scholarly journals Adjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials

2020 ◽  
Vol 50 (12) ◽  
pp. 1353-1363 ◽  
Author(s):  
Satoshi Nara ◽  
Minoru Esaki ◽  
Daisuke Ban ◽  
Takeshi Takamoto ◽  
Kazuaki Shimada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Bile Duct ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tract Cancer ◽  
Adjuvant And Neoadjuvant Therapy ◽  
Duct Cancer

Abstract Cancer originating in the biliary tract can be classified as bile duct cancer (cholangiocarcinoma), gallbladder cancer, or ampullary cancer. Bile duct cancer is further divided to intrahepatic, perihilar and distal bile duct subtypes according to the anatomical location of the tumor. The biological characteristics of each tumor are heterogeneous. However, because of the rarity of each disease, the efficacy of new drugs has been tested in groups of patients with different biliary tract cancers. In patients with metastatic or recurrent biliary tract cancer, recent randomized clinical trials revealed the non-inferiority of gemcitabine + S-1 and the superiority of gemcitabine + cisplatin + S-1 compared with gemcitabine + cisplatin in terms of overall survival, thereby establishing a new standard treatment. In the field of adjuvant therapy for biliary tract cancer, the British BILCAP (capecitabine compared with observation in resected biliary tract cancer) study revealed longer median overall survival in the capecitabine group than in the observation group in the per-protocol analysis (but not in the intention-to-treat analysis), bringing a shift toward postoperative management. Several other studies of adjuvant therapy are ongoing, and they may lead to reforms in treatment strategy for resectable biliary tract cancer in the future. The use of neoadjuvant therapy for biliary tract cancer is in its infancy, but it is expected to overcome the limitations of adjuvant therapy for this malignancy. In this review, we summarized the evidence available from clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and described ongoing clinical trials.

Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer.

2021 ◽  
Author(s):  
Satoshi Nara ◽  
Minoru Esaki ◽  
Daisuke Ban ◽  
Takeshi Takamoto ◽  
Takahiro Mizui ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tract Cancer ◽  
Adjuvant And Neoadjuvant Therapy

Analysis of 94 patients with advanced biliary tract cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15172-15172
Author(s):  
B. Andritzky ◽  
S. Adler ◽  
I. Burkholder ◽  
I. Thöm ◽  
G. Schuch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bile Duct ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Primary Tumor ◽  
Median Overall Survival ◽  
Response Rate ◽  
Cytotoxic Agents ◽  
Tract Cancer ◽  
Line Chemotherapy

15172 Background: Cholangiocarcinoma or gallbladder cancer are often diagnosed at an advanced stage with limited treatment options. Methods: Between 1994 and 2004, 94 patients (pts) (47 male, 47 female) with advanced biliary tract cancer were treated at the Department of Oncology and Hematology, University Hospital Hamburg-Eppendorf. Clinical and histopathological characteristics, response to chemotherapy, and survival were investigated in a retrospective analysis. Median age was 59 years (range 30–80) and median Karnofsky performance status was 90%. Predominant histologic type was adenocarcinoma (94.7%). Primary tumor sites were extrahepatic bile duct (29.9%), gallbladder (28.7%), intrahepatic bile duct (10.6%), ampulla of Vater (2.1%), not specified (28.7%). Predominant localizations of metastases were liver (73 pts (77.7%)), lymph nodes (49 pts (52.1%)) and the peritoneum (14 pts (14.9%)). 33 pts (35.1%) underwent surgery of the primary tumor at time of diagnosis. Results: 72 of 94 pts (76.6%) received a first-line chemotherapy, all together 10 different chemotherapy regimens were used. The median number of cycles was 2.5 (range 1 - 12). A single agent chemotherapy with gemcitabine was the most often adminstered regimen (23 pts (31.9%)), followed by carboplatin and etoposide plus whole body hyperthermia (12 pts (16.7%)) and 5- fluorouracil and folic acid (10 pts (13.9%)). The overall response rate was 8.3% (95% CI 3.1 - 17.3) (34.7% SD, 47.2% PD, 9.7% not evaluable). Second-line chemotherapy was given in 27 patients, which induced no tumor response, but a stable disease rate of 22.2%. Median time to follow- up was 44.8 months. Survival was calculated for all 94 pts since time of diagnosis. Median overall survival was 12.2 months and median progression-free survival 9.2 months. The median overall survival time for the 72 pts who were treated with chemotherapy was 14.0 months, and for the 22 pts who did not receive chemotherapy 10.7 months (p=0.2). Conclusions: Our analysis showed a poor prognosis for patients with advanced biliary tract cancer. Response rate to chemotherapy was low. Therefore, well tolerated cytotoxic agents should be used and new treatment strategies (including molecular targeted therapy) should be further investigated. No significant financial relationships to disclose.

