and PET examination identified an FDG-accumulating nodule in the ascending colon. Colonoscopy identified a submucosal tumor diagnosed as a metastasis from the gastric cancer. Right colectomy was performed 7 months after the first surgery resulting in a curative resection. In each surgery, PET examination indicated that no other distant metastases existed, and curative resection would be possible. Furthermore, although solitary metastatic colorectal lesions are rare, PET examination revealed them accurately. Thus, FDG-PET is very useful for identifying metastases in patients with gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Gallbladder Neoplasms; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

A 59-year-old woman with upper abdominal pain was diagnosed as having an advanced-stage gallbladder carcinoma with significant metastases in the para-aortic lymph nodes to the more distant right external iliac nodes by imaging studies. These findings suggested that the tumor was unresectable, and therefore, palliative cholecystectomy with lymph node biopsy was performed. Furthermore, we initiated chemoradiotherapy with linac radiotherapy( 50 Gy) and weekly gemcitabine (GEM 300 mg/body) for 6 weeks. Partial response (PR) was achieved after chemoradiotherapy. Subsequently, we initiated chemotherapy with GEM alone (1,000 mg/m2) on days 1, 8, and 15, every 28 days for 15 courses. Following disease progression, we initiated chemotherapy with S-1 alone( 80 mg/m2/day) on days 1-14, every 21 days for 9 courses, as second-line treatment. Two years later, following re-progression of the disease, we performed best supportive care with retrograde ureteral stenting for hydronephrosis and retrograde biliary stenting for obstructive jaundice. The patient survived for 35 months after palliative surgery. Moreover, she remained well and performed normal activities for 34 months. This experience indicates that, in patients with unresectable gallbladder carcinoma, multidisciplinary treatment could extend survival and improve the quality of life.

Topics: Antineoplastic Agents; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Quality of Life; Tegafur

Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

Topics: Aged; Aged, 80 and over; Aquaporin 1; Aquaporin 4; Aquaporin 5; Aquaporins; Bile Duct Neoplasms; Biomarkers, Tumor; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Prognosis; Tegafur

A 57-year-old man with advanced gallbladder cancer and accompanying hepatic, colonic and duodenal invasion and para-aortic lymph node metastasis was referred to our hospital. Gemcitabine plus S-1 administration was chosen. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1 and 15, and repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Chemotherapy was effective for the primary gallbladder tumor and lymph node metastasis. The primary tumor and metastatic lymph nodes were shown to have disappeared by a FDG-PET CT study after 10 courses of chemotherapy. Informed consent was obtained prior to performing surgery of the primary lesion. Pathological examination showed fibrosis and a small focus of residual cancer in the resected gallbladder. Complete resection was achieved as all the margins were negative. The findings suggest that gemcitabine plus S-1 treatment may be effective against advanced gallbladder cancer.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Gallbladder Neoplasms; Gemcitabine; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Tegafur

A 66-year-old man was referred to our hospital with obstructive jaundice. Computed tomography(CT)scan showed thickening of the gallbladder wall, invasion into the liver bed, and thickening of the rectal wall. Colonoscopy revealed a type 2 rectal cancer, in which adenocarcinoma was identified by endoscopic biopsy. He was diagnosed with double-cancer of the gallbladder and rectum. Because his gallbladder cancer was more life threatening than his rectal cancer, gemcitabine was administered at 1, 000 mg/m2 on days 1, 8, and 15 of a 28-day course. After 3 courses of gemcitabine, the CT scan showed that the lymph nodes in the hepatoduodenal ligament had been enlarged, and duodenal stenosis had occurred as a result of gallbladder cancer invasion. S-1 was administered orally at doses of 120 mg/day twice daily on days 1-28 of a 42-day course. Partial response was confirmed by CT scan. After 8 courses of S-1, the gallbladder cancer had progressed and liver metastases had appeared. He subsequently died of disease progression. He survived for 17 months after the first course of chemotherapy, and the progression-free survival with S-1 was 10 months. Therefore, S-1 could be an effective agent for synchronous double cancer of the gallbladder and rectum.

