s-1-(combination) and Common-Bile-Duct-Neoplasms

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

An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC.. The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated.. The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC.. BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens.

Topics: Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biliary Tract Surgical Procedures; Biomarkers, Tumor; Biopsy, Needle; Chemotherapy, Adjuvant; Cohort Studies; Common Bile Duct Neoplasms; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Genes, bcl-2; Humans; Immunohistochemistry; Japan; Kaplan-Meier Estimate; Male; Membrane Proteins; Middle Aged; Oxonic Acid; Predictive Value of Tests; Prognosis; Proto-Oncogene Proteins; Rare Diseases; Retrospective Studies; Risk Assessment; Survival Analysis; Tegafur; Thymidylate Synthase

Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis.. Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients.. Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013).. Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Ampulla of Vater; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Pancreaticoduodenectomy; Prognosis; Proportional Hazards Models; Retrospective Studies; Tegafur; Telomerase; Young Adult

A 70-year-old female patient underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in March 2007. In April 2009, multiple lung metastases were detected by CT scanning. The patient was treated with S-1 (80mg/day, day 1-28, followed by 2-weeks withdrawal)from April 2009. The shrinkage of lung metastases was diagnosed as a complete response based on the Response Evaluation Criteria in Solid Tumors(RECIST). No severe toxicities were observed. S-1 is an effective and safe anti-cancer agent available for lung metastases of carcinoma of the ampulla of Vater.

Topics: Aged; Ampulla of Vater; Antimetabolites, Antineoplastic; Common Bile Duct Neoplasms; Drug Combinations; Duodenal Neoplasms; Female; Humans; Lung Neoplasms; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Tomography, X-Ray Computed

We report a case of advanced ampullary carcinoma with para-aortic lymph node metastasis, which showed a complete response to S-1. The patient underwent cholecystectomy and Roux-en-Y choledochojejunostomy, and was then given S-1 orally 80 mg daily for 14 days, followed by 7 days of rest. After four cycles of the S-1 chemotherapy, both the tumor and the swollen paraaortic lymph node had completely disappeared. An additional six cycles were given at the request of the patient. No adverse effects were seen during the S-1 chemotherapy, and the patient has been free of the disease for the 27 months since its completion. Thus, S-1 monotherapy may be considered as a chemotherapeutic strategy for unresectable ampullary carcinoma, although large-scale studies will be required to confirm its true efficacy.

Topics: Ampulla of Vater; Antimetabolites, Antineoplastic; Cholecystectomy; Choledochostomy; Common Bile Duct Neoplasms; Drug Combinations; Humans; Oxonic Acid; Tegafur; Treatment Outcome

We report a case of recurrent carcinoma of the ampulla of Vater with multiple lung and abdominal lymph node metastases that well responded to S-1, an oral fluoropyrimidine. A 56-years-old woman underwent a pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in October 2003. Multiple lung metastases were detected by chest X-ray as a post operative screening a year after surgery. Computed tomography showed multiple abdominal lymph node metastases. The patient was treated with S-1 (80 mg/day, day 1-28, followed by 2 weeks rest) from November 2003. Anti-tumor efficacy was confirmed to be partial response by Response Evaluation Criteria in Solid Tumors (RECIST). Leukocytopenia, anemia, and mucositis were observed. Every toxicity was mild to moderate, and no other severe toxicities were noted. S-1 might be an effective and safe agent for carcinoma of the ampulla of Vater.

Topics: Ampulla of Vater; Antimetabolites, Antineoplastic; Common Bile Duct Neoplasms; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Tegafur