Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer
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. This prospective, randomized double blind placebo-controlled study enrol...
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| Veröffentlicht in: | Life sciences (1973) 2022-06, Vol.299, p.120536-120536, Article 120536 |
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| container_title | Life sciences (1973) |
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| creator | Hegazy, Sahar K. El-Azab, Gamal A. Zakaria, Fatma Mostafa, Mohamed F. El-Ghoneimy, Reham A. |
| description | 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.
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 |
| doi_str_mv | 10.1016/j.lfs.2022.120536 |
| format | Article |
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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.
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).
Mebendazole may represent an attractive candidate for drug repositioning against mCRC secondary to its safety and efficacy in enhancing tumor response to chemotherapy.
NCT03925662, retrospectively.
•Our study aimed at investigating the anti-tumor activity and safety of mebendazole in metastatic colorectal cancer patients.•Mebendazole enhanced tumor response to treatment producing significant improvement of overall response rate after 12 weeks.•Mebendazole produced significant decline of VEGF level 12 weeks after treatment and significant elevation in PFS.•Mebendazole represents an attractive and well- tolerated candidate for drug repurposing against metastatic colorectal cancer.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2022.120536</identifier><identifier>PMID: 35385794</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Antibodies, Monoclonal, Humanized ; Anticancer properties ; Antigens ; Antineoplastic Combined Chemotherapy Protocols ; Antiparasitic agents ; Antitumor agents ; Bevacizumab ; Bevacizumab - pharmacology ; Bevacizumab - therapeutic use ; Cancer ; Carcinoembryonic Antigen ; Chemotherapy ; Colonic Neoplasms - drug therapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - pathology ; Computed tomography ; Drug Repositioning ; Fluorouracil ; FOLFOX4 & bevacizumab ; Growth factors ; Humans ; Mebendazole ; Mebendazole - pharmacology ; Mebendazole - therapeutic use ; Metastases ; Metastatic colorectal cancer ; Patients ; Placebos ; Progression free survival ; Prospective Studies ; Retrospective Studies ; Safety ; Serum levels ; Statistical analysis ; Survival ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A</subject><ispartof>Life sciences (1973), 2022-06, Vol.299, p.120536-120536, Article 120536</ispartof><rights>2022 Elsevier Inc.</rights><rights>Copyright © 2022 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Jun 15, 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-c0d2439b11794f397ae063eb8927be1254245b4f787808cf3420c631e58f0dfa3</citedby><cites>FETCH-LOGICAL-c381t-c0d2439b11794f397ae063eb8927be1254245b4f787808cf3420c631e58f0dfa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2022.120536$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35385794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hegazy, Sahar K.</creatorcontrib><creatorcontrib>El-Azab, Gamal A.</creatorcontrib><creatorcontrib>Zakaria, Fatma</creatorcontrib><creatorcontrib>Mostafa, Mohamed F.</creatorcontrib><creatorcontrib>El-Ghoneimy, Reham A.</creatorcontrib><title>Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>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.
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.
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).
Mebendazole may represent an attractive candidate for drug repositioning against mCRC secondary to its safety and efficacy in enhancing tumor response to chemotherapy.
NCT03925662, retrospectively.
•Our study aimed at investigating the anti-tumor activity and safety of mebendazole in metastatic colorectal cancer patients.•Mebendazole enhanced tumor response to treatment producing significant improvement of overall response rate after 12 weeks.•Mebendazole produced significant decline of VEGF level 12 weeks after treatment and significant elevation in PFS.•Mebendazole represents an attractive and well- tolerated candidate for drug repurposing against metastatic colorectal cancer.</description><subject>Antibodies, Monoclonal, Humanized</subject><subject>Anticancer properties</subject><subject>Antigens</subject><subject>Antineoplastic Combined Chemotherapy Protocols</subject><subject>Antiparasitic agents</subject><subject>Antitumor agents</subject><subject>Bevacizumab</subject><subject>Bevacizumab - pharmacology</subject><subject>Bevacizumab - therapeutic use</subject><subject>Cancer</subject><subject>Carcinoembryonic Antigen</subject><subject>Chemotherapy</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Computed tomography</subject><subject>Drug Repositioning</subject><subject>Fluorouracil</subject><subject>FOLFOX4 & bevacizumab</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Mebendazole</subject><subject>Mebendazole - pharmacology</subject><subject>Mebendazole - therapeutic