Chemotherapy For Biliary Tract Cancer Research Articles

Phase II study of fixed dose-rate gemcitabine plus S-1 as second-line treatment in advanced biliary tract cancer.

301 Background: Cisplatin plus gemcitabine (GC) is considered as standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). However, no standard therapy is established for second-line setting. Some clinical studies showed that gemcitabine was more effective if administered by the fixed dose rate method, and S-1 had anti-tumor effect as second-line chemotherapy for BTC. We evaluated the efficacy and safety of combination therapy of fixed dose-rate gemcitabine and S-1 after failure of GC or gemcitabine alone. Methods: This study was a single arm phase II study, and primary endpoint was response rate (RR) with MinMax two stage design to test the hypothesis that RR was more than 7%. Number of patients needed was 35 with a power of 90% and two-sided α value of 0.05. Patients received gemcitabine (1,000 mg/m2, div, over 100 minutes, day 1) and S-1 (40 mg/m2 twice daily, oral, day 1-7), every two weeks until disease progression or intolerable adverse events. Results: Forty patients were enrolled from July, 2011 to Nov., 2014. Of 23 patients in the first stage, two patients showed response and proceeded to the second stage. Overall response rate was 7.5%. Overall survival, progression-free survival and disease control rate were 7.7 months, 2.6 months, and 47.5%, respectively. Common adverse events were anemia (97.2%), thrombocytopenia (66.7%), leukopenia (47.2%), neutropenia (41.7%), anorexia (39.0%) and fatigue (37.8%). Grade 3–4 adverse events were leukopenia (19.5%), neutropenia (19.5%), anemia (14.6%), thrombocytopenia (7.3%) and anorexia (4.8%). Biliary tract infection led to death in two patients; however, these were reported as not related to this study treatment. Conclusions: Fixed dose-rate gemcitabine plus S-1 was tolerable as second-line settings in BTC; however, its activity was modest for patients refractory to the standard gemcitabine. Clinical trial information: UMIN000005918 Clinical trial information: UMIN000005918.

P1310 : Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1) – a randomized, multidisciplinary, multinational phase III trial

Despite complete resection, disease-free survival (DFS) of patients with cholangiocarcinoma (CCA) is less than 65 % after one year and not more than 35 % after three years. For muscle invasive gallbladder carcinoma (GBCA), prognosis is even worse, with an overall survival (OS) of only 30 % after three years. Thus, evaluation of adjuvant chemotherapy in biliary tract cancer in a large randomized trial is warranted. Methods/Design ACTICCA-1 is a randomized, multidisciplinary, multinational phase III investigator initiated trial. With respect to data obtained in the ABC-02 trial, we selected the combination of gemcitabine and cisplatin for 24 weeks as investigational treatment. Based on adjuvant trials in pancreatic cancer with comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of chemotherapy was stipulated. Due to the different prognosis and treatment susceptibility of muscle invasive carcinoma, two separate cohorts (CCA and GBCA) were included to capture the potentially different treatment effects. Randomization is stratified for lymph node status for both cohorts and localization for CCA. The primary endpoint is DFS and secondary endpoints include OS, safety and tolerability of chemotherapy, quality of life, and patterns of disease recurrence. For CCA, adjuvant chemotherapy should increase DFS 24 months post-surgery from 40 to 55 % to be considered relevant. With a power of 80 % and a significance level of 5 %, 271 evaluable study patients have to be followed for 24–28 months to observe 166 events. For GBCA, chemotherapy should increase DFS 24 months post-surgery from 35 to 55 % to be of relevance; thus, 154 evaluable study patients have to be monitored for 24–28 months to observe 90 events. In both cohorts, randomization will be 1:1 with chemotherapy for 24 weeks and imaging every twelve weeks. In 2014, the study was initiated in Germany and in The Netherlands (funded by the Deutsche Krebshilfe, the Dutch Cancer Society, and supported by medac GmbH). Sites in Australia, Denmark, and the United Kingdom (funded by Cancer Research UK) are joining 2015. Trial registration The study is registered with ClinicalTrials.gov (NCT02170090) and the European Clinical Trials Database (2012-005078-70). Registration date is 06/18/2014.

Fluoropyrimidine-based adjuvant chemotherapy in patients with resected biliary tract cancers.

e15108 Background: The role of adjuvant therapy is controversial in patients with resected biliary tract cancers(BTC). There are few data regarding the benefit of adjuvant chemotherapy in BTC. Meth...

Current status and future direction of chemotherapy for biliary tract cancer

Current status and future direction of chemotherapy for biliary tract cancer

Patients with recurrent biliary tract cancer have a better prognosis than those with unresectable disease: retrospective analysis of a multi‐institutional experience with patients of advanced biliary tract cancer who received palliative chemotherapy

Prognostic factors for patients with advanced biliary tract cancer (BTC) who received palliative chemotherapy have not been fully established. Especially, the status of unresectable/recurrent disease has not been well studied because of a small number of patients with recurrent BTC in previous studies. This multicenter retrospective study was conducted in 18 institutions in Japan. We retrospectively reviewed data regarding 403 patients with pathologically proven BTC who received palliative chemotherapy between April 2006 and March 2009. One hundred and ninety-two patients with recurrent BTC were included. Univariate and multivariate analyses were performed to identify prognostic factors. The median overall survival was significantly longer in the recurrent BTC patients than in the unresectable BTC patients (398 days vs. 323 days, P = 0.004). After adjustment using multivariate analysis, the status of recurrent/unresectable disease remained an independent prognostic factor (hazard ratio 1.33, 95% confidence interval 1.04-1.70, P = 0.022) in addition to performance status, extent of disease, carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels. The status of unresectable/recurrent disease was shown as an independent prognostic factor in the BTC patients. This result may help to predict life expectancy of BTC patients and design future clinical trials evaluating palliative chemotherapy in BTC.

A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer

Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.

Abstract 2840: Dendritic cell-based immunotherapy targeting WT1 and MUC1 for advanced biliary tract cancer.

Abstract Objectives:Despite intensive chemotherapy for biliary tract cancer (BTC), the outcome is not enough. Dendritic cells are the powerful antigen-presenting cells that have attracted attention from the efficacy of DC-based immunotherapy against many types of cancers. The objective of this study was to clarify the safety and efficacy of dendritic cell therapy for BTC.Methods: This retrospective study selected patients who underwent DC-based vaccine for BTC between May of 2009 and February of 2012. The safety of this treatment, median survival time (MST), 1-year survival rate, objective response rate (ORR), and disease control rate (DCR) were evaluated. The univariate and multivariate analyses were performed to identify the efficacy of DC by a Cox proportional hazards analysis.Results:Twenty-seven patients were selected for the study. The patients, and all but one patient had previous therapy, 13 patients had undergone prior surgical resection, and 21 patients went on to receive chemotherapy. No serious treatment-related adverse events were observed during the study period. One-year survival rate from 1st vaccination was 22 % and from the initial diagnosis was 67%. The MST from 1st vaccination and from the initial diagnosis were 8.2 months and 18.5 months, respectively. DCR and ORR were 37% and 11%,respectively. None of 27 patients showed complete response (CR), but we have found out 3 cases of partial responses (PR) and 7 cases of stable disease (SD).Furthermore, LDH, CRP, DTH, Performance Status (PS), combination with lymphokine-activated killer, chemotherapy were found to be statistically significant independent risk factors in multivariate analysis.Conclusion: DC-based immunotherapy for BTC was safe and prolonged the MST of the patients with BTC compared to chemotherapy alone,comparing the result from UK ABC-02 trial. DC-based immunotherapy for BTC may another option for BTC patient who has no chance for curative surgery. Citation Format: Masanori Kobayashi, Tomoyo Sakabe, Mitsugu Tanii, Hirofumi Abe, Hedenori Takahashi, Shun-ichi Tsujitani, Shigetaka Shimodaira, Yoshikazu Yonemitsu, Masato Okamoto, Masaki Nagaya. Dendritic cell-based immunotherapy targeting WT1 and MUC1 for advanced biliary tract cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2840. doi:10.1158/1538-7445.AM2013-2840

Abstract 2081: Evaluation of Src as a therapeutic target in biliary tract cancer using bosutinib, a c-Src/Abl kinase inhibitor.

