Chemotherapy For Advanced Biliary Cancer Research Articles

Second line chemotherapy for advanced biliary cancer: FOLFOX versus FOLFIRI: Analysis of retrospective and prospective data

Aim. To evaluate the efficacy and toxicity of second-line polychemotherapy according to FOLFOX or FOLFIRI regimen in patients with biliary tract tumours after progression during first-line chemotherapy (CT). Materials and methods. The study is based on the analysis of retrospective and prospective data on the examination and treatment of 94 patients with biliary cancer of grades T1-4N0-2M0-1 followed-up and treated at the N.N. Blokhin National Medical Research Center of Oncology from 2015 to 2023. All patients were divided into 2 groups: Group 1 (FOLFOX, n=47) and Group 2 (FOLFIRI, n=47). In Group 1, patients received the recommended FOLFOX second-line CT regimen. Patients in Group 2 received FOLFIRI regimen. The endpoints were overall survival (OS) and incidence of grade 3-4 adverse events. Results. The study included 94 patients. In the FOLFOX group, the median OS was 13.0 months (1-year OS was 57.8±7.4%); for the FOLFIRI group, the median OS was 12.3 months (1-year OS was 54.4±7.3%). The toxicity profiles of FOLFOX and FOLFIRI were acceptable and consistent with those reported for the regimens. According to the grade 3–4 toxicity data, diarrhea was significantly more common in the FOLFIRI group (p=0.014), and neurotoxicity was more common in the FOLFOX group (p=0.006). During the second-line CT, the frequency of grade 1–4 toxicities in the groups did not differ: 18 (38.3%) events in the FOLFOX group and 19 (40.0%) events in the FOLFIRI group. Conclusion. Our results of evaluating the efficacy and toxicity of the second-line polychemotherapy regimens show that the FOLFOX and FOLFIRI CT regimens have equal efficacy in patients with advanced biliary tract cancer with a good performance according to the ECOG scale, who previously received the first-line therapy with a combination of gemcitabine with a platinum agent (cisplatin or oxaliplatin); also, our data demonstrate similar toxicity profiles of these regimens.

Development and Multicentre Validation of the Modena Score to Predict Survival in Advanced Biliary Cancers Undergoing Second-Line Chemotherapy.

BackgroundThe role of second-line chemotherapy in advanced biliary cancers (ABCs) has only recently been established in phase III randomized trial and the optimal selection of patients most likely to benefit from it remains challenging.MethodsA cohort of 98 ABC treated second-line chemotherapy was used as a developmental dataset to identify covariates independently associated with overall survival (OS). Kaplan–Meier analysis was used to investigate the association between variables and OS and those retaining statistically significance were combined in a multiplexed score.ResultsThe following pretreatment variables were independently associated with OS: ECOG PS > 0, peritoneal disease, LDH > 430 UI/L, albumin <3.5 gr/dL, gamma-GT >100 UI/L, sodium <140 mEq/L, absolute lymphocyte count <1000/mmc, and PFS to first-line <6 months. Based on these results, a scoring system was developed that identified three subgroups with statistically different OS: low-risk (mOS 18 months), intermediate-risk (mOS 9.4 months) and high-risk (mOS 2.9 months) (p < 0.001). The prognostic model was both internally and externally validated in a multicentre cohort of 120 ABCs.ConclusionThe Modena score is a multiplexed scoring system capable of accurately risk-stratified ABCs treated with second-line chemotherapy. Based on its reproducibility, usability and generalizability, it has the potential for assisting therapeutic decision-making in the clinic and risk-stratification in future trials.

Third-line chemotherapy in advanced biliary cancers (ABC): pattern of care, treatment outcome and prognostic factors from a multicenter study

ABSTRACT Objectives Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy. Methods Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan–Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables. Results Among 101 pts included in the analysis. 68 (67.3%), 19 (18.8%) and 14 (13.8%) had intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. Atotal of 63 (62.3%) pts received monochemotherapy, while 38 (37.6%) were treated with adoublet. The median OS and PFS were 5 and 3 months, respectively. Disease control rate was achieved in 23 (22.7%) pts, with 2 (2%) partial responses. Grade 3–4 treatment-related adverse events were reported in 22 (21.7%) pts. At multivariate analysis, ECOG PS (p < 0.001), tumor burden (p = 0.01) and lymphocyte-to-monocyte ratio (p =0.02) were independent predictors of survival. Conclusions Third-line chemotherapy displayed limited activity in this real-world cohort, although prognostic factors have been identified that may assist in treatment decision. The results of this multicenter experience, highlight the need for more effective therapies and provide a benchmark for future trials in this setting.

