{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:56:21Z","timestamp":1781650581439,"version":"3.54.5"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":43,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Anhui Province Key Project for Inheritance and Innovation of Traditional Chinese Medicine Research","award":["2024CCCX006"],"award-info":[{"award-number":["2024CCCX006"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Off-label afatinib with tegafur was attempted as a last resort option in a patient with advanced gallbladder cancer, achieving satisfactory outcomes. This study evaluated the benefits and toxicity of afatinib with tegafur in advanced biliary tract cancer (BTC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included patients who received afatinib combined with tegafur after failure of gemcitabine-based systemic therapy between Oct 2017 and Dec 2024 at the First Affiliated Hospital of Anhui Medical University. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events were evaluated. Cox regression analysis and subgroup analysis were used to assess the relationship between different factors and OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-eight patients were included. Two patients achieved partial response, 28 achieved stable disease, and 28 achieved progressive disease, indicating a DCR of 51.7% and an ORR of 3.4%. Median PFS and OS were 4.0 and 6.6 months, respectively. The toxicity associated with afatinib and tegafur was generally acceptable. OS was prolonged in six patients with positive HER-2 and four patients with positive KRAS (G13D) mutations (median: 11.0 months) compared with those without mutations (median: 6.30 months) or unknown genetic status (median: 6.30 months) (\n                      <jats:italic>P\u2009=<\/jats:italic>\n                      \u20090.013). The multivariable Cox analysis showed that\n                      <jats:italic>n<\/jats:italic>\n                      o factors were independently associated with OS (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Afatinib with tegafur had an acceptable safety profile for advanced BTC after gemcitabine-based systemic therapy failure. The outcome of patients with low performance status and HER-2 or KRAS (G13D) mutations may be better than patients without the mutation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-026-05039-4","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T06:44:39Z","timestamp":1776581079000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tolerance and response of afatinib combined with tegafur in patients with advanced biliary tract cancer after failure of gemcitabine-based systemic therapy"],"prefix":"10.1007","volume":"17","author":[{"given":"Zhizheng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaosheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"issue":"6","key":"5039_CR1","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1007\/s11523-023-01000-5","volume":"18","author":"V Peirce","year":"2023","unstructured":"Peirce V, Paskow M, Qin L, Dadzie R, Rapoport M, Prince S, et al. A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer. Target Oncol. 2023;18(6):837\u201352.","journal-title":"Target Oncol"},{"issue":"2","key":"5039_CR2","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.annonc.2022.10.506","volume":"34","author":"A Vogel","year":"2023","unstructured":"Vogel A, Bridgewater J, Edeline J, Kelley RK, Klumpen HJ, Malka D, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(2):127\u201340.","journal-title":"Ann Oncol"},{"issue":"3","key":"5039_CR3","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u201363.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"5039_CR4","first-page":"10","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10\u201345.","journal-title":"CA Cancer J Clin"},{"key":"5039_CR5","doi-asserted-by":"publisher","unstructured":"Siddiqui A, Sanyal S, Mukherjee D, Dwivedi M, Dwivedi M. The genetic and epidemiological dimensions of gallbladder cancer: toward effective therapeutic strategies. Curr Gene Ther; 2025. https:\/\/doi.org\/10.2174\/0115665232366089250610083533","DOI":"10.2174\/0115665232366089250610083533"},{"issue":"6","key":"5039_CR6","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1080\/0284186X.2017.1418532","volume":"57","author":"J Dierks","year":"2018","unstructured":"Dierks J, Gaspersz MP, Belkouz A, van Vugt JLA, Coelen RJS, de Groot JWB, et al. Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin. Acta Oncol (Stockholm Sweden). 2018;57(6):807\u201312.","journal-title":"Acta Oncol (Stockholm Sweden)"},{"issue":"1","key":"5039_CR7","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12885-017-3266-9","volume":"17","author":"MG McNamara","year":"2017","unstructured":"McNamara MG, Bridgewater J, Lopes A, Wasan H, Malka D, Jensen LH, et al. Systemic therapy in younger and elderly patients with advanced biliary cancer: sub-analysis of ABC-02 and twelve other prospective trials. BMC Cancer. 2017;17(1):262.","journal-title":"BMC Cancer"},{"issue":"1","key":"5039_CR8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/ajco.12592","volume":"13","author":"K Park","year":"2017","unstructured":"Park K, Kim KP, Park S, Chang HM. Comparison of gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer. Asia-Pac J Clin Oncol. 2017;13(1):13\u201320.","journal-title":"Asia-Pac J Clin Oncol"},{"issue":"2","key":"5039_CR9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.21037\/cco-22-93","volume":"12","author":"M LaPelusa","year":"2023","unstructured":"LaPelusa M, Heumann T, Goff L, Agarwal R. Targeted therapies in advanced biliary tract cancers-a narrative review. Chin Clin Oncol. 2023;12(2):14.","journal-title":"Chin Clin Oncol"},{"issue":"1","key":"5039_CR10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1634\/theoncologist.2020-0379","volume":"26","author":"J Cadranel","year":"2021","unstructured":"Cadranel J, Liu SV, Duruisseaux M, Branden E, Goto Y, Weinberg BA, et al. Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series. Oncologist. 2021;26(1):7\u201316.","journal-title":"Oncologist"},{"issue":"12","key":"5039_CR11","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1016\/j.annonc.2020.08.2335","volume":"31","author":"J Laskin","year":"2020","unstructured":"Laskin J, Liu SV, Tolba K, Heining C, Schlenk RF, Cheema P, et al. NRG1 fusion-driven tumors: biology, detection, and the therapeutic role of afatinib and other ErbB-targeting agents. Ann Oncol. 2020;31(12):1693\u2013703.","journal-title":"Ann Oncol"},{"issue":"6","key":"5039_CR12","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1177\/1078155220931926","volume":"26","author":"RD Harvey","year":"2020","unstructured":"Harvey RD, Adams VR, Beardslee T, Medina P. Afatinib for the treatment of EGFR mutation-positive NSCLC: A review of clinical findings. J Oncol Pharm Pract. 2020;26(6):1461\u201374.","journal-title":"J Oncol Pharm Pract"},{"issue":"36","key":"5039_CR13","doi-asserted-by":"publisher","first-page":"58007","DOI":"10.18632\/oncotarget.11157","volume":"7","author":"AR Nam","year":"2016","unstructured":"Nam AR, Kim JW, Cha Y, Ha H, Park JE, Bang JH, et al. Therapeutic implication of HER2 in advanced biliary tract cancer. Oncotarget. 2016;7(36):58007\u201321.","journal-title":"Oncotarget"},{"issue":"4","key":"5039_CR14","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.21037\/tcr-23-2019","volume":"13","author":"F Cao","year":"2024","unstructured":"Cao F, Gu C, Hong W, Jin Y. Advances in monotherapy and combination therapy of S-1 for patients with advanced non-small cell lung cancer: a narrative review. Transl Cancer Res. 2024;13(4):2012\u201325.","journal-title":"Transl Cancer Res"},{"issue":"10","key":"5039_CR15","doi-asserted-by":"publisher","first-page":"6483","DOI":"10.21037\/jtd-24-940","volume":"16","author":"F Cao","year":"2024","unstructured":"Cao F, Wang W, Gu C, Zhou Y, Jin Y, Hong W. Efficacy and outcome analysis: monotherapy and combination therapy of S-1 for patients with advanced non-small cell lung cancer. J Thorac Dis. 2024;16(10):6483\u201395.","journal-title":"J Thorac Dis"},{"issue":"10372","key":"5039_CR16","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0140-6736(22)02038-4","volume":"401","author":"K Nakachi","year":"2023","unstructured":"Nakachi K, Ikeda M, Konishi M, Nomura S, Katayama H, Kataoka T, et al. Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2023;401(10372):195\u2013203.","journal-title":"Lancet"},{"issue":"12","key":"5039_CR17","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1093\/annonc\/mdz402","volume":"30","author":"C Morizane","year":"2019","unstructured":"Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, et al. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced\/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019;30(12):1950\u20138.","journal-title":"Ann Oncol"},{"issue":"4","key":"5039_CR18","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1177\/1534735418801532","volume":"17","author":"H Lu","year":"2018","unstructured":"Lu H, Qin J, Han N, Xie F, Gong L, Li C. Banxia Xiexin Decoction Is Effective to Prevent and Control Irinotecan-Induced Delayed Diarrhea in Recurrent Small Cell Lung Cancer. Integr cancer Ther. 2018;17(4):1109\u201314.","journal-title":"Integr cancer Ther"},{"issue":"1","key":"5039_CR19","first-page":"46","volume":"30","author":"YY Zhang","year":"1995","unstructured":"Zhang YY, Li SH, Tian Z. Morphological and histological studies of the Chinese drug lao-guan-cao. Yao Xue Xue bao Acta Pharm Sinica. 1995;30(1):46\u201358.","journal-title":"Yao Xue Xue bao Acta Pharm Sinica"},{"issue":"2","key":"5039_CR20","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s12072-023-10633-7","volume":"18","author":"Y Mao","year":"2024","unstructured":"Mao Y, Ma S, Liu C, Liu X, Su M, Li D, et al. Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update. Hepatol Int. 2024;18(2):384\u2013419.","journal-title":"Hepatol Int"},{"issue":"5","key":"5039_CR21","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s00280-018-3566-z","volume":"81","author":"R Matsuyama","year":"2018","unstructured":"Matsuyama R, Morioka D, Mori R, Hiratani S, Yabushita Y, Ota Y, et al. Single-institution experience with gemcitabine-cisplatin combination therapy as a second-line treatment for patients with unresectable biliary tract cancer after failure of gemcitabine-S-1 combination therapy: a prospective feasibility study. Cancer Chemother Pharmacol. 2018;81(5):949\u201355.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"6","key":"5039_CR22","doi-asserted-by":"publisher","first-page":"555","DOI":"10.5582\/bst.2024.01376","volume":"18","author":"R Xu","year":"2025","unstructured":"Xu R, Zhou J, Yang J, Yu Y, Wang H, Zhang Z, et al. First-line systemic therapy and sequencing options in advanced biliary tract cancer: A systematic review and network meta-analysis. Biosci Trends. 2025;18(6):555\u201362.","journal-title":"Biosci Trends"},{"issue":"5","key":"5039_CR23","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1001\/jamaoncol.2023.0016","volume":"9","author":"J Hyung","year":"2023","unstructured":"Hyung J, Kim I, Kim KP, Ryoo BY, Jeong JH, Kang MJ, et al. Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer: The Phase 2b NIFTY Randomized Clinical Trial. JAMA Oncol. 2023;9(5):692\u20139.","journal-title":"JAMA Oncol"},{"issue":"6","key":"5039_CR24","doi-asserted-by":"publisher","first-page":"103488","DOI":"10.1016\/j.esmoop.2024.103488","volume":"9","author":"A Vogel","year":"2024","unstructured":"Vogel A, Sahai V, Hollebecque A, Vaccaro GM, Melisi D, Al Rajabi RM, et al. An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202. ESMO Open. 2024;9(6):103488.","journal-title":"ESMO Open"},{"issue":"6","key":"5039_CR25","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/S1470-2045(20)30157-1","volume":"21","author":"GK Abou-Alfa","year":"2020","unstructured":"Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796\u2013807.","journal-title":"Lancet Oncol"},{"issue":"5","key":"5039_CR26","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s00280-023-04633-5","volume":"93","author":"B Fan","year":"2024","unstructured":"Fan B, Abou-Alfa GK, Zhu AX, Pandya SS, Jia H, Yin F, et al. Pharmacokinetics\/pharmacodynamics of ivosidenib in advanced IDH1-mutant cholangiocarcinoma: findings from the phase III ClarIDHy study. Cancer Chemother Pharmacol. 