scholarly journals Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer

2019 ◽  
Vol 29 (5) ◽  
pp. 180-186 ◽  
Author(s):  
Takeshi Makiuchi ◽  
Tomotaka Sobue ◽  
Tetsuhisa Kitamura ◽  
Norie Sawada ◽  
Motoki Iwasaki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Alcohol Consumption ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Bile Duct Cancer ◽  
Intrahepatic Bile Duct ◽  
Tract Cancer ◽  
Duct Cancer

Neutrophil/lymphocyte ratio (NLR) may predict prognostic factor with gemcitabine, cisplatin (GC) for patients with advanced biliary tract cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 410-410
Author(s):  
Toru Otsuru ◽  
Daisuke Sakai ◽  
Akie Kimura ◽  
Chiaki Inagaki ◽  
Naohiro Nishida ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Bile Duct ◽  
Prognostic Factor ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Intrahepatic Bile Duct ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Tract Cancer

410 Background: There is little information available about prognostic markers of GC (gemcitabine, cisplatin) in patients with advanced biliary tract cancer (BTC). Neutrophil/lymphocyte ratio (NLR) in several cancers was might to be a prognostic factor associated with clinical outcomes, we examine NLR in patient with BTC underwent chemotherapy (GC). Methods: Retrospective chart review for consecutive patients who underwent GC for advanced BTC in our institute were performed. The patients who were enrolled in ongoing clinical trials were excluded. Gemcitabine and cisplatin were administered intravenously at doses of 1,000 or 25 mg/m2, on day one and eight, every three weeks. We divided these patients based on estimated NLR, and evaluated the clinicopathological factors and survival in the two groups (NLR ≥ 3 or < 3). Results: 57 patients from 2013 to 2017 were reviewed. 23 patients were in NLR ≥ 3 group and 34 patients were in NLR < 3 group. Patients characteristics were as follows; median age, 68 years old (range: 38-83) years: male 36 (63%); primary tumor lesion, intrahepatic bile duct 6 (10%)/extrahepatic bile duct 32 (56%)/gallbladder 18 (32%)/ampulla of vater 1 (2%); therapeutic purpose, palliative 50 (88%)/adjuvant 5 (8%)/neoadjuvant 2 (4%); PS, 0/1. Response rate of the patients who had measurable lesion according to RECIST v1.1 was 17% (8/46), and disease control rate was 70% (32/46). The progression-free survival rate between the two groups is not significantly different. Although, the median overall survival (OS) of NLR ≥ 3 group was 11.8 months, while OS of NLR < 3 group was 29.2 months. The overall survival rate in the NLR ≥ 3 group was significantly lower than that in the NLR < 3 group ( P = 0.0339). Conclusions: Our study confirmed that high NLR is associated with worse OS and PFS, and suggested it may be a predictive marker for GC chemotherapy in patients with BTC.

Second-line chemotherapy in patients with advanced biliary tract cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 429-429 ◽  
Author(s):  
Naminatsu Takahara ◽  
Yousuke Nakai ◽  
Hiroyuki Isayama ◽  
Takashi Sasaki ◽  
Kazunaga Ishigaki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Bile Duct ◽  
Biliary Tract Cancer ◽  
Tumor Response ◽  
Response Rate ◽  
Second Line ◽  
Tract Cancer ◽  
Duct Cancer ◽  
Line Chemotherapy

429 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is a palliative chemotherapy. Although the survival benefit of first-line chemotherapy (CT1) including gemcitabine and cisplatin (GC) had been established in prospective randomized trials, the safety and efficacy of second-line chemotherapy (CT2) have yet to be elucidated. Methods: Consecutive advanced BTC patients receiving CT1 followed by CT2 between 2000 and 2016 were enrolled. We investigated factors associated with receiving CT2, treatment outcomes of CT2, and the prognostic factors for overall survival (OS) with CT2 to determine which patients could be expected to benefit from CT2. Results: Among 309 advanced BTC patients receiving CT1, including those with 108 intrahepatic bile duct cancer, 96 gallbladder cancer, 88 extrahepatic bile duct cancer and 17 papilla cancer, CT2 was given in 139 patients (45%). Compared to patients without CT2, younger patients (median; 67 vs. 70 years, p < 0.01) and patients with better PS (PS 0-1; 98% vs. 94%, p = 0.06), and those who achieved higher tumor response by CT1 (response rate; 19% vs. 7%, p < 0.01) had higher chance to receive CT2. Objective response rate and disease control rate of CT2 were 4% and 50%, respectively. Median progression-free survival (PFS) and overall survival (OS) from the beginning of CT2 were 2.8 and 7.7 months, respectively. Prognostic factors impacting OS with CT2 were PS (0 vs. 1-2, hazard ratio [HR] 1.28, p=0.05), tumor response to CT1 (PR-SD vs. PD, HR 1.62, p = 0.02), and CEA (<5.0 vs. ≥5.0 IU/mL, HR 1.52, p = 0.03). Conclusions: Although the efficacy of CT2 was modest at present, it may deserve to be considered in patients who maintained systemic condition in clinical practice. Further investigations are necessary both to to develop more effective regimens and to select patient who will benefit from CT2 in order to maximize the efficacy and to avoid unnecessary toxicity and expense.

