The influence of renal function on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 368-368
Author(s):  
Makoto Ueno ◽  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Gakuto Ogawa ◽  
Yuya Sato ◽  
...  
Keyword(s):  
Renal Function ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Grade 3 ◽  
The Impact

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr > 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 > CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.

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.

Phase II study of gemcitabine, oxaliplatin in combination with bevacizumab (GEMOX-B) in patients with unresectable or metastatic biliary tract and gallbladder cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4625-4625 ◽  
Author(s):  
J. W. Clark ◽  
J. A. Meyerhardt ◽  
D. V. Sahani ◽  
S. Namasivayam ◽  
T. A. Abrams ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Fdg Pet ◽  
Poor Prognosis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Whole Body ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Clinically Significant ◽  
Grade 3

4625 Background: Patients (Pts) with unresectable or metastatic biliary tract cancer (BTC) and gallbladder cancer (GBC) have a poor prognosis. Vascular endothelial growth factor (VEGF) expression has been detected in BTC and GBC. Increased angiogenesis has been correlated with advanced stage of disease and poor prognosis. Given reported activity of gemcitabine (GEM) and oxaliplatin (OX) in BTC/GBC and potential benefits of targeting the VEGF pathway with bevacizumab (B), we performed a study to examine the efficacy and tolerability of GEM, OX and B (GEMOX-B) in unresectable or metastatic BTC/GBC. Methods: Eligibility criteria included unresectable or metastatic measurable BTC/GBC, 0–1 prior chemotherapy regimens, performance status = 2, and adequate organ function. No clinically significant cardiovascular disease or history of active bleeding. Pts were treated with all 3 drugs intravenously on days 1 and 15 every 28 days (one cycle): B was given first at 10 mg/kg, followed by GEM at 1000 mg/m2 as dose rate infusion at 10 mg/m2/minute, and OX at 85 mg/m2. Whole body FDG-PET scan was obtained at baseline and after cycle 2. The primary endpoint of the study was progression-free survival (PFS). Results: 19 pts (10 BTC and 9 GBC) have been enrolled since May 17, 2006: median age = 69 (25–82), M/F = 13/6, ECOG 0/1/2 = 7/10/2. Treatment has been well tolerated with no grade 4–5 toxicities seen. Treatment related grade 3 toxicities included (number of pts): hypertension (2), neutropenia (1), transient SGPT elevation (1), proteinuria (1), neuropathy (1), and fatigue (1). Of 11 pts followed for at least 4 months, 3 had confirmed partial responses (PR), 5 had stable disease (SD) of at least 4 cycles, and 3 had progressive disease (PD) per RECIST criteria. Five pts had more than 50% decrease in CA19–9 levels. Of 16 PET studies analyzed, changes in SUV values from baseline to after 2 cycles of treatment were: 11 PRs, 4 SDs, 1 PD per EORTC criteria. Conclusions: GEMOX-B can be safely administered with tolerable safety profiles in patients with advanced BTC/GBC. Early evidence of antitumor activity was seen. A decreased SUV in FDG-PET following GEMOX-B treatment was observed in the majority of patients. No significant financial relationships to disclose.

Randomized phase II trial of gemcitabine plus S-1 combination therapy versus S-1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 255-255 ◽  
Author(s):  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Junki Mizusawa ◽  
Atsuo Takashima ◽  
Makoto Ueno ◽  
...  
Keyword(s):  
Survival Time ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
Correct Selection ◽  
Biliary Duct ◽  
Phase Iii Trial ◽  
Tract Cancer ◽  
Subsequent Phase ◽  
Grade 3

255 Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Methods: Chemotherapy-naive patients with recurrent or unresectable BTC (gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0 - 1, and adequate organ function were randomly assigned to receive GS (gemcitabine: 1000 mg/m2, iv, days 1 and 8; S-1: 60 mg/m2, p.o., days 1 - 14, every 3 weeks) or S-1 (80 mg/m2, p.o., days 1 - 28, every 6 weeks). We assumed that %1-year survival of one regimen is 30% and that of the other regimen is more than 40%. To ensure at least 85% probability of correct selection, 98 eligible pts are required. The decision rule was that the regimen with higher %1-year survival will be considered as more promising regimen. Results: From February 2009 to April 2010, 101 pts (GB, n=38; IHBD, n=35; EHBD, n=20; AV, n=8) were randomized (GS, n=51; S-1, n=50). For the GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI 0.54-1.36]; p=0.52), and the median progression-free survival time were 7.1 and 4.2 months (0.44 [0.29-0.67]; p<0.0001). Grade 3/4 hematological toxicities were more frequent in the GS arm than in the S-1 arm, (percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia, 29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively. Although two treatment-related deaths occurred in the GS arm (pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological toxicities were infrequent and reversible in both arms. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.