Abstract Background: Src is a nonreceptor tyrosine kinase involved in the crosstalk and mediation of many signaling pathways that promote cell proliferation, invasion and angiogenesis. Elevation of Src activity has been reported in many types of cancers including biliary tract cancer (BTC). In BTC, no molecular therapeutic target has been validated so far. Therefore, the prognosis of advanced BTC is limited and there is a huge unmet medical need in this area. The purpose of this study is to evaluate of Src as a therapeutic target in BTC and to elucidate the therapeutic potential and action mechanism of bosutinib, an orally active small molecule c-Src/Abl kinase inhibitor, alone or in combination with chemotherapy for the treatment of BTC. Methods: Experiments were conducted using 8 human biliary tract cancer cell lines (SNU-245, 308, 478, 869, 1079, 1196, HuCCT1, TFK1). MTT assay, colony formation assay and 3D culture were done for determining growth inhibitory effect of bosutinib, alone or in combination with chemotherapeutic agents (gemcitabine, cisplatin). Cell cycle distribution was analyzed by FACS Calibur flow cytometer. Matrigel invasion assay and wound healing assay were done. The methods described by Chou and Talalay were used to determine whether a synergistic effect existed between drug combination. Results: pSrc was highly expressed in most BTC cells. Bosutinib inhibited the growth of BTC cells, especially SNU308, SNU478 and HuCCT1 (IC50, 0.6-0.8 μmol/L). Bosutinib induced G1 arrest (decrease of cyclin D, cyclin E, cyclin A, cyclin B and increase of p27) in SNU308 and SNU478. It decreased pSrc, pFAK, pAKT and pERK in these cells. Bosutinib also inhibited the cell migration and invasion in parallel with decrease of snail, not only in SNU308, SNU478 cells but also in several other cells. Interestingly, bosutinib showed synergistic antiproliferative effects (Combination Index value &amp;lt;1) with gemcitabine in 4 out of 8 BTC cells. Bosutinib was downregulated TS (thymidine synthase) expression, one of resistance mechanisms to gemcitabine. Bosutinib also showed synergistic anti-invasion activity in combination of gemcitabine or cisplatin. Conclusion: Taken together, these preclinical evaluations reveal that Src could be a potential therapeutic target in biliary tract cancer and support clinical development of bosutinib alone or in combination with chemotherapy in biliary tract cancer. Citation Format: Ah-Rong Nam, Ahrum Min, Sae-Won Han, Sang-hyun Song, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Youg-Jue Bang. Evaluation of Src as a therapeutic target in biliary tract cancer using bosutinib, a c-Src/Abl kinase inhibitor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2081. doi:10.1158/1538-7445.AM2013-2081

Chemotherapy for biliary tract cancer

Chemotherapy for biliary tract cancer

Outcome of Infusional 5-Fluorouracil, Doxorubicin, and Mitomycin-C (iFAM) Chemotherapy and Analysis of Prognostic Factors in Patients with Refractory Advanced Biliary Tract Cancer

Objective: The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) as salvage chemotherapy in biliary tract cancer (BTC) and to identify prognostic factors. Methods: Fifty patients received 5-FU 800 mg/m² over 10 h on days 1–5, doxorubicin 30 mg/m² on day 1 and mitomycin-C 8 mg/m² on day 1, every 4 weeks. The primary endpoint was the overall survival (OS) rate at 6 months. Results: The responses to iFAM were as follows: partial response in 2 patients (4.2%) and stable disease in 9 patients (18.7%). The median progression-free survival and OS were 2.2 months and 5.6 months, respectively. The 6-month OS rate was 48%. Grade 3/4 adverse events included neutropenia (10%), thrombocytopenia (8%), and anemia (2%). Based on multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status, serum albumin, and response to previous chemotherapy were significantly associated with OS. Three risk groups based on the number of 3 poor prognostic factors (0 vs. 1 vs. 2–3) were well correlated to OS (8.7 vs. 5.5 vs. 2.4 months, respectively; p = 0.0002). Conclusions: iFAM as salvage regimen has modest effect and tolerable toxicity in advanced BTC. The described risk group classification may help guide treatment plans.

Photodynamic therapy with temoporfin in combination with gemcitabine/capecitabine in biliary tract cancer: Feasibility and safety in a randomized phase II trial.