Topics: Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Gallbladder Neoplasms; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Salvage Therapy; Tegafur; Tomography, X-Ray Computed

A 67-year-old man visited our hospital for further check-up of biliary tract disease since his two brothers suffered from biliary tract cancer. Abdominal CT scan revealed a wall thickning at the fundus of gallbladder and its vascularity was rich. Chronic cholecystitis was diagnosed, however, cancer was highly suspected. Cholecystectomy was performed and the frozen section of the gallbladder was compatible for cancer. Therefore, segment-4a and -5 liver resections with regeonal lymph node dissection were added. Although preoperative radiological findings were free of liver metastasis, the resected liver specimen included a nodule of 1 cm in segment-5. Extrahepatic bile duct was not resected because the stump of the cystic duct was free from cancer. The final pathological diagnosis according to the TNM classification was pT3N1M1, Stage IV. We considered the patient to be in the high-risk group of recurrence, adjuvant chemotherapy using both gemcitabine and S-1 was performed. S-1 (80 mg/body/day) was scheduled on day 1-14, and gemcitabine (1,000 mg/body) was scheduled on day 8, day 15. The treatment was continued for two years (a total of 28 courses) without experiencing advese events. The patient is cancer free by means of radiological and hematological studies. Gallbladder cancer with liver metastasis in segment-4a and/or -5 can be considered as "local" metastasis, which a liver resection and adjuvant therapy may lead to a good prognosis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Gallbladder Neoplasms; Gemcitabine; Humans; Liver Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Tegafur

We herein report a case of recurrent gallbladder cancer with a remarkable tumor response to S-1 after a failure of gemcitabine (GEM) treatment. A 70-year-old man underwent cholecystectomy and abdominal drainage because of acute cholecystitis and biliary peritonitis. Postoperative pathological diagnosis revealed gallbladder cancer with subserous layer invasion. Subsequently, he had additional radical surgery. After eight months, abdominal CT showed a local tumor recurrence at the hepatic hylum, for which 4 courses of GEM were administered. The therapy was considered ineffective because of the increase in tumor size, and a new lesion in the segment 6 of liver. This led us to change the chemotherapeutic regimen from GEM to S-1. After two courses of S-1, the local recurrent tumor showed a marked decrease in size and liver metastases almost disappeared. The response duration was approximately 8 months, and median survival time from the start of GEM treatment was 17. 5 months. S-1, as a second-line chemotherapeutic drug, produced remarkable local tumor control and most likely survival time with good quality of life in this patient.

Topics: Aged; Drug Combinations; Fatal Outcome; Gallbladder Neoplasms; Humans; Male; Oxonic Acid; Radiography; Recurrence; Tegafur; Tomography Scanners, X-Ray Computed

A 65 -year-old male was admitted to our hospital because of epigastregia. Computed tomography (CT) and abdominal ultrasonography (AUS) revealed advanced gallbladder cancer and two S5 liver metastases. Selective gallbladder angiogram revealed his cystic vein was draining into the portal vein (P5), so cholecystectomy and S4a+S5-subsegmentectomy were performed. Pathological study of the resected specimens showed three liver metastases. After surgical resection lumbar metastasis was suspected, so radiotherapy and UFT at 300mg/day were started. Next, we started oral administration of S-1 alone (100mg/body) for 4 weeks followed by a 2-week rest period as one course. 100mg/day was changed to 80mg/body after 3 courses because of grade 2 neutropenia. A total of 31 courses of S-1 80mg/day were administered postoperatively for five years. The patient is alive and free of disease five years and ten months after the operation.

Topics: Aged; Drug Combinations; Gallbladder Neoplasms; Humans; Liver Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Remission Induction; Tegafur; Tomography, X-Ray Computed

The patient was a 75-year-old woman who had undergone an operation for T4, N0: stage IV a gall bladder cancer in May of 2003. UFT was given as adjuvant chemotherapy. Then S-1 and gemcitabine (GEM) were given because of the recurrence of peritoneal dissemination in June 2006. Though a partial response was maintained, it was judged as progressive disease in July 2007. The peritoneal tumor was solitary, and an operation was performed. S-1 and GEM were given again in January 2008 because of multiple lung metastases. Long-term survival was confirmed until she died of peritonitis carcinomatosa in August 2009. To our knowledge, no case of a long survivor with S-1 and GEM for recurrence after a gall bladder cancer operation has been reported in the literature. Thus, future clinical trials and the accumulation of further cases are warranted.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Fatal Outcome; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Neoplasm Staging; Oxonic Acid; Recurrence; Tegafur; Time Factors; Tomography, X-Ray Computed