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.

Randomized phase II trial of gemcitabine plus S−1 combination therapy versus S−1 in advanced biliary tract cancer: Results of the Japan Clinical Oncology Group study (JCOG0805).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4031-4031
Author(s):  
Makoto Ueno ◽  
Takuji Okusaka ◽  
Junki Mizusawa ◽  
Atsuo Takashima ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Survival Time ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
Correct Selection ◽  
Biliary Duct ◽  
Phase Iii Trial ◽  
Tract Cancer ◽  
Subsequent Phase ◽  
Grade 3

4031 Background: Gemcitabine plus cisplatin combination (GC) therapy is the standard therapy for advanced biliary tract cancer (BTC). In previous trials, gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had shown considerable efficacy in patients with BTC. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen for a subsequent phase III trial. Methods: Chemotherapy-naive patients with recurrent or unresectable BTC (gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0 - 1, and adequate organ function were randomly assigned to receive GS (gemcitabine: 1,000 mg/m2, iv, days 1 and 8; S-1: 60 mg/m2, p.o., days 1 - 14, every 3 weeks) or S-1 (80 mg/m2, p.o., days 1 - 28, every 6 weeks). We assumed that %1-year survival of one regimen is 30% and that of the other regimen is more than 40%. To ensure at least 85% probability of correct selection, 98 eligible pts are required. The decision rule was that the regimen with higher %1-year survival will be considered as more promising regimen. Results: From February 2009 to April 2010, 101 pts (GB, n=38; IHBD, n=35; EHBD, n=20; AV, n=8) were randomized (GS, n=51; S-1, n=50). For the GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI 0.54-1.36]; p=0.52), and the median progression-free survival time were 7.1 and 4.2 months (0.44 [0.29-0.67]; p<0.0001). Grade 3/4 hematological toxicities were more frequent in the GS arm than in the S-1 arm, (percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia, 29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively. Although two treatment-related deaths occurred in the GS arm (pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological toxicities were infrequent and reversible in both arms. Conclusions: The GS arm was superior in %1-year survival to S-1. Here we consider GS to be more promising as the test arm for a subsequent phase III trial comparing with GC.

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.

Effectiveness study of gemcitabine, oxaliplatin, and capecitabine as first-line treatment for nonresectable biliary tract cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 334-334
Author(s):  
Lars Henrik Jensen ◽  
Anne Haahr Mellergaard ◽  
Dan Hoegdall ◽  
Ole Larsen
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Pivotal Phase ◽  
Tract Cancer ◽  
Gemcitabine And Cisplatin

334 Background: Since 2010, the doublet gemcitabine and cisplatin has been standard first-line systemic treatment for non-resectable biliary tract cancer. In a phase I-II trial of the well-tolerated triplet of gemcitabine, oxaliplatin, and capecitabine, the median progression free survival (PFS) and overall survival (OS) were 6.9 and 12.5 months, respectively. Overall response rate was 34%. Since 2005 the regimen has been used in Denmark. We wanted to investigate the effectiveness of the triplet regimen given in daily clinic. Methods: We included 192 patients from two institutions. Patients had to have non-resectable biliary tract cancer and to be suitable for combination chemotherapy on doctor’s discretion. Gemcitabine 1000 mg/m2 and oxaliplatin 60 mg/m2 were given every two weeks followed by capecitabine 1000 mg/m2 b.i.d. for one week. At one institution the oxaliplatin dose was 50 mg/m2 and capecitabine dose 650 mg/m2 b.i.d. continuously. One cycle included two treatments and was typically administered for up to six cycles/months, but was allowed for longer time until progression. Results: At institution A, 117 patients were included and 73 (62%) were women. Median age was 66 years (range 25-80). Median treatment duration was six cycles/months (range 1-12). Thirty-five, 69, 12, and one patient(s) were in performance status 0, 1, 2, and 3, respectively. Ninety patients were evaluable for response and 6 (7%) had complete response, 18 (20%) partial response, 53 (59%) stable disease, and 13 (14%) progression as best response. Median PFS was 9.7 months (95% CI 8.5-11.7) and median OS 11.7 months (9.8-14.0). The results were comparable to institution B, where the response rate in 56 patients with measurable disease was 30%. In 75 patients evaluable for survival analysis, PFS was 8.1 months and OS 12.0 months for performance status 0-1 (n=55). Patients in performance status 2 (n=25) had a PFS and OS of only 1.7 and 2.8 months, respectively. Conclusions: A triplet of gemcitabine, oxaliplatin, and capecitabine given in daily clinic was well tolerated and has effectiveness comparable to results from a phase II trial and the pivotal phase III trial of gemcitabine and cisplatin.

Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 225-225 ◽  
Author(s):  
Julien Edeline ◽  
Franck Bonnetain ◽  
Jean Marc Phelip ◽  
Jérôme Watelet ◽  
Pascal Hammel ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Tract Cancer ◽  
Post Surgery ◽  
Significant Difference ◽  
Grade 3

225 Background: No standard post-surgery adjuvant treatment is currently recommended in localized biliary tract cancer (BTC). Gemcitabine combined with platinum is the standard chemotherapy for advanced BTC. The aim of this phase III randomized trial was to assess whether GEMOX would increase relapse-free survival (RFS) while maintaining health-related quality of life (HrQoL). Methods: We performed a multicenter randomized phase III trial. Patients were randomized, within 3 months of R0 or R1 resection of a localized BTC (intra-hepatic, perihilar, extra-hepatic cholangiocarcinoma or gallbladder cancer), to receive either GEMOX 85 for 12 cycles (Experimental Arm A) or surveillance (Standard Arm B). Co-primary objectives were RFS and HrQoL. 190 patients and 126 RFS events were required to show an increase of median RFS from 18 to 30 months. Results: Between July 2009 and February 2014, 196 patients were included in 33 French centers. Baseline characteristics were balanced, with similar primary sites, R0 resection rates were 86.2% (Arm A) vs 87.9% (Arm B), lymph node invasion present in 37.2% vs 36.4%. In Arm A, a median of 12 cycles was delivered (mean: 9.3, range: 0-12). Maximal grade of adverse events were grade 3 in 57.5% vs 22.2%, and grade 4 in 17.0% vs 9.1%. During treatment one patient died in each arm. The main grade ≥ 3 adverse events in the year following inclusion were peripheral neuropathy (50.0% vs 1.1%), and neutropenia (22.3% vs 0%). Median follow-up was 44.3 months, with 54 and 64 RFS events in arms A vs B. There was no significant difference in RFS between the arms (log-rank p = 0.31), with a hazard ratio of 0.83 [95% CI: 0.58-1.19], p = 0.31 (futility boundaries were crossed). Median RFS was 30.4 [95% CI: 15.4-45.8] vs 22.0 months [95%CI: 13.6-38.3] in arms A & B respectively, and 4-years RFS was 39.3% [95%CI: 28.4%-50.0%] vs 33.2% [95%CI: 23.1-43.7%]. Global Health HrQoL scores were not different at 12 months (70.8 vs 83.3, p = 0.18) and at 24 months (75.0 vs 83.3, p = 0.50). Conclusions: Adjuvant chemotherapy in BTC with GEMOX was feasible and associated with expected toxicities and no deterioration of HrQoL. There was no significant difference in RFS between GEMOX and surveillance. Clinical trial information: NCT01313377.

A phase II trial of modified gemcitabine plus S-1 combination as the first-line treatment in patients with advanced biliary tract cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 417-417
Author(s):  
Nai-Jung Chiang ◽  
Jen-Shi Chen ◽  
Ming-Huang Chen ◽  
Shih-Hung Yang ◽  
Chiun Hsu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Null Hypothesis ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standard Regimen ◽  
Tract Cancer ◽  
To Receive