e14637 Background: Patients whocannot be offered curative surgical treatment for biliary tract cancer (BTC) have a poor prognosis. Photodynamic therapy (PDT) has been shown to improve survival and quality of life in patients with unresectable BTC. A combination of treatment modalities might improve survival further, but such data are still lacking. Therefore we have performed the first randomized trial on the combination of temoporfin/PDT and chemotherapy. Here we report data on the feasibility and safety. Methods: Randomized phase II trial, planned to include 20 patients with time to progression as primary endpoint, feasibility and toxicity as secondary endpoints. Inclusion criteria were unresectable BTC confirmed by histology or cytology, need for biliary stent, bilirubin level &lt; 50 mmol/L and no previous cancer disease. The treatment arms were: A: Stent, temoporfin / PDT followed by gemcitabin / capecitabin (GemCap). B: Stent, GemCap. Only one initial PDT treatment was given. Results: Twenty patients with locally advanced and metastatic disease were included, 10 patients in each arm. Two patients in arm B did not receive any treatment (thrombocytopenia, study withdrawal) and two patients in arm A did not receive chemotherapy (ECOG&gt;2, infection). PDT was feasible in all 10 patients without any acute procedure-related complication. During the first 30 days, two cases of cholangitis in arm A and three in arm B were observed. Cutaneous erythema (grade 1-2) was observed after PDT in two patients. Conclusions: PDT using temoporfin in combination with chemotherapy in BTC was feasible. Restrictions to light exposure were well tolerated. PDT in combination with chemotherapy did not increase the complication rate during the first 30 days follow-up. Three months follow-up data will be available at the time for presentation. Larger prospective trials are warranted to assess the efficacy of this treatment combination.

Role of chemotherapy in treatments for biliary tract cancer

The purpose of chemotherapy in patients with advanced solid cancers, including biliary tract cancer, is generally to improve the survival and quality of life of the patients. Also, adjuvant chemotherapy is expected to increase the curability of surgery in patients scheduled to undergo surgery. Most patients with unresectable biliary tract cancer develop obstructive jaundice, and biliary drainage is needed before any of the aforementioned treatments. Once jaundice is resolved by stenting of the bile duct or bilio-intestinal bypass, cholangitis often develops, leading to rapid deterioration of the patient's general condition. Therefore, the beneficial effect of chemotherapy in such patients remains controversial. A few randomized controlled trials have demonstrated the survival benefit of chemotherapy as compared with supportive care. In one of these trials, improvement of the quality of life was also confirmed. Recently, since the survival benefit of combined gemcitabine plus cisplatin therapy over gemcitabine alone has been demonstrated in randomized controlled clinical trials, this combined regimen has been recognized as a standard therapy for unresectable biliary tract cancer. A second-line regimen is now expected to be established for patients with gemcitabine-refractory biliary tract cancer, although the significance of second-line therapy remains unclear. One of the next issues in relation to chemotherapy for biliary tract cancer is the development of molecular-targeted agents; however, few large clinical trials of such agents have been conducted for biliary tract cancer. Various issues in chemotherapy for biliary tract cancer remain to be investigated, and global cooperation is necessary to conduct large clinical trials.

Adjuvant chemotherapy for resectable biliary tract cancer: current status and future direction

The prognosis of patients with biliary tract cancer remains unsatisfactory even with surgery owing to the high recurrence rate. Therefore, an effective adjuvant chemotherapy is required to prolong survival. A few randomized controlled trials in patients with limited biliary tract cancer have been reported, but the efficacy of adjuvant chemotherapy could not be clarified. To date, effective adjuvant chemotherapy with evidence has not been established, and the standard therapy for patients with resectable biliary tract cancer has only been surgical treatment. Recently, a number of newer toxic agents have been shown to induce response in patients with advanced biliary tract cancer. Moreover, the morbi-mortality rate of operation for this cancer has been decreasing owing to advances in operative techniques and perioperative management. Given this background, a number of adjuvant chemotherapy trials have been started using gemcitabine, capecitabine, S-1, and combination chemotherapy with platinum. The results of these trials will be reported in the near future. Overall, the important aspects of adjuvant chemotherapy for biliary tract cancer are to establish well-organized and active clinical trial study groups, to conduct well-designed multicenter randomized controlled trials, and to continue such trials without interruption in the future.

Outcomes of continuously infused 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) as salvage regimen in patients with biliary tract cancer.

