Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer.

AIMS: Metastatic colorectal cancer (mCRC) predominantly contributes to cancer-related mortalities secondary to distant metastasis. This study aimed at investigating anti-tumor activity and safety of mebendazole in patients with mCRC. MATERIALS AND METHODS: This prospective, randomized double blind placebo-controlled study enrolled 40 mCRC patients who were randomized into two groups; the control group (n = 20) which received 6 cycles of bevacizumab with FOLFOX4 plus placebo tablets BID and mebendazole group (n = 20) which received 6 cycles of bevacizumab with FOLFOX4 plus mebendazole 500 mg orally BID for 12 weeks. Computed tomography scanning and serum levels of carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), liver and renal parameters were assessed at baseline and after 12 weeks. One-year overall survival and progression free survival (PFS) were also determined. Data were analyzed using paired, independent sample-t-tests, Mann-Whitney U, Chi-Square and Kaplan-Meier tests and p < 0.05 was considered statistically significant. KEY FINDINGS: Mebendazole was well tolerated and its addition to bevacizumab and FOLFOX4 enhanced tumor response to treatment which was translated by significant improvement of overall response rate 12 weeks after intervention [10 % (2) versus 65% (13) for control and mebendazole groups, respectively; p = 0.000] and significant elevation of PFS (median: 3 and 9.25 months for control and mebendazole groups, respectively; p = 0.000). Furthermore, mebendazole produced significant decline in VEGF level (p = 0.006) with non-significant variation in CEA level (p = 0.063). SIGNIFICANCE: Mebendazole may represent an attractive candidate for drug repositioning against mCRC secondary to its safety and efficacy in enhancing tumor response to chemotherapy. GOV ID: NCT03925662, retrospectively.

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study.

PURPOSE: Temozolomide (TMZ) is an oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). We reported the preliminary results of the treatment with concomitant radiation therapy (RT) plus TMZ followed by adjuvant TMZ therapy in patients with newly diagnosed high grade gliomas (HGG) to determine the safety, tolerability, and efficacy. PATIENTS AND METHODS: Between January, 2006 and December, 2007, a total of 27 patients over the age of 18 years with newly diagnosed, histologically confirmed HGG were assigned to receive oral TMZ (75 mg/m2/d x 7 d/wk for 6 weeks, from the first to the last day of RT) with fractionated RT (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by TMZ monotherapy (150 to 200 mg/m2/d x 5 days, every 28 days for six cycles) at Clinical Oncology Department, Faculty of Medicine, Tanta University Hospital. The primary end point was overall survival; secondary end points were progression-free survival, safety and tolerability. RESULTS: At a median follow-up period of 17 months (range; 5-30 months), the median progression-free survival (PFS) for all patients with HGG was 11 months, and the one-year PFS rate was 43.14%. The median overall survival (OS) was 19 months and the one-year OS rate was 81.2%. Patients with GBM were analyzed separately from HGG, and the median overall survival (OS) was 17 months, and the one-year OS rate was 83.3%. The median PFS was 10 months, and the one-year PFS rate was 27.8%. The mean age was 50.2 years (standard deviation ±9.7284), and 44.4%of patients had undergone biopsy only. There was no mortality caused by drug toxicity. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: The addition of TMZ to RT followed by adjuvant TMZ was well tolerated, and has shown promising activity in the treatment of newly diagnosed HGG. Further investigation is warranted.