use</subject><subject>Metastases</subject><subject>Metastatic colorectal cancer</subject><subject>Patients</subject><subject>Placebos</subject><subject>Progression free survival</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Safety</subject><subject>Serum levels</subject><subject>Statistical analysis</subject><subject>Survival</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9P3DAQxa0KVLa0H6CXyhKXXrL4TxI74lShUiqBemnPlmOPkZdsnNoJEv30zBLooYdKluYwvxm_eY-Qj5xtOePt-W47hLIVTIgtF6yR7Ruy4Vp1FWslPyIbxkRdSeyckHel7BhjTaPkW3IiG6kb1dUbcn8LPYze_kkDXNCQ057aEd8cq8lmW-IcHfV5uaNzopZOCMQSxzvq7OijtzPQkPJKZJiWPKXndhypS0PK4GY7HGAH-T05DnYo8OGlnpJfV19_Xl5XNz--fb_8clM5qflcOeZFLbuec1QYZKcs4D3Q606oHrhoalE3fR2UVpppF2QtmMODodGB-WDlKfm87kW1vxcos0HNDobBjpCWYkRba9a2rZSInv2D7tKSR1SHlOKK4R8CKb5SLqdSMgQz5bi3-dFwZg5JmJ3BJMwhCbMmgTOfXjYv_R7834lX6xG4WAFAKx4iZFNcBPTJx4Nrxqf4n_VPq7GYXg</recordid><startdate>20220615</startdate><enddate>20220615</enddate><creator>Hegazy, Sahar K.</creator><creator>El-Azab, Gamal A.</creator><creator>Zakaria, Fatma</creator><creator>Mostafa, Mohamed F.</creator><creator>El-Ghoneimy, Reham A.</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20220615</creationdate><title>Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer</title><author>Hegazy, Sahar K. ; El-Azab, Gamal A. ; Zakaria, Fatma ; Mostafa, Mohamed F. ; El-Ghoneimy, Reham A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-c0d2439b11794f397ae063eb8927be1254245b4f787808cf3420c631e58f0dfa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies, Monoclonal, Humanized</topic><topic>Anticancer properties</topic><topic>Antigens</topic><topic>Antineoplastic Combined Chemotherapy Protocols</topic><topic>Antiparasitic agents</topic><topic>Antitumor agents</topic><topic>Bevacizumab</topic><topic>Bevacizumab - pharmacology</topic><topic>Bevacizumab - therapeutic use</topic><topic>Cancer</topic><topic>Carcinoembryonic Antigen</topic><topic>Chemotherapy</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Computed tomography</topic><topic>Drug Repositioning</topic><topic>Fluorouracil</topic><topic>FOLFOX4 & bevacizumab</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Mebendazole</topic><topic>Mebendazole - pharmacology</topic><topic>Mebendazole - therapeutic use</topic><topic>Metastases</topic><topic>Metastatic colorectal cancer</topic><topic>Patients</topic><topic>Placebos</topic><topic>Progression free survival</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Safety</topic><topic>Serum levels</topic><topic>Statistical analysis</topic><topic>Survival</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hegazy, Sahar K.</creatorcontrib><creatorcontrib>El-Azab, Gamal A.</creatorcontrib><creatorcontrib>Zakaria, Fatma</creatorcontrib><creatorcontrib>Mostafa, Mohamed F.</creatorcontrib><creatorcontrib>El-Ghoneimy, Reham A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hegazy, Sahar K.</au><au>El-Azab, Gamal A.</au><au>Zakaria, Fatma</au><au>Mostafa, Mohamed F.</au><au>El-Ghoneimy, Reham A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2022-06-15</date><risdate>2022</risdate><volume>299</volume><spage>120536</spage><epage>120536</epage><pages>120536-120536</pages><artnum>120536</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>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.
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.
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).
Mebendazole may represent an attractive candidate for drug repositioning against mCRC secondary to its safety and efficacy in enhancing tumor response to chemotherapy.
NCT03925662, retrospectively.
•Our study aimed at investigating the anti-tumor activity and safety of mebendazole in metastatic colorectal cancer patients.•Mebendazole enhanced tumor response to treatment producing significant improvement of overall response rate after 12 weeks.•Mebendazole produced significant decline of VEGF level 12 weeks after treatment and significant elevation in PFS.•Mebendazole represents an attractive and well- tolerated candidate for drug repurposing against metastatic colorectal cancer.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>35385794</pmid><doi>10.1016/j.lfs.2022.120536</doi><tpages>1</tpages></addata></record> |
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| subjects | Antibodies, Monoclonal, Humanized Anticancer properties Antigens Antineoplastic Combined Chemotherapy Protocols Antiparasitic agents Antitumor agents Bevacizumab Bevacizumab - pharmacology Bevacizumab - therapeutic use Cancer Carcinoembryonic Antigen Chemotherapy Colonic Neoplasms - drug therapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - pathology Computed tomography Drug Repositioning Fluorouracil FOLFOX4 & bevacizumab Growth factors Humans Mebendazole Mebendazole - pharmacology Mebendazole - therapeutic use Metastases Metastatic colorectal cancer Patients Placebos Progression free survival Prospective Studies Retrospective Studies Safety Serum levels Statistical analysis Survival Tumors Vascular endothelial growth factor Vascular Endothelial Growth Factor A |
| title | Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer |
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