57P Third-line chemotherapy in advanced biliary cancers (ABC): Pattern of care, treatment outcome and prognostic factors from a multicenter study

57P Third-line chemotherapy in advanced biliary cancers (ABC): Pattern of care, treatment outcome and prognostic factors from a multicenter study

The prognostic nutritional index predicts survival and response to first-line chemotherapy in advanced biliary cancer.

An accurate risk-stratification is key to optimize the benefit-to-risk ratio of palliative treatment in advanced biliary cancer. We aimed at assessing the impact of the prognostic nutritional index (PNI) on survival and treatment response in advanced biliary cancer (ABC) receiving first-line chemotherapy. Medical records of ABC treated with standard chemotherapy at the Modena Cancer Centre were retrospectively reviewed for variables deemed of potential interest, including the PNI. Univariate and multivariate analyses were performed to investigate the association between the covariates and overall survival (OS). 114 ABC fulfilled the inclusion criteria and made up the training cohort. A PNI cut-off value of 36.7 was established using the receiver operating characteristic (ROC) analysis. At both the univariate and the multivariate analysis, low PNI value (<36.7) was associated with shorter OS (P=.0011), together with increased NLR (P=.0046) and ECOG>1 (P<.0001). The median OS was 5.4 vs 12.1months in the low- vs high PNI-group. Moreover, a PNI value>36.7 resulted in a higher disease control in patients treated with gemcitabine/platinum combination (61.4% vs 34.3%). These results were validated in an independent cohort of 253 ABC. We demonstrated and externally validated a prognostic role for the PNI in ABC treated with first-line chemotherapy. Although the PNI turned out to be predictive in the subset of patients receiving platinum/gemcitabine combination, future prospective confirmation is needed.

Impact of adjuvant chemotherapy using gemcitabine plus S-1 after surgical resection for advanced biliary cancer.

132 Background: The impact of adjuvant chemotherapy for advanced biliary cancer remains controversial. We previously failed to show survival benefit of adjuvant gemcitabine chemotherapy (UMIN000014018). The aim of this study was to evaluate the safety and efficacy of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for advanced biliary cancer. Methods: Between January 2006 and May 2019, a total of 110 patients who underwent surgical resection for biliary cancer (UICC Stage II or more) were enrolled in this study. Of these, 33 patients subsequently received 12 cycles of adjuvant chemotherapy (GS group), and 77 patients underwent surgery alone (S group). A cycle of chemotherapy consisted of oral S-1 70mg/m2 for 7 consecutive days and intravenous gemcitabine 1000mg/m2 on day 7, followed by a 1-week break from chemotherapy. Clinicopathological factors and patient survival were compared between the two groups. Results: GS group had significantly younger patients ( P = 0.036) and higher UICC T factor ( P = 0.001). Surgical procedure was significantly different in the two groups (P = 0.010). Other patient demographics and tumor characteristics were similar between the two groups. The completion rate of adjuvant chemotherapy was 57.6%, and there was no treatment-related deaths. All grades and grade 3/4 adverse event were seen in 60.6% and 33.3%, respectively. Three-year recurrence-free and overall survival rates were significantly higher in GS group than S group (61.9% vs. 34.4%, P = 0.016; 77.6% vs. 39.7%, P &lt; 0.001, respectively). Conclusions: Adjuvant chemotherapy using gemcitabine plus S-1 was well tolerated and it would be an effective treatment strategy for the patients with resected advanced biliary cancer. Based on these results, randomized controlled study should be warranted.

Second-line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes.

Although gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers. Institutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second-line chemotherapy (OS2) was estimated with Kaplan-Meier methods. This study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11months (95% confidence interval [CI], 8.8-13.1months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4months (95% CI, 10.7-17.8months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8months; 95% CI, 5-10.6months) or gallbladder carcinoma (9.4months; 95% CI, 7.2-12.3months; P=.018). The median time to second-line treatment failure was 2.2months (95% CI, 1.8-2.7months), and it was similar across tumor locations (P=.60). In this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first-line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second-line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials.

Second-line chemotherapy (CTx) outcomes in advanced biliary cancers (ABC): A retrospective multicenter analysis.