2024;93(5):471\u20139.","journal-title":"Cancer Chemother Pharmacol"},{"key":"5039_CR27","doi-asserted-by":"publisher","first-page":"176727","DOI":"10.1016\/j.ejphar.2024.176727","volume":"979","author":"MA Hossain","year":"2024","unstructured":"Hossain MA. Targeting the RAS upstream and downstream signaling pathway for cancer treatment. Eur J Pharmacol. 2024;979:176727.","journal-title":"Eur J Pharmacol"},{"key":"5039_CR28","doi-asserted-by":"publisher","first-page":"117955492513483","DOI":"10.1177\/11795549251348367","volume":"19","author":"IL Tsai","year":"2025","unstructured":"Tsai IL, Lin CY, Su PL, Lin CC, Chang JW, Huang CY, et al. Real-World Efficacy and Safety of S-1 Monotherapy in Non-Small Cell Lung Cancer Management: Insights From a Multicenter Retrospective Cohort Study. Clin Med Insights Oncol. 2025;19:11795549251348367.","journal-title":"Clin Med Insights Oncol"},{"issue":"12","key":"5039_CR29","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1007\/s12094-024-03482-9","volume":"26","author":"M Xu","year":"2024","unstructured":"Xu M, Wang Y, Shao K, Hao Y, Song Z. Pyrotinib as a salvage treatment for patients with HER-2 positive advanced lung adenocarcinoma after the progression of afatinib treatment. Clin translational oncology: official publication Federation Span Oncol Soc Natl Cancer Inst Mexico. 2024;26(12):3050\u20137.","journal-title":"Clin translational oncology: official publication Federation Span Oncol Soc Natl Cancer Inst Mexico"},{"key":"5039_CR30","doi-asserted-by":"publisher","first-page":"107988","DOI":"10.1016\/j.lungcan.2024.107988","volume":"197","author":"A Hata","year":"2024","unstructured":"Hata A, Katakami N, Takase N, Kibata K, Yamanaka Y, Tamiya M, et al. Afatinib plus bevacizumab combination after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer: Phase II ABCD-study. Lung Cancer. 2024;197:107988.","journal-title":"Lung Cancer"},{"issue":"2","key":"5039_CR31","doi-asserted-by":"publisher","first-page":"e2037120","DOI":"10.1001\/jamanetworkopen.2020.37120","volume":"4","author":"K Sehgal","year":"2021","unstructured":"Sehgal K, Gill RR, Widick P, Bindal P, McDonald DC, Shea M, et al. Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy. JAMA Netw Open. 2021;4(2):e2037120.","journal-title":"JAMA Netw Open"},{"key":"5039_CR32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.ejca.2021.07.005","volume":"155","author":"O Sutcuoglu","year":"2021","unstructured":"Sutcuoglu O, Ozdemir N, Yazici O, Re. Post-progression outcomes of NSCLC patients with PD-L1 expression >\/=50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study. Eur J Cancer. 2021;155:294\u20135.","journal-title":"Eur J Cancer"},{"issue":"1","key":"5039_CR33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.21037\/hbsn-21-172","volume":"12","author":"W Zhang","year":"2023","unstructured":"Zhang W, Sun Y, Jiang Z, Qu W, Gong C, Zhou A. Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. Hepatobiliary Surg Nutr. 2023;12(1):37\u201344.","journal-title":"Hepatobiliary Surg Nutr"},{"issue":"4","key":"5039_CR34","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/bjc.2011.17","volume":"104","author":"G Kim Kp, Jang","year":"2011","unstructured":"Kim Kp, Jang G, Hong YS, Lim HS, Bae Ks, Kim HS, et al. Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the CYP2A6 polymorphism on pharmacokinetics and clinical activity. Br J Cancer. 2011;104(4):605\u201312.","journal-title":"Br J Cancer"},{"issue":"16","key":"5039_CR35","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1016\/j.ejca.2015.07.041","volume":"51","author":"A Suder","year":"2015","unstructured":"Suder A, Ang JE, Kyle F, Harris D, Rudman S, Kristeleit R, et al. A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours. Eur J Cancer. 2015;51(16):2275\u201384.","journal-title":"Eur J Cancer"},{"issue":"1","key":"5039_CR36","doi-asserted-by":"publisher","first-page":"257","DOI":"10.7150\/jca.27487","volume":"10","author":"W Zheng","year":"2019","unstructured":"Zheng W, Ying J, Zhou Y, Lu Z, Min K, Wang W, et al. The Efficacy and Safety of First-line Chemotherapies for Advanced Biliary Tract Cancer: A Network Meta-analysis. J Cancer. 