Survival Outcomes of Gemcitabine Plus S-1 Adjuvant Chemotherapy after Surgical Resection for Advanced Biliary Tract Cancer

Oncology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Kiyotaka Hosoda ◽  
Kentaro Fukushima ◽  
Akira Shimizu ◽  
Hiroaki Motoyama ◽  
Koji Kubota ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Surgical Resection ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Matched Pairs ◽  
Adjuvant Setting ◽  
Curative Surgery ◽  
Free Survival ◽  
Tract Cancer ◽  
Grade 3

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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/m<sup>2</sup> oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m<sup>2</sup> 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. <b><i>Results:</i></b> 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%, <i>p</i> = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, <i>p</i> = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs. <b><i>Discussion/Conclusion:</i></b> GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence.

A prospective randomized controlled trial comparing 4-weekly versus 3-weekly adjuvant chemotherapy with gemcitabine after curative resection of biliary tract cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 345-345
Author(s):  
Shin Nakahira ◽  
Shogo Kobayashi ◽  
Atsushi Miyamoto ◽  
Junzo Shimizu ◽  
Masaki Kashiwazaki ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Controlled Trial ◽  
Survival Rates ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Tract Cancer ◽  
Dose Modifications

345 Background: Resection of biliary tract cancer, employing pancreatoduodenectomy and major hepatectomy, is highly aggressive. Thus, postoperative gemcitabine cannot be administered employing a routine dosage protocol. We theorized that a 3-weekly protocol (days 1 and 8, every 3 weeks) of gemcitabine as adjuvant chemotherapy would be superior to the usually administered 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Methods: The outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol were compared in a prospective randomized clinical setting. The primary endpoint was the treatment completion rate, while secondary endpoints were adverse events and recurrence-free survival. Results: We enrolled a total of 27 patients. Only two patients (14%) on the 4-weekly protocol and three (23%) on the 3-weekly protocol (p=0.8099) completed treatment with no omissions and/or dose modifications. Most of the remaining patients (70%) experienced grade 3/4 neutropenia. Relative dose intensities were 72% and 78%, respectively, with the 4-weekly and 3-weekly protocols. Recurrence-free survival rates did not differ significantly between the two protocols. Conclusions: Contrary to our hypothesis, the 3-weekly protocol did not produce superior results in terms of completion, adverse events or recurrence-free survival rates as compared to the standard 4-week protocol.

scholarly journals Anti-PD-1 therapy combined with chemotherapy in patients with advanced biliary tract cancer

2019 ◽  
Vol 68 (9) ◽  
pp. 1527-1535 ◽  
Author(s):  
Danyang Sun ◽  
Junxun Ma ◽  
Jinliang Wang ◽  
Chun Han ◽  
Yuanyu Qian ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Primary Outcome ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Combination Group ◽  
Free Survival ◽  
Tract Cancer ◽  
Previously Treated ◽  
Grade 3

Abstract Background Evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. Methods Chinese BTC patients receiving a PD-1 inhibitor with chemotherapy, PD-1 inhibitor monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcomes were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T cell costimulation or immune checkpoints were excluded. Results The study included 77 patients (a PD-1 inhibitor plus chemotherapy, n = 38; PD-1 inhibitor monotherapy, n = 20; chemotherapy alone, n = 19). The median OS was 14.9 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 4.1 months with PD-1 inhibitor monotherapy (HR 0.37, 95% CI 0.17–0.80, P = 0.001) and the 6.0 months with chemotherapy alone (HR 0.63, 95% CI 0.42–0.94, P = 0.011). The median PFS was 5.1 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 2.2 months with PD-1 inhibitor monotherapy (HR 0.59, 95% CI 0.31–1.10, P = 0.014) and the 2.4 months with chemotherapy alone (HR 0.61, 95% CI 0.45–0.83, P = 0.003). Grade 3 or 4 treatment-related adverse events were similar between the anti-PD-1 combination group and the chemotherapy alone group (34.2% and 36.8%, respectively). Conclusions Anti-PD-1 therapy plus chemotherapy is an effective and tolerable approach for advanced BTC.