A randomized phase III trial comparing adjuvant chemotherapy with S-1 vs. surgery alone in patients with resectable biliary tract cancer (JCOG1202: ASCOT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4144-TPS4144 ◽  
Author(s):  
Masafumi Ikeda ◽  
Kohei Nakachi ◽  
Masaru Konishi ◽  
Shuichi Mitsunaga ◽  
Junki Mizusawa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bile Duct ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Residual Disease ◽  
Extrahepatic Bile Duct ◽  
Intrahepatic Bile Duct ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Tract Cancer

TPS4144 Background: No standard adjuvant treatment has been established for patients with curatively resected biliary tract cancer (BTC). S-1, which is one of the oral fluoropyrimidine derivatives, showed promising efficacy with a mild toxicity profiles in patients with advanced BTC, and the survival benefit of adjuvant S-1 therapy has been demonstrated in patients with resected gastric cancer and pancreatic cancer. The aim of this open-label, multicenter, randomized phase III trial is to assess whether adjuvant S-1 would prolong the overall survival in patients with resected BTC. Methods: The main eligibility criteria are as follows: 1) curatively resected carcinoma of the extrahepatic bile duct, gallbladder or ampulla of Vater (T2-4, N0, M0 or T1-4, N1, M0), or carcinoma of the intrahepatic bile duct (T1-4, N0-1, M0) (7th UICC classification), 2) histologically confirmed adeno (squamous) carcinoma, 3) R0 or R1 residual disease, 4) age 20 to 80 years, 5) ECOG performance status 0 or 1, 6) no prior chemotherapy or radiotherapy, 7) adequate organ functions, 8) written informed consent. Patients are randomly assigned to the surgery alone arm (arm A) or the adjuvant S-1 arm (arm B) by the minimization method for balancing institution, primary site of cancer and lymph node metastasis between the arms. Patients in arm A do not receive any anti-cancer treatment, while patients in arm B receive 4 cycles of oral S-1 chemotherapy at the dose of 40 mg/m2 twice daily for 4 weeks followed by 2 weeks of rest. The primary endpoint is overall survival, while the secondary endpoints are relapse-free survival, incidence of (serious) adverse events, and proportion of treatment completion. We assumed a 3-year survival in arm A of 47% and a 10% increase in the 3-year survival in arm B. The sample size was calculated as a total of 350, with a one-side alpha of 5% and power of 70%; planned accrual period is 4 years, and follow-up period, 3 years. Primary analysis will be conducted at 3 years and updated analysis will be conducted at 5 years after closing of accrual. As of Jan 31, 2016, a total of 285 patients have already been enrolled in this trial from Sep 2013. Clinical trial information: UMIN000011688.

Correlation between overall survival and other efficacy endpoints in advanced biliary tract cancer: Literature-based analysis from 13 randomized trials of first-line chemotherapy.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 352-352
Author(s):  
Toshikazu Moriwaki ◽  
Shinji Endo ◽  
Yoshiyuki Yamamoto ◽  
Takeshi Yamada ◽  
Akinori Sugaya ◽  
...  
Keyword(s):  
Overall Survival ◽  
Correlation Coefficient ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Randomized Trials ◽  
First Line ◽  
Biliary Tract Neoplasms ◽  
Tract Cancer ◽  
The Impact ◽  
Line Chemotherapy