282 Background: In advanced biliary tract cancer, after failure of first-line chemotherapy, salvage chemotherapy has not yet been established and the prognostic factors in salvage setting have not been widely known. The purpose of this study was to evaluate the efficacy and safety of iFAM as salvage chemotherapy in biliary tract cancer and to reveal the prognostic factors. Methods: Eligibility included: 1) age 18-75, 2) histologically confirmed biliary tract cancer, 3) previously treated with palliative first-line chemotherapy, 4) ECOG PS 0-2, 5) adequate organ function. iFAM consisted of 5-FU 800 mg/m2 over 12 hour on days 1-5, doxorubicin 30 mg/m2 on day 1, and mitomycin-C 8 mg/m2 on day 1, every 4 weeks. Results: Between February 2003 and August 2009, 50 patients (pts) were enrolled. The median age was 57.3 yrs (range: 26.0-71.5 yrs), and there were 33 men (66%). 32 pts (64%) had ECOG PS 0-1 and 18 pts (36%) had PS 2. Biliary tract cancers were extrahepatic cholangiocarcinoma (30%), intrahepatic cholangiocarcinoma (30%) and gallbladder cancer (40%). Previous chemotherapy mainly consisted of gemcitabine-based and 5-FU-based regimens. Median cycles of iFAM were 2 (range: 1-6). Best responses to iFAM were PR in 2 (4%) pts and SD in 9 (18%), that is response rate was 4% and disease control rate was 22% (95% CI: 7.35-28.65). The median PFS and OS were 2.2 (95% CI: 2.0–2.4) months and 5.0 (95% CI: 3.3–6.7) months, respectively. Grade 3/4 hematologic toxicities were neutropenia (10%), anemia (2%), and thrombocytopenia (8%). Frequent nonhematologic toxicities were alopecia (34%), stomatitis (28%), vomiting (24%), and diarrhea (12%), which were grade 1/2. ECOG PS (0-1 vs 2) was significant prognostic factor for both PFS (p=0.029) and OS (p=0.025). Poor response to previous chemotherapy (p=0.031) were poor prognostic factors for OS. Conclusions: iFAM is an effective and safe treatment option in refractory biliary tract cancer and can be considered as salvage regimen, especially for patients with good PS and good response to previous chemotherapy. No significant financial relationships to disclose.

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

Evaluation of: Valle J, Wasan H, Palmer DH et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N. Engl. J. Med. 362, 1273–1281 (2010).Biliary tract cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy has not been established yet. The evaluated article reports on the first Phase III randomized controlled multicenter trial (ABC-02 trial) on palliative chemotherapy for biliary tract cancer. A total of 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer or ampullary cancer were included to receive either cisplatin followed by gemcitabine or gemcitabine alone for up to 24 weeks. The primary end point was overall survival and the secondary end point was progression-free survival. The median overall survival was 11.7 months in the cisplatin plus gemcitabine group and 8.1 months in the gemcitabine only group. The median progression-free survival was 8.0 months in the cisplatin plus gemcitabine group and 5.0 months in the gemcitabine-only group (p < 0.001). Adverse events were comparable in the two groups. Cisplatin plus gemcitabine, compared with gemcitabine alone, was associated with a significant survival advantage without an increase in substantial toxicity.

Current status and further direction of Systemic chemotherapy for biliary tract cancer

Current status and further direction of Systemic chemotherapy for biliary tract cancer

Gemcitabine-based versusfluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study

BackgroundThere is no standard palliative chemotherapy regimen in biliary tract cancers (BTC). Fluoropyrimidine or gemcitabine, with or without platinum, are most frequently used. We conducted this study to clarify the efficacy of palliative chemotherapy in BTC.MethodsPatients with unresectable BTC treated with palliative chemotherapy between Oct 2001 and Aug 2006 at Seoul National University Hospital were reviewed retrospectively. Histologically confirmed cases of intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater carcinoma were enrolled. We analyzed the efficacy of regimens: gemcitabine (G) versus fluoropyrimidine (F) and with or without platinum (P).ResultsA total of 243 patients were enrolled. 159 patients (65%) were male and the median age of the patients was 60 years (range 26–81). Intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater carcinoma were 92, 72, 58, and 21 cases, respectively. The median progression free survival (PFS) was 4.3 months (95% CI, 3.7–4.9) and median overall survival (OS) was 8.7 months (95% CI, 7.4–10.0). Ninety-nine patients received G-based chemotherapy (94 GP, 5 G alone), and 144 patients received F-based chemotherapy (83 FP, 61 F alone). The response rate (RR), disease control rate (DCR), PFS and OS of G-based chemotherapy versus F-based chemotherapy were 16.7% vs. 19.5% (P = 0.591), 52.8% vs. 58.9% (P = 0.372), 4.0 months vs. 4.3 months (P = 0.816), and 7.8 months vs. 9.1 months (P = 0.848), respectively. Sixty-six patients received F or G without P, and 177 patients received F or G with P. The RR, DCR, PFS and OS of chemotherapy without P versus chemotherapy including P were 12.7% vs. 20.6% (P = 0.169), 46.0% vs. 60.6% (P = 0.049), 3.3 months vs. 4.4 months (P = 0.887), and 10.6 months vs. 8.1 months (P = 0.257), respectively.ConclusionIn unresectable BTC, F-based and G-based chemotherapy showed similar efficacy in terms of RR, DCR, PFS and OS. The benefit of adding P to F or G was not significant except for DCR. Further prospective studies which define the efficacy of various chemotherapeutic regimens in BTC are warranted.

