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

Abstract

Itraconazole is an oral antifungal that has a been reported to have anticancer effect in non-small cell lung cancer (NSCLC) through inhibition of angiogenesis. The aim is to evaluate the effect of using itraconazole on the clinical outcome of metastatic NSCLC. This was a prospective randomized controlled open-label study conducted on 60 chemotherapy-naive metastatic NSCLC. Patients were simply randomized to either Control group who received platinum-based chemotherapy for a maximum of six cycles or Itraconazole group who received the same chemotherapy regimen in addition to itraconazole 200 mg daily for 21 days starting from day 1 in each cycle. Primary outcome was 1-year progression-free survival (PFS) while secondary outcomes included overall response rate (ORR), 1-year overall survival (OS) and tolerability. The two groups were comparable at baseline with no significant difference between groups regarding demographics and clinical characteristics. The ORR in Control group was 66.7% versus 90% in Itraconazole group (p value 0.028). There was a significant difference between groups regarding PFS where the mean 1-year PFS was 5.415 months in Control group versus 6.556 months in Itraconazole group (p value = 0.002). However, there was no significant difference between groups with respect to 1-year OS. All adverse effects reported were tolerable except for one patient who developed grade 2 cardiotoxicity in Itraconazole group requiring itraconazole discontinuation. Itraconazole use was beneficial in NSCLC in terms of 1-year PFS and ORR which was not reflected by improvement in 1-year OS. Clinical trial.gov registration number: NCT03664115, date of registration:

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

“…Itraconazole was evaluated under randomized open-label placebo-controlled trial including chemo naïve advanced NSCLC patients treated with platinum-based chemo plus itraconazole regularly for 21 days or placebo. There was significant ORR, and PFS among groups but no difference in 1-year OS [31]. Anti-bacterial medications such as minocycline and doxycycline were found to be inhibit metalloproteinase and vascular endothelial growth factor (VEGF) reducing angiogenesis and degradation of extracellular matrix (ECM) [32, 33, 34].…”

Itraconazole inhibits tumor growth via CEBPB‐mediated glycolysis in colorectal cancer

“…Large studies have revealed that itraconazole in combination with other current agents made cancer patients benefit from oncotherapy in laboratory and clinical trials 4,49,50 . For example, combination chemotherapy with gemcitabine, nab‐paclitaxel, oxaliplatin and itraconazole (GnPO‐ITC) regimen showed promising efficacy with manageable toxicities for controlling disease progression and improving OS in pancreatic cancer patients 51 .…”

Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances

“…In a phase 2 trial involving metastatic nonsquamous NSCLC, itraconazole combined with pemetrexed significantly prolonged the overall survival outcomes for patients by up to 32 months, compared to pemetrexed alone (8 months) (112). In a randomized controlled study investigating the effects of itraconazole on clinical outcomes in patients with advanced NSCLC receiving platinum-based chemotherapy, it was confirmed that itraconazole significantly improved 1-year PFS and overall response rates (ORR), but not 1year OS (113). The rationale for these two studies was based on anti-angiogenic effects of itraconazole.…”