417 Background: Gemcitabine plus platinum, notably cisplatin, is conceived as the standard regimen for advanced biliary tract cancer (ABTC) nowadays. Recent randomized phase II study (JCOG0805) showed that gemcitabine plus S-1 was more promising than S-1 alone in ABTC, and a randomized phase III, UMIN 000001685, is currently ongoing to compare the efficacy of gemcitabine plus either S-1 (GS) or cisplatin (GC) in ABTC. Herein, we report the results of a single arm phase II of modified GS in Taiwanese ABTC patients, NCT02425137. Methods: Patients with chemonaïve ABTC were eligible to receive 800mg/m2 gemcitabine with 10 mg/m2/min infusion, on day 1 plus daily 80/100/120 mg of S-1 (based on BSA) days 1-10, in a 2-week cycle. With Optimal Simon’s two-stage design and (p0= 0.4, p1= 0.6) for 12-week disease control rate (proportion of patients with complete or partial response [CR/PR] or stable disease ≥ 12 weeks [SD≥ 12weeks]) and given error probabilities (alpha = 0.05, beta = 0.2), the null hypothesis (p0) would be rejected if 24 or more patients with CR/PR/SD≥ 12weeks were observed among 46 accruals. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. Results: Between May 2015 and April 2016, totally 46 evaluable patients were enrolled to receive a median of 9.5 cycles (range: 3-31) of modified GS. After a median of 8.7 months (95% CI, 6.7-9.1) follow-up, 10 (21.7%) patients achieved PR and additional 23 (50%) had SD>12weeks. The median progression-free survival and overall survival was 5.6 (95% CI, 4.4-7.2) and 10.8 (95% CI, 7.6-not reached) months, respectively. All grade 3 treatment-related AEs were < 5%. The dose intensity of S-1 and gemcitabine were both more than 95%. Conclusions: By the observation of 33 patients with PR/SD≥ 12weeks, the null hypothesis was rejected. Modified GS is an active regimen with excellent safety profiles and deserves further investigation for the management of Asian ABTC patients. Clinical trial information: NCT 02425137.

Randomized phase III study of gemcitabine plus S-1 combination therapy versus gemcitabine plus cisplatin combination therapy in advanced biliary tract cancer: A Japan Clinical Oncology Group study (JCOG1113, FUGA-BT).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 205-205 ◽  
Author(s):  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Junki Mizusawa ◽  
Hiroshi Katayama ◽  
Makoto Ueno ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Standard Of Care ◽  
Phase Iii ◽  
Appetite Loss ◽  
Eligibility Criteria ◽  
Good Tolerability ◽  
Tract Cancer ◽  
Phase Iii Study

205 Background: Gemcitabine (GEM) plus cisplatin (GC) is the standard of care for advanced biliary tract cancer (BTC). However, GC is considered to be toxic because of nausea, vomiting, and appetite loss, and inconvenient due to requiring hydration before and after administration. GEM plus S-1 (GS) was reported to be promising with preferable efficacy and acceptable toxicity profile (UMIN000001685). This phase III study aimed to confirm the non-inferiority of GS to GC in terms of overall survival (OS). Methods: Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable biliary tract adenocarcinoma (gallbladder, intrahepatic biliary tract, extrahepatic biliary tract, or ampulla of Vater), an ECOG-PS of 0–1, and adequate organ function. In the GC arm, 1 g/m2 of GEM and 25 mg/m2 of cisplatin was infused on days 1 and 8 of a 21-day cycle. In the GS arm, 1 g/m2 of GEM was infused on days 1 and 8, and S-1 60, 80, or 100 mg/day according to body-surface area was administered from days 1 to 14 of a 21-day cycle. The primary endpoint was OS and the secondary endpoints included progression-free survival (PFS), response rate (RR), adverse events (AEs), clinically relevant AEs defined as any of grade 2 or more fatigue, appetite loss, nausea, vomiting, oral mucositis, and diarrhea. The sample size was calculated to be 350 with a one-sided alpha of 5%, a power of 80%, non-inferiority margin of 1.155 in terms of hazard ratio (HR). Results: From May 2013 to March 2016, 354 patients were enrolled. The non-inferiority of GS to GC was demonstrated (median OS: 13.4 months (m) in GC and 15.1 m in GS, HR 0.95; 90% confidence interval (CI), 0.78 to 1.15; P = 0.046 for non-inferiority). Median PFS was 5.8 m in GC and 6.8 m in GS (HR 0.86, 95% CI, 0.70-1.07). RR was 32.4% in GC and 29.8% in GS. Preliminary AEs data demonstrated that both treatments were generally well tolerated, although clinically relevant AEs were observed 34.7% in GC and 31.2 % in GS. Conclusions: GS demonstrated non-inferiority to GC in OS with good tolerability and was considered as new convenient option of standard of care without hydration for advanced BTC. Clinical trial information: UMIN000010667.

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