2019;10(1):257\u201366.","journal-title":"J Cancer"},{"issue":"12","key":"5039_CR37","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.1093\/annonc\/mdu162","volume":"25","author":"A Lamarca","year":"2014","unstructured":"Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25(12):2328\u201338.","journal-title":"Ann Oncol"},{"issue":"1","key":"5039_CR38","doi-asserted-by":"publisher","first-page":"83","DOI":"10.4251\/wjgo.v12.i1.83","volume":"12","author":"JD Mizrahi","year":"2020","unstructured":"Mizrahi JD, Gunchick V, Mody K, Xiao L, Surapaneni P, Shroff RT, et al. Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers. World J Gastrointest Oncol. 2020;12(1):83\u201391.","journal-title":"World J Gastrointest Oncol"},{"issue":"18","key":"5039_CR39","doi-asserted-by":"publisher","first-page":"3290","DOI":"10.1002\/cncr.29471","volume":"121","author":"B Brieau","year":"2015","unstructured":"Brieau B, Dahan L, De Rycke Y, Boussaha T, Vasseur P, Tougeron D, et al. Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Ent\u00e9rologues Oncologues. Cancer. 2015;121(18):3290\u20137.","journal-title":"Cancer"},{"issue":"5","key":"5039_CR40","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/bjc.2016.446","volume":"116","author":"BJ Kim","year":"2017","unstructured":"Kim BJ, Yoo C, Kim K-p, Hyung J, Park SJ, Ryoo B-Y, et al. Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients. Br J Cancer. 2017;116(5):561\u20137.","journal-title":"Br J Cancer"},{"issue":"1","key":"5039_CR41","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41467-023-36399-y","volume":"14","author":"JJ Harding","year":"2023","unstructured":"Harding JJ, Piha-Paul SA, Shah RH, Murphy JJ, Cleary JM, Shapiro GI, et al. Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers. Nat Commun. 2023;14(1):630.","journal-title":"Nat Commun"},{"issue":"3","key":"5039_CR42","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1097\/CAD.0000000000001558","volume":"35","author":"L Liu","year":"2024","unstructured":"Liu L, Chen Y, Zhu X, Zhao L, Chen B. HER2-positive advanced biliary tract cancer responds to second-line pyrotinib therapy: a case report. Anticancer Drugs. 2024;35(3):298\u2013301.","journal-title":"Anticancer Drugs"},{"issue":"24","key":"5039_CR43","doi-asserted-by":"publisher","first-page":"4426","DOI":"10.1002\/cncr.32463","volume":"125","author":"MA Lowery","year":"2019","unstructured":"Lowery MA, Goff LW, Keenan BP, Jordan E, Wang R, Bocobo AG, et al. Second-line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes. Cancer. 2019;125(24):4426\u201334.","journal-title":"Cancer"},{"key":"5039_CR44","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s13046-015-0267-x","volume":"34","author":"L Fornaro","year":"2015","unstructured":"Fornaro L, Vivaldi C, Cereda S, Leone F, Aprile G, Lonardi S, et al. Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data. J Exp Clin Cancer Res. 2015;34:156.","journal-title":"J Exp Clin Cancer Res"},{"key":"5039_CR45","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/cancers15235543","volume":"15","author":"P Villalba Cuesta","year":"2023","unstructured":"Villalba Cuesta P, Avedillo Ruidiaz M, Ruiz Hisp\u00e1n E, Fuentes Mateos R, Lamarca A. Exploring the promise of second-line chemotherapy in biliary tract tumours: a glimpse into novel treatment approaches. Cancers (Basel). 2023;15:23.","journal-title":"Cancers (Basel)"},{"key":"5039_CR46","doi-asserted-by":"publisher","first-page":"175883592513680","DOI":"10.1177\/17588359251368069","volume":"17","author":"O Karhan","year":"2025","unstructured":"Karhan O, \u0130leri S, Urak\u00e7\u0131 Z, Sezgin Y, Y\u0131ld\u0131r\u0131m \u00dc, \u00dcnl\u00fc B, et al. Comparison of the efficacy of mFOLFOX-6 and mDCF regimens in the treatment of metastatic gastric cancer: a multicenter retrospective study. Ther Adv Med Oncol. 