Dataset Information

RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin.

ABSTRACT: The combination of gemcitabine plus cisplatin (GP) is regarded as a first-line treatment for patients with unresectable or recurrent biliary tract cancer (BTC). Several proteins including human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (DCK), cytidine deaminase (CDA), and ribonucleotide reductase subunit 1 (RRM1) are known to be involved in gemcitabine uptake and metabolism. This study was aimed to identify the predictive and prognostic values of these biomarkers in patients who treated with GP for advanced BTC. Tumor samples were obtained from 34 patients with unresectable or recurrent BTC who were treated with GP between August 2015 and February 2018. Intratumoral expression of hENT1, DCK, CDA and RRM1 was determined by immunohistochemistry and analyzed for association with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Median OS was significantly longer in the RRM1-negative group than in the RRM1-positive (9.9 months vs. 5.9 months, p = 0.037). Multivariate adjustment analyses also demonstrated RRM1 expression as an independent prognostic factor for OS in patients treated with GP chemotherapy. Increased intratumoral expression of RRM1 on immunohistochemical staining may be a biomarker predicting poor survival in patients with GP chemotherapy for advanced BTC. Large-scale well-predefined prospective research is needed to validate the utility of biomarkers in clinical practice.

SUBMITTER: Chun JW

PROVIDER: S-EPMC8538709 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin.

Chun Jung Won JW Lee Boyoung B Park Weon Seo WS Han Nayoung N Hong Eun Kyung EK Park Eun Young EY Han Sung Sik SS Park Sang-Jae SJ Kim Tae Hyun TH Lee Woo Jin WJ Woo Sang Myung SM

Journal of clinical medicine 20211011 20

The combination of gemcitabine plus cisplatin (GP) is regarded as a first-line treatment for patients with unresectable or recurrent biliary tract cancer (BTC). Several proteins including human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (DCK), cytidine deaminase (CDA), and ribonucleotide reductase subunit 1 (RRM1) are known to be involved in gemcitabine uptake and metabolism. This study was aimed to identify the predictive and prognostic values of these biomarkers in pa ...[more]

PMID: 34682775

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Project description:BACKGROUND:The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptably low. This study aimed to determine the efficacy, safety and predictive biomarkers of the immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs. METHODS:In this open-label, single-arm, phase II trial, a chemotherapy and immunotherapy combination consisting of gemcitabine 1000 mg/m2, cisplatin 75 mg/m2 and nivolumab 3 mg/kg was administered every 3 weeks for up to six cycles. Maintenance treatment with gemcitabine plus nivolumab was administered to patients achieving disease control following the combination therapy. The primary outcome was the objective response rate. Secondary outcomes included safety, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). The exploratory objective was to assess biomarkers for predicting clinical response and prognosis. RESULTS:Thirty-two patients with a median age of 60 (range 27-69) years were enrolled. As of September 31, 2019, the median follow-up was 12.8 (95% CI 10.8 to 14.8) months. Twenty-seven response-evaluable patients received a median of 4 (IQR, 3-6) cycles of combination therapy, of whom 15 (55.6%) patients achieved an objective response, including 5 (18.6%) with a complete response (CR), and the DCR was 92.6%. Of the six patients in cohort A who were resistant to gemcitabine-based or cisplatin-based chemotherapy, one achieved CR and one achieved partial response. Thirteen of 21 chemotherapy-naive patients (61.9%) in cohort B achieved an objective response. The median PFS of all patients in cohorts A+B was 6.1 months. The median OS was 8.5 months, with a 33.3% 12-month OS rate. The most frequent grade 3 or higher adverse events were thrombocytopenia (56%) and neutropenia (22%). Fitness might be a biomarker for predicting clinical response. On-therapy changes in serum soluble FasL, MCP-1 and interferon-? were correlated with prognosis. CONCLUSIONS:Nivolumab in combination with gemcitabine and cisplatin offers promising efficacy and a manageable safety profile for patients with advanced BTCs. TRIAL REGISTRATION NUMBER:NCT03311789.

Project description:BackgroundBiliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC.MethodsPatients initially received gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.ResultsOverall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.ConclusionAdjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.Trial registrationThe study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 ).

Project description:BackgroundA recent phase II trial reported prolonged survival in patients with advanced biliary tract cancer (BTC) following treatment with nab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P). We aimed to evaluate the clinical outcomes of Gem/Cis/nab-P in Asian patients with advanced BTC in a real-world setting.MethodsWe reviewed the data of patients who received Gem/Cis/nab-P for the management of advanced BTC between September 2019 and April 2021 at four institutes in Korea. Patients were classified into the Gem/Cis/nab-P and nab-P addition groups depending on the starting point of nab-P administration.ResultsA total of 178 patients treated with Gem/Cis/nab-P were included in the study. Of these, 43.8% had intrahepatic cholangiocarcinoma (CCA), 34.8% had extrahepatic CCA, and 21.3% had gall bladder cancer. A total of 117 (65.7%) patients received Gem/Cis/nab-P as the first-line treatment, while 61 (34.3%) were treated with gemcitabine-cisplatin-based chemotherapy followed by nab-P addition. The objective response rate (ORR) and disease control rate in all patients were 42.1% and 84.8%, respectively. The ORR in the Gem/Cis/nab-P group was 47.9%, while that in the nab-P addition group was 31.1%. The median progression-free survival and overall survival were 8.5 months [95% confidence interval (CI), 6.9-10.1] and 14.6 months (95% CI, 10.2-19.0), respectively. In patients who received Gem/Cis/nab-P as initial treatment, the median PFS was 9.4 months (95% CI, 7.9-10.9) and the median OS was not-reached (95% CI, not available). Anemia (n = 42, 23.6%), neutropenia (n = 40, 22.5%), and thrombocytopenia (n = 16, 9.0%) were the most common grade 3-4 toxicities. A total of 20 patients (11.2%) had conversions from unresectable to resectable disease and underwent surgery with curative intent.ConclusionGem/Cis/nab-P showed favorable real-life efficacy and safety outcomes in Korean patients with advanced BTC, which was consistent with the phase II trial outcomes.

Dataset Information

RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin.

Publications

RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin.

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