What doses and treatment schedules of ivermectin were used in anticancer clinical studies and were they safe?
Executive summary
Clinical testing of ivermectin as an anticancer agent is nascent: small, early-phase combination trials have used oral, pulsed schedules (for example, days 1–3, 8–10, 15–17 of a 21‑day cycle) alongside immune checkpoint inhibitors, and investigators have reported these combinations to be “safe and well tolerated” in preliminary reports [1] [2]. Robust conclusions about efficacy or a definitive therapeutic dose/schedule cannot be drawn because human data remain limited and mostly phase I/II and exploratory [3] [4].
1. What clinical schedules have actually been tested so far
The clearest public description of a clinical schedule comes from an investigator-initiated phase I/II protocol testing ivermectin with checkpoint inhibitors in metastatic triple‑negative breast cancer that administered oral ivermectin on Days 1–3, 8–10 and 15–17 of each 21‑day cycle while giving balstilimab (450 mg IV) or pembrolizumab (200 mg IV) on Day 1, with treatment continued for up to roughly two years or until progression/toxicity [1]. That protocol corresponds to clinical trial registrations and abstracts indexed under NCT05318469 and the ASCO presentation describing a phase I/II study of ivermectin plus balstilimab in heavily pretreated patients [5] [2].
2. What doses have been used or proposed in human studies and safety signals
Public sources describe ivermectin dosing in oncology trials as oral pulses per cycle (days listed above) but do not universally publish a single mg/kg number for oncology cohorts in the sources provided; the trial records list the regimen structure rather than explicit per‑kg numeric doses in the snippets available [5] [1]. Outside oncology, human pharmacokinetic and safety work has escalated ivermectin to very high single doses in volunteers — studies increased doses up to 2 mg/kg in healthy volunteers without reporting serious adverse reactions, and earlier dose‑escalation work assessed tolerability of high doses in healthy adults [6] [7]. The ASCO abstract for the ivermectin + balstilimab study concluded the combination was “safe and well tolerated,” reporting an encouraging clinical benefit rate in a small, heavily pretreated population, which the authors said justified further study [2].
3. How do these clinical doses compare with preclinical anticancer concentrations
Preclinical studies often demonstrate anticancer activity at micromolar concentrations in cell lines, sometimes requiring levels above those typically achieved in human plasma after standard antiparasitic dosing; several reviews warn that many in vitro effects occur at concentrations higher than routine clinical exposure and call for formulation or delivery optimization to reach tumor‑relevant exposures [4] [8] [6]. Some groups argue that pharmacokinetic modeling and select human PK studies suggest clinically reachable concentrations could be sufficient for antitumor activity, but this remains debated and dependent on formulation, tissue penetration, and combination strategies [8] [4].
4. Safety assessment and limits of current evidence
Safety signals reported so far are encouraging but limited: phase I/II reporting describes tolerability of ivermectin when combined with immune checkpoint blockade in small cohorts, and historical high‑dose safety work in healthy volunteers found no serious reactions up to 2 mg/kg in some studies [2] [6]. However, the literature repeatedly emphasizes that clinical human data in cancer are scarce, early, and insufficient to establish a therapeutic window, optimal dose, or long‑term safety in oncology populations—especially given potential for drug–drug interactions (e.g., P‑glycoprotein effects) and the different physiology of patients with cancer [4] [9] [10].
5. Bottom line and next steps for clinicians and researchers
Current clinical use of ivermectin in oncology is experimental: pulsed, multi‑day oral schedules combined with immune therapies are being tested and preliminarily reported as tolerable, but there is no large randomized evidence of benefit and dosing remains heterogenous or incompletely reported in public summaries [1] [2] [3]. The authors of recent reviews call explicitly for rigorously designed clinical trials, optimized formulations, and safety monitoring before ivermectin can be recommended or used outside trials in cancer care [9] [4]. Given the small scale of existing clinical data, patients should be steered toward clinical trials rather than off‑label self‑administration, and investigators should publish detailed mg/kg dosing, PK, and toxicity data to move beyond preliminary safety signals [3] [2].