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.

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.

A phase II trial of oral S-1 combined with gemcitabine in patients with unresectable biliary tract cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15527-e15527 ◽  
Author(s):  
K. Nakamura ◽  
T. Yamaguchi ◽  
K. Sudo ◽  
T. Hara ◽  
T. Denda ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Bile Ducts ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Median Number ◽  
High Response Rate ◽  
Eligibility Criteria ◽  
Tract Cancer

e15527 Background: Optimal chemotherapy for unresectable biliary tract cancer is yet to be defined. We have conducted the phase II trial of Gemcitabine (GEM) with S-1, oral fluorouracil prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate to evaluate the activity and toxicity of such combination in patients with unresectable biliary tract cancer. Methods: Eligibility criteria were pathologically-proven biliary tract cancer, appropriate performance status 0 to 2, age 20 to 79 years, adequate hematological, renal and liver functions, no prior chemotherapy, and written informed consent. S-1 was given orally (30mg/m2) bid for 14 consecutive days and GEM (1000mg/m2) was given on day 8 and 15. Cycle was repeated every 21 days. Results: 30 patients with unresectable biliary tract cancer (Gall-bladder: intrahepatic bile ducts: extrahepatic bile ducts=7:16:7) were enrolled from March 2007 to December 2008. Patients characteristics were: median age; 67 (46–79), male/female; 20/10, PS 0/1/2; 16/13/1. Median number of cycles was 8 (range 1 to 14). Out of total 26 evaluable patients, objective responses were observed in 9 patients (30%); 16 patients achieved stable disease and 1 patients showed disease progression. Median survival was 390 days (95% c.i.: 290 - 490 days). The grade 3–4 toxicities observed were leucopenia (20%), neutropenia (40%), anemia (17%), thrombocytopenia (37%), anorexia (7%), fever (10%), rash (7%) and interstitial pneumonia (7%). Conclusions: The combination chemotherapy with GEM and S-1 was well tolerated and high response rate has been observed. This result is very promising but survival benefit against GEM monotherapy should be demonstrated in future phase 3 studies. No significant financial relationships to disclose.

Preliminary results of a multicenter phase II study of imatinib and fluorourcail/leucovorin (FU/LV) in patients with unresectable or metastatic gallbladder or biliary tract cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15502-e15502
Author(s):  
K. Sprenger ◽  
M. Moehler ◽  
E. Kettner ◽  
S. El-Batran ◽  
S. Hegewisch-Becker ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Response Assessment ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Multicenter Phase ◽  
Large Patient

e15502 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status < 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease. [Table: see text]

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.

Preliminary results of a multicenter phase II study of imatinib and fluorourcail/leucovorin (FU/LV) in patients with unresectable or metastatic gallbladder or biliary tract cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15622-e15622
Author(s):  
K. Schuette ◽  
M. Moehler ◽  
E. Kettner ◽  
S. Al-Batran ◽  
S. Hegewisch-Becker ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Response Assessment ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Multicenter Phase ◽  
Large Patient

e15622 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status < 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease. [Table: see text]

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.

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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