Table 2.
Clinical Evidence of Benzimidazoles for Anti-tumor Effect.
| Drug | Stage | Cancer Type | Number of Patients | Methods | Adverse Effects | Results | Identifier/Ref. |
|---|---|---|---|---|---|---|---|
| Albendazole | Phase 1 | Refractory solid tumors |
36 | Every day for 2 weeks, followed by 1 week of rest. Treatment was repeated in a 21-day cycle. 400–1200 mg b.i.d. p.o. | ABZ was well tolerated. Fatigue and mild gastrointestinal upset (Major). Myelosuppression. |
16% of patients showed a decrease in levels of tumor markers. Plasma VEGF level decreased in the first 8 h after ABZ administration. | [89] |
| Albendazole | Pilot Study | Colorectal cancer or hepatocellular carcinoma | 7 | 10 mg/kg/day, with 2 or 3 divided doses p.o. (28 d). The maximum tolerated dose was 1200 mg b.i.d. |
ABZ was well tolerated. Severe neutropenia in three patients. |
CEA decreased in two patients. CEA or α-feto protein stabilized in three patients. | [90] |
| Carbendazim | Phase 1 | Unspecified adult solid tumor | 25 | P.o weekly for 3 consecutive weeks, followed by 1 week of rest. Treatment repeated in a 28-day cycle. Determining dose. |
No results posted. | No results posted. Actual study completion date: November 2000 |
NCT00003709 |
| Mebendazole | Case report | Adrenal cancer | 1 | 100 mg b.i.d. p.o. for 19 months. | No significant adverse effects. | Metastases regressed. The patient’s disease remained stable for 19 months, but showed progression after 24 months. | [91] |
| Mebendazole | Case report | Refractory metastatic colon cancer | 1 | 100 mg b.i.d. p.o. for six weeks. | AST and ALT were increased up to > five times above the normal limit. | The metastases in the lungs and lymph nodes were near completely remissioned. A good portion of those in the liver were remissioned. | [92] |
| Mebendazole | Not applicable | Advanced hepatocellular carcinoma | 170 (recruiting) | 100 mg b.i.d. p.o. in combination with lenvatinib. | No results posted. | No results posted. Estimated study completion date: 19 June 2022 |
NCT04443049 |
| Mebendazole | Phase 1 | High-grade glioma | 24 | T.i.d. p.o. in a 28-day cycle, in combination with temozolomide. Determining dose. |
No results posted. | No results posted. Actual study completion date: 16 April 2021 |
NCT01729260 |
| Mebendazole | Phase 1 | Recurrent pediatric brain cancers | 21 (recruiting) | T.i.d. p.o. Determining dose. |
No results posted. | No results posted. Estimated study completion date: June 2022 |
NCT02644291 |
| Mebendazole | Phase 1/2 | Pediatric gliomas | 36 (recruiting) | 50–200 mg/kg/day divided twice p.o., in combination with standard anti-tumor drugs | No results posted. | No results posted. Estimated study completion date: April 2023 |
NCT01837862 |
| Mebendazole | Phase 2a | Advanced gastrointestinal cancer or cancer of unknown origin | 11 (Terminated due to lack of effect) | 50–4000 mg b.i.d. p.o. for 16 weeks. Determining dose. |
No results posted. | No results posted. Actual study completion date: 16 January 2019 |
NCT03628079 |
| Mebendazole | Phase 2 | Incurable and lethal cancers | 250 (recruiting) | Tolerable and safe doses for 10 to 12 months. Combination of two anti-protozoal drugs. |
No results posted. | No results posted. Estimated study completion date: 31 December 2023 |
NCT02366884 |
| Mebendazole | Phase 3 | Colorectal cancer | 40 (recruiting) | Folfox with avastin and MBZ. | No results posted. | No results posted. Estimated study completion date: December 2028 |
NCT03925662 |
| Mebendazole | Phase 3 | Cancer | 207 (Not yet recruiting) |
100 mg q.d. in combination with atorvastatin, metformin, and doxycycline. | No results posted. | No results posted. Estimated study completion date: 22 September 2026 |
NCT02201381 |
Abbreviations: b.i.d: twice daily; p.o.: oral administration; ABZ: albendazole; VEGF: vascular endothelial growth factor; CEA: carcinoembryonic antigen; AST: aspartate aminotransferase; ALT: alanine aminotransferase; t.i.d.: three times a day; q.d.: once daily.