Evidence shows Cimetidine has a Quantifiable Impact on CRC Survival
In the past, we have reported on the potential therapeutic benefit of drugs such as Aspirin for colorectal cancer patients. The inclusion of such drugs tend to be thought of as a generally healthy way to potentially improve outcomes and reduced odds of recurrence. Toxicities associated with long term usage are usually of comparatively low-grade and thus considered a worthwhile addition to an anti-cancer regimen.
Cimetidine (Tagamet) as a Potential Anticancer Compound
A large population of studies including a number of clinical trials have been completed since the mid-1980s exploring the possible effectiveness of histamine type 2 receptor antagonists (otherwise known as H(2)Ra’s) in increasing survival or reducing rate of recurrence of colorectal cancer. H(2)Ra’s are more commonly known as the over the counter medications Cimetidine (Tagamet) and Ranitidine (Zantac).
The first study to draw interest in potential application to CRC was in 1988, where a benefit in survival was found in gastric cancers. Later, a number of studies in the early 1990s took focus on CRC directly, and results showed higher rate of survival in patients taking Cimetidine prior to, during, or after having been diagnosed with colorectal cancer. Subsequently a number of trials were completed which assessed the usage of Cimetidine in combination with standard chemotherapy regimens along with surgery.
Meta-Analysis Shows Increase in Survival
In 2012, a review of the literature was completed by Deva/Jameson, which assessed over 140 articles for meta-analysis. Upon final analysis, data included in the review were published from 1995 to 2007, including the results from six studies and 1229 patients. Throughout the data, there was a trend towards improved survival when Cimetidine was utilized as adjuvant therapy (treatment following surgery) in patients with curative intent.
Across the meta-analysis, survival and recurrence was translated to a improved Hazard Ratio, and as shown in Chart 1, the improved rate of survival varied in each of the selected studies, but overall showed a 47% improvement overall, as compared to Control, or to abstainers of Cimetidine.
Potential Links (Lymphocytes, Histamine Reduction, E-Selectin Inhibition)
Previous studies have demonstrated that Cimetidine could affect CRC patients positively for multiple reasons:
Antagonism of Histamine Type 2 Receptors
Promotion of Lymphocyte growth in general, but also more particularly near and around tumor sites as well as an improvement of immune response against the tumor,
Suppression of adhesion molecules which might favor metastasis,
Anti-angiogenetic activity – or reduction in the formation of new blood vessels.
In the last 30 years, a multitude of studies have surmised the potential link of increased survival to a few key therapeutic responses from ingestion of Cimetidine. In Lin (2004) there was a very notable increase in Lymphocytes in the blood of the patients involved where Cimetidine was taken perioperatively. In addition, there was an even more significant increase in Killer T-Cells (KTC).
From a recent study by Losurdo (2018), the role of Histamines were explored in greater detail. Their findings suggested particularly Histamine Type 2 performs a crucial role in the initiation of systemic inflammation. They noted that several prior studies had emphasized its carcinogenic effect in colorectal cancer and in this study they were able to further elucidate that HR1 and HR4 are down-regulated in colorectal cancer while HR2 is overexpressed. They concluded thusly that antagonists of HR2 are anti-carcinogenic or that they may reduce the likelihood of forming cancer in the first place.
Most Notable Survival Benefit
In Matsumoto (2002) there was a very significant 60% increase in 10 year survival for higher stage CRC patients who over expressed sialyl Lewis antigens X (sL(x)) and A (sL(a)). It’s important to recognize with these findings, that the percentage of patients who are diagnosed with CRC that are over expressing sL(x) and sL(a) is largely unknown, so the full-scale implications are not fully elucidated. However, it has been found in various studies that expression of sL(x) and sL(a) is most prevalent in Stage III and Stage IV colorectal cancers.
Repurposing OTC Drugs
Regardless of the key reasons for therapeutic success, it seems most of the studies involved have identified significant survival benefit and are suggestive of the need for a closer look from a clinical perspective. The {ReDo Group} has recently undertaken a new initiative called ReDO, for Repurposing Drugs in Oncology. Their focus is the identification of drugs, like Cimetidine and exploring therapeutic opportunities for a variety of cancers. The idea is a good one, as such a focus allows for greater opportunity and availability of cancer fighting drugs, while remaining very scientifically sound and exploring the implications of combining the highly available drugs like Cimetidine with other therapies.
Our Advice
Love Your Buns takes an active interest in exploring these sorts of secondary treatment options, particularly those that appear to help colorectal cancer patients that are diagnosed with a more advanced cancer (i.e., Stage III or Stage IV) at the start. Toxicity of Cimetidine over long periods of time appears to be very low and seems to be a safe addition to most patient’s treatment regimens. As always, we advise consultation with your oncologist, but please stay informed, do your research and be your own advocate!
Love Your Buns is a non-profit initiative aiming to remove stigma and improve awareness around rectal cancer, its prevalence and its symptoms. A growing epidemic in young adults, rectal cancer is easy to remove if caught early, however due to a variety of reasons, young adults are not likely to seek screening options like colonoscopies. This gap in screening is leading to more advanced disease at diagnosis and more challenging and strenuous treatment. We're working to Educate young adults to increase awareness of the signs and increasing prevalence of Rectal Cancer and to Empower informed decision making and Improve quality of life in Survivorship.
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