Feasibility and potential benefits of adjuvant chemotherapy with S-1 in patients with curative resected advanced biliary tract cancer: A multicenter trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15179-e15179
Author(s):  
Yoshikazu Toyoki ◽  
Keinosuke Ishido ◽  
Daisuke Kudo ◽  
Norihisa Kimura ◽  
Taiichi Wakiya ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Performance Status ◽  
Disease Free Survival ◽  
Radical Resection ◽  
Multicenter Trial ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Grade 3

e15179 Background: S-1 chemotherapy is reported to be effective for treating metastatic and unresectable biliary tract cancer (BTC). We assessed the safety and feasibility of adjuvant S-1 chemotherapy in patients with curative resected advanced BTC. Methods: Patients with pathological stage II, III, or IVa BTC (according to JSBS) who underwent radical resection received oral S-1 (80 mg/m2/day) for 2 consecutive weeks every 3 weeks (1 cycle). Patients were aged 20–80 years, had a performance status of <1, and provided informed consent. The treatment was repeated until 1 year after surgery. The primary endpoint was feasibility of the adjuvant chemotherapy with S-1. The secondary endpoints were safety, disease-free survival (DFS), and overall survival (OS). Results: We enrolled 40 patients, but 5 patients were excluded on the basis of eligibility criteria (4 patients) or no drug administration (1 patient). We analyzed data from 35 patients (29 men and 6 women with a median age of 68 years) between January 2009 and November 2011. The feasibilities of 6-month and 12-month administration of S-1 were 65.7% (95% confidence interval [CI]: 47.8–80.9%) and 45.7% (95% CI 28.8–63.4%), respectively. Grade 3 neutropenia and anemia were observed in 2.9% and 5.7% of cases, respectively. Grade 3 non-hematological toxicities included anorexia in 14.3%, fatigue in 8.6%, and nausea in 2.9% of cases. No grade 4 hematological or non-hematological toxicities were observed, and no treatment-related deaths occurred. The 1-year OS was 91.4% (95% CI: 76.6–97.2%), and the 1-year DFS was 68.6% (95% CI: 51.7–81.7%). Conclusions: Adjuvant chemotherapy with S-1 for curative resected advanced BTC patients was both safe and feasible. Although the follow-up period was insufficient to evaluate OS and DFS, adjuvant chemotherapy with S-1 is believed to have improved the prognosis.

Clinical Outcomes of Salvage Chemoradiotherapy for Locally Recurrent Biliary Tract Cancer

2017 ◽  
Vol 103 (4) ◽  
pp. 345-352
Author(s):  
Jeong Il Yu ◽  
Hee Chul Park ◽  
Do Hoon Lim ◽  
Joon Oh Park ◽  
Young Suk Park ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Clinical Outcomes ◽  
Surgical Resection ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Chemotherapy Regimen ◽  
Significant Prognostic Factor ◽  
Free Survival ◽  
Tract Cancer ◽  
Locally Recurrent

Purpose The purpose of this study was to investigate the clinical outcomes and prognostic factors of concurrent chemoradiotherapy (CCRT) for locally recurrent biliary tract cancer (BTC) after curative surgical resection. Methods We performed a retrospective cohort study of patients with locally recurrent BTC treated with CCRT between October 2004 and December 2013. The study included and analyzed 42 patients with a history of curative-intent surgical resection of confirmed adenocarcinoma originating from the biliary tract. Results The median time to recurrence after surgery was 16.1 months (range, 4.5-77.8 months). Median follow-up after CCRT was 26.9 months (range, 5.2-81.9) with no grade 3 or higher gastrointestinal toxicities. Analysis of the first site of failure showed local progression (LP) developed in 20 patients (47.6%); among these, 16 (38.1%) had isolated LP. The median values were 15.8 months (range, 1.7-81.7) for LP-free survival (LPFS), 10.6 months (range, 1.7 - 81.7) for progression-free survival (PFS) and 41.2 months (range, 5.2-81.9) for overall survival (OS). Multivariate analysis showed that the level of pre-CCRT carbohydrate antigen (CA) 19-9 and the chemotherapy regimen were significant prognostic factors for LPFS and PFS; pT stage was the only significant prognostic factor for OS. Conclusions CCRT for locally recurrent BTC showed promising outcomes as a salvage modality, but LP was still frequent. The pre-CCRT CA 19-9 level and the chemotherapy regimen were prognostic factors for LPFS and PFS.

Sex difference in patients with biliary tract cancer receiving chemotherapy: Post hoc analysis of ABC-01, -02, -03, -04, BILCAP.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 517-517
Author(s):  
Eiichiro Suzuki ◽  
John A. Bridgewater ◽  
Juan W. Valle ◽  
John Neil Primrose ◽  
Anna Dorothea Wagner ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Hoc Analysis ◽  
Tract Cancer ◽  
Grade 3 ◽  
Post Hoc

