{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:39:27Z","timestamp":1777894767542,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: The five-year survival rate of patients with ovarian cancer remains less than 50%, secondary to chemotherapy resistance. Purpose: This study aims to evaluate the effects of itraconazole as a supplementary treatment with paclitaxel and carboplatin on malignancy response and in preventing the initial development of chemoresistance in chemotherapy-na\u00efve patients with advanced ovarian epithelial cancer. Method: This randomized placebo-controlled double-blind study involved 60 chemotherapy-na\u00efve patients with advanced epithelial ovarian malignancy who were randomized into two arms; the placebo and itraconazole groups. The placebo group received six chemotherapy cycles and four inactive capsules, while the itraconazole group received six chemotherapy cycles and 400 mg oral itraconazole for five days per cycle. Results: Following completion of six chemotherapy cycles and when contrasted with the control arm, the itraconazole arm demonstrated statistically significant improvements in tumor response. The objective response rate was 80% in the itraconazole group compared with 47% in the placebo group (p = 0.015), while the disease control rate was 100% versus 80%, respectively (p = 0.023). The median progression-free survival (PFS), defined as the time point at which 50% of patients experienced disease progression or death, was 13.5 months for the overall study population. PFS was evaluated as a fixed-time endpoint at 18 months following completion of chemotherapy for the overall study population. Progression-free survival was significantly improved in the itraconazole group, with 70% of patients remaining progression-free compared with 26.7% in the placebo group (p = 0.001). Also, the itraconazole group produced significant declines in the serum levels of CA-125 (p = 0.005) and p-glycoprotein (p = 0.042) with significant elevation in VEGFR-2 (p = 0.006) as compared to the control group. Itraconazole was safe and its use was associated with a significant improvement in the quality of life (QOL). Conclusions: Itraconazole could represent a promising add-on therapy to enhance tumor response to chemotherapy in patients with ovarian cancer.<\/jats:p>","DOI":"10.3390\/curroncol33010021","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:33:25Z","timestamp":1767191605000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Approach to Reducing Chemoresistance in Advanced Ovarian Cancer: The Effect of Itraconazole\u2014A Single-Institution Randomized Placebo-Controlled Trial"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5818-7840","authenticated-orcid":false,"given":"Ahmed E. S.","family":"Besheir","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta 31511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-7315","authenticated-orcid":false,"given":"Sahar M.","family":"El-Hagar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta 31511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5800-2354","authenticated-orcid":false,"given":"Hesham A.","family":"Tawfik","sequence":"additional","affiliation":[{"name":"Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-5416","authenticated-orcid":false,"given":"Tarek M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta 31511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00262-024-03708-3","article-title":"The biological roles of CD47 in ovarian cancer progression","volume":"73","author":"Xing","year":"2024","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cordani, N., Bianchi, T., Ammoni, L.C., Cortinovis, D.L., Cazzaniga, M.E., Lissoni, A.A., Landoni, F., and Canova, S. (2023). An overview of PARP resistance in ovarian cancer from a molecular and clinical perspective. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511890"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1097\/AOG.0000000000004173","article-title":"Updates and new options in advanced epithelial ovarian cancer treatment","volume":"137","author":"Kurnit","year":"2021","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3892\/or.2022.8293","article-title":"Molecular mechanisms of platinum-based chemotherapy resistance in ovarian cancer","volume":"47","author":"Yang","year":"2022","journal-title":"Oncol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/cncr.34023","article-title":"Improving the quality of care for patients with advanced epithelial ovarian cancer: Program components, implementation barriers, and recommendations","volume":"128","author":"Temkin","year":"2022","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113616","DOI":"10.1016\/j.biopha.2022.113616","article-title":"Repurposed itraconazole for use in the treatment of malignancies as a promising therapeutic strategy","volume":"154","author":"Li","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12032-021-01475-0","article-title":"The effect of itraconazole on the clinical outcomes of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: A randomized controlled study","volume":"38","author":"Mohamed","year":"2021","journal-title":"Med. