# A Novel Approach to Reducing Chemoresistance in Advanced Ovarian Cancer: The Effect of Itraconazole—A Single-Institution Randomized Placebo-Controlled Trial

## TL;DR

This study found that adding itraconazole to standard chemotherapy improved outcomes and quality of life in advanced ovarian cancer patients.

## Contribution

A clinical trial demonstrating itraconazole's potential to reduce chemoresistance and improve survival in ovarian cancer.

## Key findings

- Itraconazole improved tumor response rates and progression-free survival in ovarian cancer patients.
- It reduced CA-125 and P-glycoprotein levels while increasing VEGFR-2 levels.
- Quality of life improved with fewer side effects in patients receiving itraconazole.

## Abstract

This randomized, placebo-controlled double-blind clinical trial evaluated itraconazole as an adjunct to standard paclitaxel–carboplatin chemotherapy in 60 patients with advanced epithelial ovarian cancer. Participants were divided into two groups: one received standard chemotherapy plus placebo, and the other received chemotherapy plus 400 mg itraconazole for five days per cycle. The itraconazole group showed significantly improved overall and disease control response rates, progression-free survival, and a reduction in serum CA-125 and P-glycoprotein levels, with increased VEGFR-2 levels as compared to the control group. The quality of life was markedly improved across physical, emotional, and social domains, with fewer chemotherapy-related side effects. Importantly, itraconazole was well-tolerated and did not increase hematologic or systemic toxicities. These findings suggest that itraconazole may enhance tumor response, mitigate chemoresistance, and improve quality of life in patients with advanced ovarian cancer, supporting its potential as a safe, cost-effective adjunctive therapy; however, these findings require further validation.

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-naïve patients with advanced ovarian epithelial cancer. Method: This randomized placebo-controlled double-blind study involved 60 chemotherapy-naïve 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.