517 Background: The relationship between toxicity from chemotherapy and clinical outcome in biliary tract cancer (BTC) is uncertain. Aim: This post hoc analysis evaluated differences by sex in the frequency of adverse events (AEs) and overall survival (OS) and its impact on progression-free survival (PFS)/recurrence-free survival (RFS) for BTC patients. Methods: Individual patient data were retrieved from ABC -01, -02, -03, -04, and BILCAP study. AEs were graded according to National Cancer Institute's Common Toxicity Criteria v 4.02 and odds ratios along with 95%CI and p-values derived from logistic regression were used to assess the effect of sex on the risk of AEs. Time to event outcomes were evaluated using Cox regression and plotted using Kaplan-Meier plots. All statistical tests were two-sided. Results: Overall 994 patients-data were examined: 86 in ABC-01, 324 in-02, 124 in -03, 13 in -04 and 447 in BILCAP. A total of 484 (49%) were males (M) and 510 (51%) were females (F). 770 patients were evaluable for AEs because a total of 224 patients in BILCAP study belonged to the observation group. Urinary tract infection (M, 1.6%; F, 5.5%), nausea (M, 50.7%; F, 69.9%), vomiting (M, 29.1%; F, 46.1%), alopecia (M, 11.3%; F, 27.3%), are dominant in F, hyperbilirubinaemia (M, 36.7%; F, 29.1%) and thrombocytopenia (M, 43.1%; F, 34.3%) and hiccups (M, 2.4%; F, 0.5%) are dominant in M at any grade. Vomiting (M, 3.5%; F, 7.0%) and fatigue (M, 4.0%; F, 8.5%) are higher in F than in M for grade 3-5. The median OS (M, 16.2 months (Mo); F, 17.5 Mo), PFS (M, 6.4 Mo; F, 6.5 Mo) and RFS (M, 20.8 Mo; F 19.4 Mo) were similar. Amongst the subgroup of patients with gallbladder, F achieved longer OS (M, 11.5 Mo; F 13.3 Mo, 0.73 (95%CI:0.54,0.99), p = 0.041) and RFS than M (M, 20.8 Mo; median PFS for F not reached, HR:0.52 (95%CI:0.27,1.02), p = 0.057). Conclusions: Females with BTC have tended to have more AEs, especially grade 3+. Although no difference was observed in OS, PFS, and RFS between males and females for the overall cohort of patients, females with gallbladder cancer had an improved OS and RFS compared with males. These findings suggest, in BTC, sex may play a role when designing clinical trials as well as in making treatment decisions.

Feasibility study of postoperative adjuvant chemotherapy with S-1 in patients with biliary tract cancer

2018 ◽  
Vol 23 (5) ◽  
pp. 894-899 ◽  
Author(s):  
Kohei Nakachi ◽  
Masaru Konishi ◽  
Masafumi Ikeda ◽  
Kazuaki Shimada ◽  
Takuji Okusaka ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Biliary Tract ◽  
Feasibility Study ◽  
Biliary Tract Cancer ◽  
Postoperative Adjuvant Chemotherapy ◽  
Tract Cancer

scholarly journals Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial

2020 ◽  
Vol 122 (5) ◽  
pp. 634-639 ◽  
Author(s):  
Ali Belkouz ◽  
Judith de Vos-Geelen ◽  
Ron A. A. Mathôt ◽  
Ferry A. L. M. Eskens ◽  
Thomas M. van Gulik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Salvage Treatment ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Tract Cancer ◽  
Grade 3

Abstract Background No standard treatment is available for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin (GEMCIS). The objective of this study was to evaluate safety and anti-tumour activity of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as salvage treatment in patients with previously treated advanced BTC. Methods In this two-stage phase 2 study, patients with advanced BTC who had disease progression or unacceptable toxicity after ≥3 cycles of GEMCIS were eligible. Primary endpoints were safety and efficacy (defined as objective response rate, ORR). In stage one, ten patients were treated with FOLFIRINOX every 2 weeks. In stage two, an additional 20 patients were enrolled at a starting dose as defined in stage one, provided that in stage ≥1 objective response or ≥2 stable diseases were observed and ≤3 patients had serious adverse events (SAEs) within the first 6 weeks of treatment. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results Forty patients were screened for eligibility and 30 patients were enrolled. In stage one, one patient had a partial response and five patients had stable disease. One patient had a SAE during the first 6 weeks of treatment, and five patients required a dose reduction due to adverse events. The most common grade 3–4 adverse events in stage one were neutropaenia, mucositis and diarrhoea. Stage two was initiated with FOLFIRINOX in an adapted dose. In stage two, grade 3–4 neutropaenia, diarrhoea, nausea and vomiting were the most common adverse events. The ORR, median PFS and OS in all patients were 10%, 6.2 and 10.7 months, respectively. Conclusions In patients with advanced BTC who progressed after or were intolerant to GEMCIS, FOLFIRINOX can be administered safely and could be considered as an option for salvage treatment in these patients. Clinical trial registration ClinicalTrials.gov Identifier NCT02456714.

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