We analyzed a treatment outcome and the effect of systemic chemotherapy for patient with unresectable gallbladder carcinoma. Sixteen patients were investigated. Gemcitabine (GEM) was administrated for fifteen patients as the first-line chemotherapy. S-1 was administrated for ten patients as the second-line chemotherapy. The response rate and tumor control rate of the first-line GEM were 14.3% and 78.6%, respectively. The median progression free time of the first-line GEM was 6.0 months. The response rate and tumor control rate of the second-line S-1 were respectively 20.0% and 30.0%. The median progression free time of the second-line S-1 was 1.8 months. The median survival time of all cases was 14.9 months. The outcome of systemic chemotherapy for patients with unresectable gallbladder carcinoma in our hospital was feasible compared with past reports.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Survival Analysis; Tegafur

A 68-year-old man was found to have a gallbladder cancer. Curative operation was impossible because the gallbladder cancer invaded around the gallbladder in CT on 15th of April, 2008. S-1 monotherapy (120 mg/day) was started. S-1 was given orally twice daily for 4 weeks followed by 2 weeks without a treatment. There was no remarkable side effect. The gallbladder cancer was smaller in CT on 25th of September, 2008, and we confirmed a partial response (PR) in CT on 13th of February, 2009. In a pilot phase II study of S-1 for biliary tract cancer, the overall objective response rate was 35.0%. There was no severe side effect. S-1 is one of the effective drugs for biliary tract cancer.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Gallbladder Neoplasms; Humans; Male; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

While surgical resection is the most effective treatment for gallbladder cancer, most of these cancers are not resectable at the time of diagnosis, and therefore, chemotherapy serves as the primary therapy in many cases. However, to date, there is no standard chemotherapy for this cancer. We report a case of advanced gallbladder cancer for which the anticancer drug S-1 was effective. The patient was a 53-year-old woman who presented with a huge ovarian tumor. On workup, all abdominal images revealed the presence of advanced gallbladder cancer that had invaded the liver. Because the gallbladder formed a relatively hard and swollen mass involving the omentum, as revealed during exploration, the surgical resection of the gallbladder was not possible at that time, and only hysterectomy and bilateral salpingo-oophorectomy were performed. She started on the anticancer drug S-1 just after this operation. S-1 is a prodrug of 5-fluorouracil (5-FU), and contains 5-chloro-2-4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase (DPD) that rapidly degrades 5-FU. Eight months after the first operation, radical cholecystectomy was performed. Pathologically, the tumor was diagnosed as an adenocarcinoma of the gallbladder, and no evidence of liver invasion was found. Intratumoral gene expression analysis of the resected gallbladder revealed significantly elevated DPD expression. We suggest that the rapid degradation of 5-FU mediated by this high DPD in our patient was significantly blocked by the CDHP in S-1, and that the efficacy of 5-FU was consequently maintained at the maximum level.

Topics: Antimetabolites, Antineoplastic; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Fluorouracil; Gallbladder Neoplasms; Humans; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The patient was a 64-year-old woman. Oral S-1 and hepatic arterial infusion (HAI) of low-dose CDDP therapy were started for unresectable advanced gallbladder cancer associated with liver metastasis and numerous lymph node metastases. Marked regression of the liver metastasis and lymph node metastases was observed by this treatment, and upon completion of the second course they had almost completely resolved. The tumor marker values also converted to negative. We report a case in which oral S-1 and HAI of low-dose CDDP therapy was effective against advanced gallbladder cancer associated with liver metastasis and multiple lymph node metastases.

