Itraconazole in Non Small Cell Lung Cancer

Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer. Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer. Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015). Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Stage IV NSCLC patients who have not received chemotherapy for metastatic disease management yet or inoperable locally recurrent Stage III NSCLC after concurrent chemoradiotherapy.
2. ECOG 0-2.
3. Age \>18 years.
4. Adequate bone marrow reserve (white blood cells \[WBC\] ≥ 3.5 × 109 /L, neutrophils ≥ 1.5 × 109 /L, platelets ≥ 100 × 109 /L, and hemoglobin ≥ 9.0 gm/dL).

Exclusion Criteria:

1. Inadequate liver function (bilirubin \> 1.5 times upper normal limit \[ULN\] and alanine transaminase \[ALT\] or aspartate transaminase \[AST\] \> 3.0 ULN or up to 5.0 UNL in the presence of hepatic metastases).
2. Inadequate renal function (creatinine \> 1.25 times ULN, creatinine clearance \< 50mL/min).
3. Serious comorbid systemic disorder incompatible with the study.
4. Presence of other primary malignancy.
5. Patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
6. Patients with hypersensitivity to Itraconazole.
7. Patients receiving any Cytochrome P450 (CYP 3A4) inhibitor as clarithromycin, diltiazem, verapamil, quinidine ….etc.
8. Pregnant female patients.

• DERIVEDMohamed AW, Elbassiouny M, Elkhodary DA, Shawki MA, Saad AS. 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. Med Oncol. 2021 Feb 9;38(3):23. doi: 10.1007/s12032-021-01475-0. PMID 33559053