ABSTRACT
In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honoured the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world's most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with the extent of IVM distributions in all 25 states with p < 0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
ABSTRACT
A French multidrug protocol for stage III ovarian cancer has achieved 77% pathologic complete response, 100% total response, and 81% actuarial 4-year survival. Our analysis indicates that these rates exceed typical with very high statistical significance. Yet neither the drugs, the combined intravenous and intraperitoneal mode of delivery, nor potential bias in the predominantly suboptimal patient population appear to explain the protocol's exceptional results. Here we propose that the atypical administration of intraperitoneal glucose prior to drugs underlies the unusual activity of this protocol. We review studies demonstrating that high-dose glucose has pronounced effects on cancer cells, most notably, substantial potentiation of certain antineoplastic agents. We consider possible mechanisms of such glucose potentiation, including hypothesized osmotic effects that would be especially strong under intraperitoneal administration. We conclude that the French ovarian cancer protocol may represent a significant advance and that glucose potentiation may be more widely applicable as an adjunct to cancer chemotherapy.