352 Background: Chemotherapy for advanced biliary tract cancer (ABC) has progressed. Now gemcitabine plus cisplatin combination is considered the standard 1st-line treatment based on the results of many randomized studies. However, the impact of various efficacy parameters on overall survival (OS) remains unclear. Methods: We searched PubMed database with the key words of (“biliary tract neoplasms” or “bile duct neoplasms” or “gallbladder neoplasms” or “cholangiocarcinoma” [All fields]) AND (“chemotherapy”[All fields]) AND Clinical trial [ptyp] between Apr 1984 to Jun 2013 and abstracts presented at the meetings of ASCO/Gastrointestinal Cancers Symposium (2004–2013) and ESMO/WCGC (2002–2013). Then we identified randomized trials of 1st-line chemotherapy for ABC, and analyzed the relations between the results of OS and those of progression-free survival (PFS) or time to progression (TTP), response rate (RR), disease control rate (DCR), post-progression survival (PPS = median OS − median PFS/TTP), and the proportion of patients who received 2nd-line chemotherapy (%2nd). Results: Among 329 papers/abstracts retrieved, 13 randomized trials, 26 treatment arms of first-line chemotherapy for ABC were identified. Number of trials with information on median OS, median PFS/TTP, hazard ratio (HR) for OS and PFS/TTP, RR, DCR, and %2nd were 13, 13, 6, 13, 12, and 7, respectively. The analysis of all these trials demonstrated the median values (range) of OS, PFS/TTP, HR of OS, HR of PFS/TTP, RR, DCR, PPS, and %2nd were 9.4 (4.6–13) months, 5.3 (2.7–8.5) months, 0.71 (0.39–0.93), 0.65 (0.44–0.85), 20 (7.1–36) %, 67 (21–87) %, 4.0 (1.0–7.6) months, and 41 (15–79) %, respectively. Spearman rank correlation coefficient of differences (Δ) OS with ΔPFS/TTP, ΔRR, ΔDCR, and ΔPPS were 0.66, − 0.07, 0.66, and 0.34, respectively. The correlation coefficient between HRs for PFS/TTP and OS was 0.60. The correlation coefficient between ΔPPS and Δ%2nd was − 0.15. Conclusions: OS was moderately associated with PFS/TTP and DCR.

Influence of obstructive jaundice on chemotherapy in patients with unresectable biliary tract cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 336-336
Author(s):  
Satoshi Shimizu ◽  
Shuichi Mitsunaga ◽  
Izumi Ohno ◽  
Hideaki Takahashi ◽  
Hiroyuki Okuyama ◽  
...  
Keyword(s):  
Overall Survival ◽  
Obstructive Jaundice ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Biliary Obstruction ◽  
Chief Complaint ◽  
Tract Cancer ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

336 Background: The aim of this study was to investigate the influences of obstructive jaundice (OJ) in unresectable biliary tract cancer (BTC) patients. Methods: Data of a total of 200 patients who were newly diagnosed as having unresectable BTC and received chemotherapy between July 2006 and December 2012 were retrospectively reviewed. Patients were divided into two groups according to whether or not they presented with OJ as the incipient chief complaint (Group 1, patients with OJ; Group 2, patients without OJ). Results: There were 81 patients in Group 1 and 119 patients in Group 2. In regard to the primary site (Group 1/Group 2), 29 had perihilar (27/2), 7 had distal (7/0), 68 had intrahepatic (15/53), 92 had gallbladder (31/61) and 4 had ampulla of vater (1/3) (p<0.01). The rate of distant metastasis was 60% in Group 1 and 76% in Group 2 (p=0.02). The performance status was good (0 or 1) in 96% of cases of both the groups. There were no significant differences in the median survival time between Group 1 and Group 2 (9.0 months vs. 9.0 months, p=0.42) or in the progression free survival of 1st line chemotherapy between the two groups (4.1 months vs. 3.7 months, p=0.08). The rate of development of biliary obstruction in Group 1 was significantly high during the first line chemotherapy (56% vs. 10%, p<0.01). Discontinuation of 1st line chemotherapy was necessitated due to biliary obstruction in 9 patients (10%) of Group 1 and none of the patients (0%) of Group 2. Multivariate analysis showed that absence of metastasis and use of a doublet chemotherapy regimen were significantly correlated with the overall survival, but not the presence of OJ as the incipient chief complaint (HR, 0.772; 95% CI, 0.532-1.119). Conclusions: Patients with OJ as the incipient chief complaint showed high rate of recurrent biliary obstruction and discontinuation chemotherapy due to biliary obstruction. However, OJ may not disadvantage for overall survival in BTC.

scholarly journals Neither Neoadjuvant nor Adjuvant Therapy Increases Survival After Biliary Tract Cancer Resection with Wide Negative Margins

2012 ◽  
Vol 16 (9) ◽  
pp. 1666-1671 ◽  
Author(s):  
Evan S. Glazer ◽  
Ping Liu ◽  
Eddie K. Abdalla ◽  
Jean-Nicolas Vauthey ◽  
Steven A. Curley
Keyword(s):  
Adjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cancer Resection ◽  
Tract Cancer
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