Topics: Administration, Oral; Angiography; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Drug Combinations; Female; Gallbladder Neoplasms; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

We described a case with recurrent gallbladder carcinoma, successfully treated by combination chemotherapy using gemcitabine, CPT-11, and S-1 that was administered as second-line chemotherapy after failure of gemcitabine monotherapy. The level of CA19-9 was normalized three months later, and metastatic tumors of the liver were calcified. She had received the combination chemotherapy for 15 months and is now alive.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Calcinosis; Camptothecin; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Irinotecan; Liver Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

A 53-year-old woman was revealed to have gallbladder cancer with liver metastases (H 1). Since a curative operation is impossible in this case, we started systemic chemotherapy employing S-1 combined with hepatic arterial infusion using epirubicin hydrochloride and mitomycin C. After three months, the primary lesion was reduced in size. The patient has been receiving systemic chemotherapy using S-1 only as an outpatient for 16 months. Although there is not enough evidence to support standard treatment, systemic chemotherapy combined with hepatic arterial infusion would improve the survival time without deterioration of quality of life in patients with advanced gallbladder cancer. This combined therapy should be considered one of the promising strategies for advanced gallbladder cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Epirubicin; Female; Gallbladder Neoplasms; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Middle Aged; Mitomycin; Oxonic Acid; Remission Induction; Tegafur

We experienced a case of advanced gallbladder cancer with a remarkable response treated by oral fluoropyrimidine anticancer drug S-1 (120 mg/day on day 1 through 28 followed by a 14-day recovery period) as first-line chemotherapy. The patient was enrolled in the late phase II trial of S-1 for metastatic biliary tract cancer designed to evaluate efficacy and safety. The anti-tumor effect was observed in both primary lesion of gallbladder and metastatic lesion of liver,and the efficacy was confirmed to be a partial response (Japan Society for Cancer Therapy Criteria). After the first two courses of treatment, the reduction ratio of the tumor volume was 88.1% in the measurable lesions of liver metastasis. No severe adverse event was noted except grade 3 desquamation. The patient continued the outpatient treatment for a total 7 courses. The overall survival time was 470 days,suggesting that S-1 is highly effective and tolerable for metastatic gallbladder cancer.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Gallbladder Neoplasms; Humans; Liver Neoplasms; Male; Oxonic Acid; Quality of Life; Tegafur

A 76-year-old man suffering from advanced gallbladder cancer after hepato-pancreaticoduodenectomy had cholangitis and serum elevation of CA19-9 2 years and 6 months after the operation. A recurrent tumor had been recognized from the hilar to the surrounding inferior vena cava, and stenosis of jejunum utilized for pancreaticocholedoco-jejunostomy. A bypass operation of jejunum was performed. Combination chemotherapy with TS-1 100 mg/day (3 weeks) and CDDP 30 mg/day (day 1, 8 drip infusion) in 1 course was performed, and a partial response (PR) was noted. Diarrhea of grade III and decreased WBC of grade II were recognized, and were improved. Two courses of the same chemotherapeutic regimen were carried out. Among 5 months, recurrent tumor showed preservation of PR. Into 3 course of chemotherapy, radiation therapy was selected for second opinion. But recurrent tumor was enlarged acutely, and radiation therapy was stopped. He died 15 months after the first detection of chemotherapy. The combination chemotherapy of TS-1 and CDDP seems to be beneficial therapy for advanced gallbladder cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Gallbladder Neoplasms; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Pancreaticojejunostomy; Pyridines; Tegafur

TS-1 is reported to be beneficial for advanced gastric cancer, but there is no report on its use for advanced gallbladder cancer. The present patient was a 64-year-old woman with advanced gallbladder cancer with severe biliary tract stenosis. The primary tumor was located in the neck of the gallbladder and peripancreatic lymph node metastasis was detected. TS-1 100 mg/day was administered orally for 21 days and CDDP 30 mg/day on days 1, 8 by drip infusion. Grade 4 neutropenia was observed in the first cycle, and TS-1 alone was used for further treatment. After 2 courses, primary tumor showed PR and lymph node metastasis had disappeared. Biliary stenosis was remarkably improved. We conclude that TS-1 might be beneficial in the treatment of advanced gallbladder cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Diseases; Cisplatin; Constriction, Pathologic; Drug Administration Schedule; Drug Combinations; Female; Gallbladder Neoplasms; Humans; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Tegafur