2025;17:17588359251368069.","journal-title":"Ther Adv Med Oncol"},{"key":"5039_CR47","doi-asserted-by":"publisher","first-page":"5107","DOI":"10.2147\/OTT.S145613","volume":"10","author":"M Ichiki","year":"2017","unstructured":"Ichiki M, Wataya H, Yamada K, Tsuruta N, Takeoka H, Okayama Y, et al. Preventive effect of kampo medicine (hangeshashin-to, TJ-14) plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer. Onco Targets Ther. 2017;10:5107\u201313.","journal-title":"Onco Targets Ther"},{"issue":"2","key":"5039_CR48","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1248\/bpb.b24-00602","volume":"48","author":"Y Noguchi","year":"2025","unstructured":"Noguchi Y, Inose R, Ohtsubo T, Kobayashi D, Kato Y, Muraki Y, et al. Effect of Severe Neutropenia Caused by S-1 Adjuvant Chemotherapy on Pancreatic Cancer Prognosis. Biol Pharm Bull. 2025;48(2):132\u20136.","journal-title":"Biol Pharm Bull"},{"issue":"1","key":"5039_CR49","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12885-020-06797-2","volume":"20","author":"K Sano","year":"2020","unstructured":"Sano K, Nakadate K, Hanada K. Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer. BMC Cancer. 2020;20(1):279.","journal-title":"BMC Cancer"},{"issue":"2","key":"5039_CR50","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.explore.2023.08.003","volume":"20","author":"X Lin","year":"2024","unstructured":"Lin X, Fang Y, Cheng Y, Wang Q. Chinese herbal medicine for irinotecan-induced diarrhea: A systematic review and meta-analysis. Explore (NY). 2024;20(2):158\u201367.","journal-title":"Explore (NY)"},{"key":"5039_CR51","doi-asserted-by":"publisher","first-page":"115858","DOI":"10.1016\/j.jep.2022.115858","volume":"302","author":"C Kong","year":"2023","unstructured":"Kong C, Pang X, Su Z, Liu Y. Botany, ethnopharmacology, phytochemistry and pharmacology of Erodii Herba Geranii Herba-An review. J Ethnopharmacol. 2023;302:115858. (Pt A).","journal-title":"J Ethnopharmacol"},{"issue":"14","key":"5039_CR52","first-page":"3723","volume":"47","author":"LN Gao","year":"2022","unstructured":"Gao LN, Li RC, Zhou CZ, Liu QZ, Wan XH. [Chemical constituents and pharmacological effects of Dictamni Cortex: a review]. Zhongguo Zhong Yao Za Zhi. 2022;47(14):3723\u201337.","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"5039_CR53","doi-asserted-by":"publisher","first-page":"113688","DOI":"10.1016\/j.jep.2020.113688","volume":"269","author":"D Ren","year":"2021","unstructured":"Ren D, Shen ZY, Qin LP, Zhu B. Pharmacology, phytochemistry, and traditional uses of Scrophularia ningpoensis Hemsl. J Ethnopharmacol. 2021;269:113688.","journal-title":"J Ethnopharmacol"},{"key":"5039_CR54","doi-asserted-by":"publisher","first-page":"156759","DOI":"10.1016\/j.cyto.2024.156759","volume":"184","author":"L Yan","year":"2024","unstructured":"Yan L, Li J, Yang Y, Zhang X, Zhang C. Old drug, new use: Recent advances for G-CSF. Cytokine. 2024;184:156759.","journal-title":"Cytokine"},{"issue":"6","key":"5039_CR55","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1093\/aje\/kwk052","volume":"165","author":"E Vittinghoff","year":"2007","unstructured":"Vittinghoff E, McCulloch CE. Relaxing the Rule of Ten Events per Variable in Logistic and Cox Regression. Am J Epidemiol. 2007;165(6):710\u20138.","journal-title":"Am J Epidemiol"},{"key":"5039_CR56","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.jclinepi.2016.02.031","volume":"76","author":"EO Ogundimu","year":"2016","unstructured":"Ogundimu EO, Altman DG, Collins GS. Adequate sample size for developing prediction models is not simply related to events per variable. J Clin Epidemiol. 2016;76:175\u201382.","journal-title":"J Clin Epidemiol"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-05039-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05039-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05039-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:22:23Z","timestamp":1781648543000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-026-05039-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,19]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5039"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-05039-4","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,19]]},"assertion":[{"value":"23 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University, and the procedures used in this study adhere to the Declaration of Helsinki. The need for individual consent was waived by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University because of the retrospective nature of the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"824"}}