{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:51:59Z","timestamp":1790189519757,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Platinum-resistant ovarian cancer (PROC) is a major therapeutic challenge, as it responds poorly to standard platinum-based treatment, has limited treatment options, and offers a generally unfavorable prognosis. Chemotherapeutic agents like pegylated liposomal doxorubicin (PLD), topotecan (TOPO), and gemcitabine (GEM) are used for this setting, but with varying efficacy and toxicity profiles, leading to an increasing need to understand the optimal balance between treatment effectiveness and tolerability for improving patient outcomes. This study evaluates the efficacy and side effects of PLD, TOPO, and GEM, focusing on progression-free survival (PFS), overall survival (OS), and safety profiles. Methods: We conducted a retrospective observational study that included 856 PROC patients treated with PLD (n = 383), TOPO (n = 352), or GEM (n = 121) at the OncoHelp Oncology Center from January 2018 to December 2023. Inclusion criteria encompass diagnosis, prior platinum therapy, and Eastern Cooperative Oncology Group (ECOG) status (0\u20132). Treatment protocols followed standard dosing, with adjustments for toxicity. Primary endpoints included PFS and OS, with safety assessed by incidence of grade 3 and 4 toxicities per CTCAE v5.0. Kaplan\u2013Meier analysis and Cox regression were used to compare survival, and statistical significance was set at p &lt; 0.05. Results: TOPO showed higher toxicity than PLD and GEM, including liver damage, hematological and non-hematological side effects, while PLD induced more skin toxicity. In terms of survival, minor differences were seen between the three chemotherapeutic agents, with a slight advantage for PLD for better disease control. Conclusions: Given the comparable results in OS across the regimens, treatment decisions should be based on other factors such as patient tolerance and quality of life.<\/jats:p>","DOI":"10.3390\/jpm15010039","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T09:11:13Z","timestamp":1737364273000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of Hepatic Function and Chemotherapy-Induced Side Effects Between Pegylated Liposomal Doxorubicin (PLD), Topotecan (TOPO), and Gemcitabine in Platinum-Resistant Ovarian Cancer (PROC)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-9160","authenticated-orcid":false,"given":"Radu-Dumitru","family":"Dragomir","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-1208","authenticated-orcid":false,"given":"Marina Adriana","family":"Mercioni","sequence":"additional","affiliation":[{"name":"Faculty of Electronics, Telecommunications and Information Technologies, Politehnica University, 300223 Timi\u0219oara, Romania"},{"name":"Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-7912","authenticated-orcid":false,"given":"\u0218erban","family":"Negru","sequence":"additional","affiliation":[{"name":"Department of Oncology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-7547","authenticated-orcid":false,"given":"Dorel","family":"Popovici","sequence":"additional","affiliation":[{"name":"Department of Oncology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1628-2359","authenticated-orcid":false,"given":"Sorin","family":"S\u0103ftescu","sequence":"additional","affiliation":[{"name":"Department of Oncology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3988-9360","authenticated-orcid":false,"given":"Andiana Roxana","family":"Blidari","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4804-661X","authenticated-orcid":false,"given":"Ioan","family":"Sas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/13543784.2021.1939305","article-title":"Advances in the treatment of platinum resistant epithelial ovarian cancer: An update on standard and experimental therapies","volume":"30","author":"Leung","year":"2021","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Havasi, A., Cainap, S.S., Havasi, A.T., and Cainap, C. (2023). Ovarian Cancer-Insights into Platinum Resistance and Overcoming It. Medicina, 59.","DOI":"10.3390\/medicina59030544"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Aldughaim, M.S., Muthana, M., Alsaffar, F., and Barker, M.D. (2020). Specific Targeting of PEGylated Liposomal Doxorubicin (Doxil\u00ae) to Tumour Cells Using a Novel TIMP3 Peptide. Molecules, 26.","DOI":"10.3390\/molecules26010100"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.critrevonc.2009.08.004","article-title":"Pegylated liposomal doxorubicin combined with carboplatin: A rational treatment choice for advanced ovarian cancer","volume":"73","author":"Pignata","year":"2010","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1517\/14656566.2.3.491","article-title":"Topoisomerase I inhibition with topotecan: Pharmacologic and clinical issues","volume":"2","author":"Arun","year":"2001","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_6","first-page":"CD005589","article-title":"Topotecan for ovarian