Which preclinical dose regimens of ivermectin produced anti‑tumor effects and how do those compare to approved human antiparasitic dosing?
Executive summary
Preclinical oncology studies report that ivermectin produces anti‑tumor effects across many models, most commonly using mouse doses with a median of ~5 mg/kg (range ~2.4–40 mg/kg) given over multi‑day courses and by several routes, which translate to human equivalent doses roughly around 0.4 mg/kg — higher and/or more frequent exposure than typical antiparasitic regimens of 150–200 μg/kg single doses (0.15–0.20 mg/kg) [1] [2] [3]. The experimental regimens often involved repeated dosing for 10–42 days or daily schedules that have not been validated for safety or efficacy in large human trials, leaving a substantive translational gap between promising animal results and clinical practice [1] [2] [4].
1. What preclinical regimens produced anti‑tumor effects — dose ranges and timing
Across reviews and original reports, murine xenograft and syngeneic studies most commonly used ivermectin doses from about 2.4–40 mg/kg, with the median reported at ~5 mg/kg, and treatment durations spanning roughly 10–42 days delivered orally, intraperitoneally or intratumorally; those regimens have been associated with >50% reductions in tumor volume in multiple models [1] [2] [5]. Specific experiments that induced tumor growth delay include oral gavage at 3 mg/kg given over 8–10 doses which delayed growth of leukemia xenografts, and other reports of 3–5 mg/kg suppressing melanoma and diverse xenografts without overt toxicity in mice [6] [7]. Not all studies used identical schedules: some reported continuous or repeated exposures beginning when tumors were palpable (daily for ~8–10 doses) while others tested intraperitoneal or intratumoral delivery across weeks; one osteosarcoma report used 0.5 mg/kg and still observed significant tumor reduction, highlighting model‑dependent sensitivity [6] [8] [1].
2. How those animal doses translate to human equivalents
Investigators applying standard body‑surface‑area conversions calculate that a 5 mg/kg mouse dose approximates a human equivalent dose (HED) near 0.4 mg/kg; several reviews explicitly make that conversion and note the HED sits above typical antiparasitic exposures but below some high‑dose human safety evaluations referenced in the literature [1] [2]. Practical implications are that an anticancer exposure extrapolated from many preclinical regimens would require repeated human dosing well above the single‑dose parasitic standard (0.15–0.20 mg/kg), often moving into the 0.3–0.5 mg/kg range or higher depending on regimen and model [2] [3].
3. Comparison to approved antiparasitic dosing and human safety data
Standard approved human antiparasitic doses are typically in the 150–200 μg/kg (0.15–0.20 mg/kg) range given as single or limited doses for infections, whereas the preclinical anticancer regimens either require higher per‑kg exposures, more frequent administration, or prolonged multi‑day courses to reproduce tumor effects seen in animals [3] [2]. Some clinical reports and small dose‑finding studies have explored substantially higher or repeated dosing and indicate tolerability in limited cohorts, but these human data are sparse, heterogeneous, and insufficient to prove safety or efficacy for cancer indications — a gap repeatedly emphasized in reviews [2] [4].
4. Caveats, heterogeneity of evidence, and misinformation risks
Preclinical signals are mechanistically diverse — apoptosis, mitochondrial dysfunction, inhibition of stem‑like cells and modulation of signaling pathways — and efficacy varies by tumor type, route, and schedule, so no single preclinical “anticancer dose” exists; convergence around 3–5 mg/kg in mice is common but not universal, and isolated reports of efficacy at lower doses (0.5 mg/kg) complicate a simple translation [9] [7] [8]. Critics and clinicians warn that social media has amplified preliminary lab findings into off‑label use, risking toxicity and delay of proven therapies; authoritative reviews call for rigorously designed clinical trials rather than ad hoc dosing extrapolations [10] [4].
5. Bottom line for translational prospects
The preclinical literature documents reproducible anti‑tumor activity across models using repeated ivermectin regimens (median ~5 mg/kg in mice) that correspond to human equivalent exposures higher than standard antiparasitic single doses; however, clinical adoption requires controlled phase 1/2 trials to define safe, effective schedules and to close the translational gap that current evidence leaves open [1] [2] [4].