Current status of systemic chemotherapy for biliary tract cancer

Current status of systemic chemotherapy for biliary tract cancer

Gemcitabine in combination with EGF-Receptor antibody (Cetuximab) as a treatment of cholangiocarcinoma: a case report

BackgroundExtensive disease of cholangiocarcinoma (CC) determines the overall outcome and limits curative resection. Despite chemotherapy, which has been introduced to improve the outcome of biliary tract malignancies, the benefit in survival is still marginal.Case presentationWe report a 69-year-old patient with non-resectable CC showing hepatic metastasis and peritoneal carcinomatosis. Diagnosis was based on computed tomography, mini-laparoscopy and bioptic specimens. Histology revealed an adenocarcinoma of the biliary tract with expression of epithelial growth factor receptor. After informed consent the patient received experimental gemcitabine (1000 mg/m2) every other week and cetuximab (250 mg/m2) weekly for palliative chemotherapy. During the reported follow up (since time of first presentation) 20 cycles of chemotherapy were administered. Relevant chemotherapy-related toxicity was limited on gemcitabine-associated side effects. Predominantly, haematological toxicity (CTC, grade 3) and neutropenic fever (CTC, grade 3) promoted by catheter-related sepsis were observed. Cetuximab caused only mild skin toxicity (CTC, grade 1).Chemotherapy led to a partial response (> 30% reduction, according to RECIST) of the target lesions and disappearance of the peritoneal carcinomatosis as shown by computed tomography. Partial response occurred after 17 weeks of treatment and remained stable during the entire course of chemotherapy for 9.7 months. In parallel, Ca 19-9 serum levels, which were elevated 5-fold at time of diagnosis, returned to normal after 16 weeks of treatment. The performance status stabilized and intravenous alimentation could be discontinued.ConclusionOur experience from one patient with CC suggests, that a combination of cytotoxic chemotherapy together with cetuximab may show promising efficacy in respect to survival and quality of life. Therefore cetuximab, as a component of palliative chemotherapy in biliary tract cancer, needs further evaluation in prospective randomized trials.

Retrospective analysis of systemic chemotherapy for unresectable advanced biliary tract cancer

4159 Background: Standard chemotherapy for biliary tract cancer (BTC) has not yet established. This study retrospectively examined the results of non-surgical treatments in patients with advanced BTC in order to clarify the relationship between treatment methods and prognosis following chemotherapy using historical controls. Methods: All patients receiving non-surgical treatments between April 2000 and March 2003 were examined in a multi-center review. The treatment methods, results and prognoses were analyzed. Survival from the start of the treatment was calculated by the Kaplan-Meier method. Results: Four hundred-twenty nine patients were recorded; 129 intrahepatic cholangiocarcinomas, 102 extrahepatic cholangiocarcinomas, 177 gall bladder cancers (GBC), and 22 ampulary papilla of Vater cancers. Systemic chemotherapy was administered to 211 (49.2%) patients, best supportive care to 143 (33.3%), radiotherapy or chemoradiotherapy to 62 (14.4%), hepatic arterial infusion chemotherapy to 11 (2.6%), and treatment was unknown in 2 (0.5%). Systemic chemotherapy regimens consisted of gemcitabine alone in 66 patients, CDDP-based in 47, 5FU-based in 34, FAM in 30, S-1 in 22, and other agents in 12. The overall response rate was 9.5% (20 partial responses), while the response rates of S-1 and FAM were both over 15%; S-1 was 18% and FAM 17%. The overall median survival time was 8.1 months, and the 1-year survival rate was 29.3%. There was no significant difference in survival among the regimens. Prognosis of GBC patients was significantly poorer than those with other BTCs. Conclusions: The response to chemotherapy and the prognosis of unresectable BTC patients were comparable to those of locally advanced or metastatic pancreatic cancer patients. A multi-center clinical trial is now on planning to optimize the use of BTC cancer resources in Japan. No significant financial relationships to disclose.