cancer","volume":"2008","author":"Lihua","year":"2008","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00280-016-3003-0","article-title":"Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: An EORTC-PAMM perspective","volume":"78","author":"Ciccolini","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"v195","DOI":"10.1093\/annonc\/mdj980","article-title":"Gemcitabine and anthracyclines in platinum-resistant ovarian cancer","volume":"17","author":"Galligioni","year":"2006","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.semcancer.2020.08.017","article-title":"Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer","volume":"77","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_10","unstructured":"ECOG-ACRIN Cancer Research Group (2024, September 30). ECOG Performance Status. Available online: https:\/\/ecog-acrin.org\/resources\/ecog-performance-status\/."},{"key":"ref_11","unstructured":"GraphPad Software (2024, September 30). Features of GraphPad Prism. Available online: https:\/\/www.graphpad.com\/features\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1200\/JCO.2001.19.14.3312","article-title":"Recurrent epithelial ovarian carcinoma: A randomized phase III study of pegylated liposomal doxorubicin versus topotecan","volume":"19","author":"Gordon","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.2165\/00003495-199700544-00006","article-title":"Clinical Efficacy and Prospects for Use of Pegylated Liposomal Doxorubicin in the Treatment of Ovarian and Breast Cancers","volume":"54","author":"Muggia","year":"1997","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1200\/JCO.2007.13.6606","article-title":"Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer","volume":"26","author":"Ferrandina","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Xie, C., Gao, T., Yang, Y., Yang, Y., and Zhao, L. (2023). Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma\u2014An exploration of surrogate endpoint. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10613-y"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1634\/theoncologist.9-1-33","article-title":"Topotecan dosing guidelines in ovarian cancer: Reduction and management of hematologic toxicity","volume":"9","author":"Armstrong","year":"2004","journal-title":"Oncologist"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"176","DOI":"10.5468\/ogs.21308","article-title":"Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer","volume":"65","author":"Shi","year":"2022","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1634\/theoncologist.10-9-686","article-title":"Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: An integrated analysis","volume":"10","author":"Armstrong","year":"2005","journal-title":"Oncologist"},{"key":"ref_19","first-page":"1912","article-title":"Severe acute toxicity following gemcitabine administration: A report of four cases with cytidine deaminase polymorphisms evaluation","volume":"15","author":"Hryciuk","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_20","first-page":"66593","article-title":"Timing of chemotherapy-induced neutropenia: The prognostic factor in advanced pancreatic cancer patients treated with gemcitabine\/gemcitabine-based chemotherapy","volume":"8","author":"Chen","year":"2017","journal-title":"Oncologist"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.3748\/wjg.v20.i47.18001","article-title":"Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: A meta-analysis","volume":"20","author":"Liu","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Aloss, K., and Hamar, P. (2023). Recent Preclinical and Clinical Progress in Liposomal Doxorubicin. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030893"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1136\/ejhpharm-2020-002311","article-title":"Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia: A literature review of pharmaceutical and clinical aspects","volume":"28","author":"Zhu","year":"2020","journal-title":"Eur. J. Hosp. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"709","DOI":"10.2165\/00003495-199856040-00017","article-title":"Topotecan: A review of its potential in advanced ovarian cancer","volume":"56","author":"Brogden","year":"1998","journal-title":"Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/pon.5054","article-title":"Quality of life versus length of life considerations in cancer patients: A systematic literature review","volume":"28","author":"Shrestha","year":"2019","journal-title":"Psychooncology."},{"key":"ref_26","first-page":"1273","article-title":"Clinical utility of trabectedin for the treatment of ovarian cancer: Current evidence","volume":"7","author":"Mascilini","year":"2014","journal-title":"Onco Targets Ther."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/1\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:31:43Z","timestamp":1759919503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/1\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,19]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["jpm15010039"],"URL":"https:\/\/doi.org\/10.3390\/jpm15010039","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,19]]}}}