437 Background: While gemcitabine in combination with platinum has been well established as first line systemic therapy for ABC, there remains no standard of care regimen in the second line setting. We evaluated current practice and outcomes for second line chemotherapy in patients with ABC across three geographically diverse, large US academic medical centers. Methods: 198 pts who received second line chemotherapy for ABC after 1/1/11 were identified from institutional databases following IRB approval. Records were reviewed for demographic, treatment and response data. Overall survival (OS) was calculated from start of second line chemotherapy and estimated using Kaplan-Meier methods. Results: Median follow up among survivors was 5 months and median OS for all patients from start of second line therapy was 11 months (mo) (95% CI 8.8-13.1): intrahepatic (61.1%): 13.4 mo (95%CI: 10.7-17.8); extrahepatic (14.1%): 6.8 mo (95%CI: 5-11); and gallbladder (24.8%): 9.4 mo (95%CI: 7.2-12.3). Median duration of second line chemotherapy was 2.2 mo (range 0-32.5). 103 pts (52%) received ≥ 3 lines of chemotherapy. Median OS from start of first line of gemcitabine plus cisplatin or oxaliplatin was 22.4 mo (95% CI 17.9 – 25.5). Conclusions: In highly selected pts with ABC treated at academic medical centers, survival following progression on first line chemotherapy was higher than previously reported, and patients received multiple lines of treatment. This multicenter collaboration provides a contemporary benchmark to inform the hypotheses and design of future clinical trials of second line chemotherapy in ABC. [Table: see text]

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data

BackgroundAfter progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far.MethodsWe collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings.ResultsA total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months).ConclusionsThe current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

Fixed dose rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced biliary cancer

e15581 Background: Biliary cancer is diagnosed at advanced stage and recurrence is common after surgical resection. Gemcitabine and UFT combination chemotherapy showed promising results in advanced pancreatic cancer(APC) and fixed dose- rate(FDR) infusion(10mg/m2/min) of gemcitabine is more effective than 30min-infusion in APC patients. We conducted a prospective multicenter phase II study to evaluate the efficacy and toxicity of FDR gemcitabine and UFT combination chemotherapy in advanced biliary cancer(ABC) patients. We evaluated the quality of life(QOL) and relationship between treatment outcome and polymorphisms of DNA repair gene such as RecQ1, RAD54L, XRCC1 and ATM. Methods: We included the chemo-naive patients with measurable metastatic or recurrent biliary adenocarcinoma except gall bladder cancer. Patients received gemcitabine infusion of rate of 10mg/m2/min on day 1, 8, and 15 plus oral UFT (400mg/m2) on day 1 to 21. We used modified PCR-RFLP method to evaluate the polymorphism of DNA repair gene. The primary endpoint was response rate. Results: From October 2006 to March 2008, 47 patients were enrolled and 33 of them were included in this analysis. Median age was 58 years(range 33–73 years) and 18 patients were male. Partial response was 24.2% and disease control rate was 51.5%. The estimated median time to progression(TTP) was 87 days(95% CI 51–123). Median overall survival was 243 days(95% CI 114–372). Grade 3/4 neutropenia was observed in 12 of 33 patients(36.4%) and 17 times of 114 cycles of chemotherapy(14.9%). No febrile neutropenia was observed. Grade 3/4 thrombocytopenia occurred in 5 patients(15.2%). Non-hematologic toxicities were mild. Polymorphism of XRCC1 was related to TTP(TTP of wild, heterozygous variant and homozygous variant type was 162, 71 and 25 days, respectively. p=0.0039). QOL as a secondary endpoint was not analyzed at this time. Conclusions: FDR infusion of gemcitabine and UFT combination chemotherapy in chemo-naïve patients with ABC is a well-tolerated and effective regimen. No significant financial relationships to disclose.

Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer

A phase II study was conducted to assess the efficacy and tolerability of substituting capecitabine for 5-fluorouracil in combination with cisplatin in patients with advanced biliary cancer. Patients with previously untreated metastatic or unresectable measurable biliary adenocarcinoma received oral capecitabine 1250 mg/m(2) twice daily on days 1-14, and intravenous cisplatin 60 mg/m(2) on day 1. This cycle was repeated every 21 days. Forty-two patients were enrolled in this study. Of these, 38 were assessable for efficacy and 41 were assessable for safety. A median of three cycles of treatment (range one to eight) were administered. One patient achieved a complete response, and eight had partial responses, giving an overall response rate of 21.4% in the intention-to-treat population (95% confidence interval 9.1% to 33.9%). The median response duration was 5.1 months. The median time to progression and median overall survival were 3.7 and 9.1 months, respectively. The most common grade 3/4 adverse events were neutropenia (20% of patients), vomiting (12%), diarrhea (7%) and stomatitis (5%). There were no treatment-related deaths. The combination of capecitabine and cisplatin has promising antitumor activity and is well tolerated in patients with advanced biliary cancer.