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6552","DOI":"10.1038\/s41598-017-06510-7","article-title":"The anti-cancer effects of itraconazole in epithelial ovarian cancer","volume":"7","author":"Choi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_10","first-page":"2007","article-title":"Impact of Combination Chemotherapy with Itraconazole on Survival for Patients with Recurrent or Persistent Ovarian Clear Cell Carcinoma","volume":"34","author":"Tsubamoto","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s00404-021-06020-y","article-title":"Response evaluation after neoadjuvant therapy: Evaluation of chemotherapy response score and serological and\/or radiological assessment of response in ovarian cancer patients","volume":"304","author":"Ramspott","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.5306\/wjco.v11.i2.53","article-title":"Objective response rate assessment in oncology: Current situation and future expectations","volume":"11","author":"Aykan","year":"2020","journal-title":"World J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1179299x19860815","DOI":"10.1177\/1179299X19860815","article-title":"Chemotherapy Resistance in Advanced Ovarian Cancer Patients","volume":"11","author":"Pokhriyal","year":"2019","journal-title":"Biomark. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/JTO.0b013e31828c3950","article-title":"Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non\u2013small-cell lung cancer","volume":"8","author":"Rudin","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Matsas, A., Stefanoudakis, D., Troupis, T., Kontzoglou, K., Eleftheriades, M., Christopoulos, P., Panoskaltsis, T., Stamoula, E., and Iliopoulos, D.C. (2023). Tumor markers and their diagnostic significance in ovarian cancer. Life, 13.","DOI":"10.3390\/life13081689"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13048-019-0503-7","article-title":"Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review","volume":"12","author":"Dochez","year":"2019","journal-title":"J. Ovarian Res."},{"key":"ref_17","first-page":"2079654","article-title":"Repurposing Drugs in Controlling Recurrent Platinum-Resistant Clear-Cell Ovarian Cancer","volume":"2023","author":"Sinsuwan","year":"2023","journal-title":"Case Rep. Oncol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Villegas-Vazquez, E.Y., Mar\u00edn-Carrasco, F.P., Reyes-Hern\u00e1ndez, O.D., B\u00e1ez-Gonz\u00e1lez, A.S., Bustamante-Montes, L.P., Padilla-Benavides, T., Quintas-Granados, L.I., and Figueroa-Gonz\u00e1lez, G. (2025). Revolutionizing ovarian cancer therapy by drug repositioning for accelerated and cost-effective treatments. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1514120"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ceci, C., Atzori, M.G., Lacal, P.M., and Graziani, G. (2020). Role of VEGFs\/VEGFR-1 signaling and its inhibition in modulating tumor invasion: Experimental evidence in different metastatic cancer models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041388"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sopo, M., Anttila, M., H\u00e4m\u00e4l\u00e4inen, K., Kivel\u00e4, A., Yl\u00e4-Herttuala, S., Kosma, V.-M., Keski-Nisula, L., and Sallinen, H. (2019). Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5757-3"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188888","DOI":"10.1016\/j.bbcan.2023.188888","article-title":"Neo-vascularization-based therapeutic perspectives in advanced ovarian cancer","volume":"1878","author":"Bhardwaj","year":"2023","journal-title":"Biochim. Biophys. Acta (BBA) Rev. Cancer"},{"key":"ref_22","first-page":"1666","article-title":"miRNA-195 suppresses cell proliferation of ovarian cancer cell by regulating VEGFR2 and AKT signaling pathways","volume":"18","author":"Chen","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_23","unstructured":"Sosnik, A., and Bendayan, R. (2019). Drug Efflux Pumps in Cancer Resistance Pathways: From Molecular Recognition and Characterization to Possible Inhibition Strategies in Chemotherapy, Academic Press."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.2147\/OTT.S193433","article-title":"Mitochondria P-glycoprotein confers paclitaxel resistance on ovarian cancer cells","volume":"12","author":"Guo","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_25","first-page":"2481","article-title":"Impact of Combination Chemotherapy with Itraconazole on Survival of Patients with Refractory Ovarian Cancer","volume":"34","author":"Tsubamoto","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.2147\/IDR.S170706","article-title":"Trough concentration of itraconazole and its relationship with efficacy and safety: A systematic review and meta-analysis","volume":"11","author":"Zhang","year":"2018","journal-title":"Infect. Drug Resist."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/1\/21\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:02:57Z","timestamp":1767193377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/1\/21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,31]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["curroncol33010021"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33010021","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,31]]}}}