Cisplatin In Biliary Tract Cancer Research Articles

55P Subsequent anticancer therapy (SAT) analysis from 3-year follow-up of the phase III TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in biliary tract cancer (BTC)

55P Subsequent anticancer therapy (SAT) analysis from 3-year follow-up of the phase III TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in biliary tract cancer (BTC)

P-69 Efficacy and safety of S-1 following gemcitabine with cisplatin for biliary tract cancer

The combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). Although there is no standard second-line therapy in Japan, S-1 is often used in clinical practice based on the results of some clinical studies investigating the efficacy and safety of S-1 following gemcitabine monotherapy. These studies showed the median progression-free survival and overall survival were 2.3-5.5 and 6.0-13.5 months, respectively, and overall response rate (ORR) was 4-22.7%.

Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer

PurposeJab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied.Materials and MethodsWe performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.ResultsAmong 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression.ConclusionJab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.

715P - Jab1 silencing inhibits proliferation and sensitizes to cisplatin in biliary tract cancer

715P - Jab1 silencing inhibits proliferation and sensitizes to cisplatin in biliary tract cancer

723P - Gemcitabine Plus Cisplatin Versus Capcitbine Plus Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer

ABSTRACT Aim: Combination chemotherapy with gemcitabine and cisplatin is regarded as a standard chemotherapy for patients with advanced biliary tract cancer (BTC). Results of phase 2 trials of 5-FU or its derivatives combined with cisplatin in BTCs have shown modest benefits. It remains unclear whether capecitabine combined with cisplatin would show similar effects compared with standard therapy using gemcitabine with cisplatin. Methods: A clinical database was used to identify all patients with locally advanced or metastatic BTC (cholangiocarcnoma, gallbladder cancer) who treated with first-linechemotherapy in the Asan Medical Center. All patients received either cisplatin (25mg/m2) followed by gemcitabine (1000mg/m2), each administered on days 1 and 8 every 3 weeks (GP-W group), or capecitabine (1000 mg/m2 twice daily) on days 1-14, and cisplatin (60 mg/m2) on day 1 every 3 weeks (XP group). Patients' medical characteristics, radiological responses, and survival status were analyzed. Results: Of the 134 patients who met the inclusion criteria, 78 received XP and the other 56 were treated with GP-W. There were gallbladder cancer (25 [32%]) and cholangiocarcinoma (53 [68%]) in XP group, 15[27%] and 41[73%] in GP-W group (P = 0.57). The two groups were balanced including site of tumor except for a higher proportion of patients with relapsed setting in XP group (29 [37%] vs 6 [11%]). After a median follow-up duration of 26.2 months (95% CI 24.2-28.2), progression-free survival (PFS) was 5.7 month (95% C.I. 4.3 – 7.1) for XP and 4.1 month (95% C.I. 3.0 – 5.2) for GP-W. (hazard ratio [HR, GP-W vs XP] 0.81, 95% CI, 0.55-1.21, P = 0.31). The overall survival (OS) was 11.0 months (95% CI 7.1 - 14.9) for XP and 9.8 months (95% C.I. 7.5 - 12.2) for GP-W. (HR = 0.84, 95% CI 0.57–1.23, P = 0.36). The two groups showed same response rates (XP vs GP-W, 7 [9%] vs 5 [9%]) and were not stastically different in terms of disease control rate (75% vs 74%, P = 1.00). Conclusions: The XP regimen seems to be as effective as GP-W in patients with advanced BTC. The XP regimen might be a viable option due to efficacy and conveniance, such as one visit schedule per one cycle. Disclosure: All authors have declared no conflicts of interest.

Combination of gemcitabine and cisplatin for biliary tract cancer: A platform to build on

Background: There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression free survival, the trial was extended to the phase 3 trial reported here. Methods: We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival. Results: After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52-0.80; p <0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (p <0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, p = 0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups. Conclusions: As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer.