Effect of Cholera Vaccine on different Cancer types.
Dukoral is generally used to treat the Cholera. Sweden study of Cholera vaccines against different types of cancer shown that it is effective for different kinds of cancer. Please see this article Association between post-diagnostic use of cholera vaccine and risk of death in prostate cancer patients.
Dukoral® is approved for use in 60 countries, including Canada where it is available without a prescription for prevention of travelers’ diarrhea. The side effects of Dukoral® are minimal and rare. They include temporary loss of appetite, headache, and joint pain. There is a long track record of its use, with approval in Sweden for travelers to endemic cholera regions of the world since 1991. It is approved for ages 2 and up. Dukoral® may be one of the most non-toxic repurposed agents in all of oncology.
Dukoral® is made from heat-killed whole Vibrio cholerae,with the addition of recombinant cholera toxin B (rCTB) as an adjuvant. When comparing this vaccine against the other three vaccines used worldwide, only Dukoral® contains rCTB that has an immune-modulating effect. The rCTB has been used as a model molecule to study immune modulation, with both immune suppressive and immune augmenting effects, depending on context. The presence of rCTB is a key distinction from the other OCVs. Antibodies to rCTB cross react with heat labile enterotoxin, the toxin that causes diarrhea from enterotoxigenic Escherichia coli (ETEC) infection. ETEC is responsible for up to 50% of all cases of travelers’ diarrhea.
Colorectal Cancer (CRC)
In 2018 Dr. Jianguang Ji and colleagues published the first of a series of three papers.5 Using the Swedish Cancer Register and the Swedish Prescribed Drug Register, they extracted data to determine whether prescription of OCV (Dukoral®) was associated with mortality. There were 175 patients diagnosed with CRC between 2005-2012 who were also prescribed OCV at some point after their diagnosis. When these patients were compared to matched controls, there was a 47% decreased risk of death from CRC. Use of Dukoral® was also associated with a 41% drop in risk of death from any cause. These decreases were observed regardless of sex, tumor stage at diagnosis (mostly stages II/III), or patient age.
Later that year the same group, led by Dr. Ji, published similar results for men who had taken Dukoral® after a diagnosis of prostate cancer.6 The 841 patients who had taken Dukoral® were compared to the entire database of men diagnosed with prostate cancer in Sweden between 2004-2014 (n=89,142). Ji’s group reported that there was a 43% decrease in prostate cancer-related deaths and a 47% decrease in overall deaths compared to men who had not received Dukoral®. The average time from cancer diagnosis to vaccination was just over two years (27 months). They were followed for nearly five years (58.9 months) on average.
An intriguing finding that was only noticed in the prostate cancer data was that the associated decrease in deaths changed over time. The reduction in deaths increased for the first 15 months, so that risk of death decreased as much as 80% in certain subsets of men (e.g., lower income subgroup). Then the trend reversed with less reduction over the subsequent months of the study. If the curve rendered by this data is extrapolated further than 60 months, then the 43% reduction in overall mortality would be expected to erode over time. This implies that any benefit, assuming it is due to the Dukoral®, may not be permanent and wears off.
The latest study from Ji and colleagues, published in 2020, looked at 603 patients with a history of breast cancer and compared them to 1194 women who were matched by demographic, socioeconomic, and non-cancer-related clinical factors.7 The time between diagnosis and Dukoral® prescription ranged from 15-51 months (median 30 months). Follow-up time ranged from 47-85 months (median 62 months). The women who were prescribed Dukoral® were 47% less likely to have died due to breast cancer and 46% less likely to have died of any cause when compared their unvaccinated counterparts.
The results from these three studies are remarkable. They are more impressive than much of the outcome data on FDA-approved drugs for each of these cancers. That said, we are not sure whether Dukoral® use is cause or coincidence since these studies are all based on retrospective observational data.
There are a few other caveats that should be mentioned. One is that all of these data are from one country, Sweden (>90% Swedes in each study). While linking information in several Swedish health registries made data collection possible, a population-based study in one country limits the applicability of the results to more diverse populations. As mentioned, the OCV used was exclusively one brand, Dukoral®, which was made by a Swedish company, all three of these studies were done by the same group led by Dr. Ji. If a separate group were to add to these three studies and find repeatable results, this would go a long way to validate the findings.
The results shown above are impressive, the mechanism so plausible, and the risk of side effects so low that according to me it should be recommended for the above described cancers. There is little reason not to encourage patients with a history of colorectal, breast, or prostate cancer to take Dukoral®
It should be mentioned that the cancers that were shown to have reduced risk of death with Dukoral®–CRC, prostate and breast cancers—all share a similar histology. They are all adenocarcinomas. Would these correlations be seen in other adenocarcinomas—those that arise in the lung? the ovaries? the pancreas? Would cancers that arise from squamous cells
, connective tissue or the lymph system have similar trends in the data? We do not know, yet. For now, it seems that these three cancers are the ones that have the most justification for its use.
Ownership of the right to manufacture Dukoral was purchased in 2016 by the European biotechnology firm Valneva. My hope is that this company will design and fund rigorous perspective trials on whether the use of Dukoral®, or rCTB, affects the outcome of people with a history of cancer. Only a prospective trial will suffice in placing this repurposed agent on a standard of care list of things to do post-diagnosis.