Clinical research: Sodium bicarbonate

Professional info

A phase I/II study of oral bicarbonate as adjuvant for pain reduction in patients with tumor related pain

 

Sodium bicarbonate has been importantly promoted on the internet as a cancer therapy but without proper clinical evidence. Moreover a mechanism of action completely inaccurate was proposed, merely based on speculations, such as cancer is a fungus, which is not true.
Laboratory experiments showed that lowering the pH (increasing acidity) could prevent tumor dissemination (metastases).
Sodium bicarbonate has been investigated as an inhibitor of tumor acidity in laboratory experiments, but clinical studies are necessary to investigate whether this effect can be reproduced in humans.
Recent investigation also shows that cancer-related bone pain involves the reduction of peritumoral pH and activation of pain receptors.
This project aimed to explore the use of sodium bicarbonate in cancer patients, first as cancer-related pain therapy and afterwards as metastases inhibitor. Due to some practical and scientific constraints this project had to be closed prematurely. At the moment of closing this project it was found that:
• Sodium bicarbonate has no proper clinical investigation to support its recommendation as cancer therapy.
• There is pre-clinical data (sodium bicarbonate has been shown effective reducing tumors dissemination in mice) that makes it interesting for investigation but the feasibility of doing so is challenging.

 

Warning: A word about Simoncini: A Google search of “bicarbonate therapy and cancer” will invariably be led to Tullio Simoncini. He is an Italian physician who has been promoting bicarbonate therapy for a number of maladies, including cancer. He has promoted this aggressively on YOUTUBE and multiple websites. Simoncini is a medical doctor whose license to practice medicine was purportedly withdrawn in 2003, and in 2006 he was allegedly convicted by an Italian judge for wrongful death and swindling. Simoncini allegedly injected sodium bicarbonate to a breast cancer patient in the Netherlands, this patient died.
Tullio Simoncini claims that cancer is caused by a fungus and that it can be treated with sodium bicarbonate within days with no side effects. There is no scientific proof that cancer is caused by a fungus. Simoncini never produced any scientific proof to support his claims. Although Simoncini’s license is suspended he continues to administer his therapies in Italy and around the world.
Sodium bicarbonate is an interesting product whose mechanism of action in cancer remains to be elucidated, but from what is known today Simoncini’s theories are unlikely. His activities have importantly affected the development of serious scientific investigation on this product.

 

Location: Lee Moffitt Cancer Center, Florida (USA)
Collaboration: Amit Mahipal MD, Robert Gillies PhD

 

Why did we choose this project?

One of the most debilitating and demoralizing complications in cancer is pain. Cancer pain is frequently difficult to control even with high doses of narcotics. Both the cancer-induced pain and the effects of the narcotics are major factors in reducing the quality of life in cancer patients. In recent years it is becoming evident that tumor-related bone pain involves the reduction of peritumoral pH and activation of pain receptors. It is generally agreed that low pH surrounding metastatic lesions activates acid-sensing ion channels, ASICs.

There is pre-clinical data that shows that lowering the pH (increasing acidity) in cultures of cancer cells increases the incidence of metastases in mice that are injected with those cultures. Also, it was shown in pre-clinical investigation that lower pH increases factors that induce tumor invasiveness.
In addition, inhibition of tumor acidity has been shown to enhance susceptibility of tumors to weakly basic drugs.

The effect of bicarbonate is to increase the buffering capacity of the tumor, which inhibits acidosis. Bicarbonate can neutralize tumor-derived acid without affecting systemic pH.

This trial was supported as an initial step to explore in further studies the effects of pH manipulation on metastasis in humans.
 

The aim of the project?

The aim of this project was to determine the maximum tolerated dose (MTD) of oral sodium bicarbonate capsules for patients with tumor-related moderate to severe pain. As well as to evaluate the proportion of patients with greater than 30% improvement in pain intensity by visual assessment scale at 4 weeks compared to baseline without a corresponding increase in opioid regimen. It was intended, once the MTD was determined, that other projects testing sodium bicarbonate with anticancer drugs in development would have been evaluated in order to investigate the metastases development inhibition.

 

How did we approach this problem?

A collaboration to start a clinical trial was stablished. This trial was a single institution study, non-randomized, single arm Phase I/II study to evaluate the safety and efficacy of adjuvant therapy with sodium bicarbonate for tumor-related pain. A standard 3+3 Phase I study with three dose escalations would be used to determine the MTD of sodium bicarbonate in patients with tumor related pain. Once the MTD was determined, the cohort would have been expanded and 25 patients would have been enrolled and evaluated for bicarbonate therapy efficacy.

Patients started taking 10 capsules a day, each capsule of 930 mg, they split the intake of the medication through the day in a schedule set by the researchers. Through the study, according to the tolerability of side effects, the doses would have been increased. Patients who were less than 70% compliant with their medication schedule would have been removed from the study drug. Patients would have continued sodium bicarbonate therapy for 4 weeks. Following the conclusion of the study, patients could choose to continue sodium bicarbonate therapy provided they are monitored by their treating physician on a monthly basis.

Patients with a good tolerance to study therapy and with at least a 30% improvement in pain intensity compared to baseline after 28 days of therapy and who wish to continue study therapy would have been allowed to continue sodium bicarbonate therapy under the direction of their treating physician. Patients without at least a 30% improvement in pain intensity at 28 days would have to discontinue study therapy.

 

What did we find?

This project started in July 2013. It was closed down during phase I due to slow patient recruitment at the researchers’ request in February 10th 2015.
Phase I was going to recruit patients in 4 cohorts, but at closing only 2 cohorts were recruited.

In total 9 patients took part in the study, however only 4 patients completed the study, from these 3 patients in cohort 1 and 1 patient in cohort 2. Patients could hardly comply to the treatment protocol.

Cohort 1 received 9.3 grams/day of sodium bicarbonate (or 10 capsules of 930 mg), for cohort 2 the dose was increased to 18.6 grams/day (or 20 capsules of 930 mg), divided in 3 takes. This was the dosage of sodium bicarbonate being analyzed at the moment this project stopped. However, due to the premature closure of this project MTD was not found.

 

Based on the project results, our message to patients:

Sodium bicarbonate remains an interesting product to be investigated. The pre-clinical research performed so far is encouraging, however without proper clinical investigation it cannot be recommended as cancer therapy. Investigating this product is methodologically challenging, patients’ recruitment is difficult because there are other products being investigated in cancer whose level of evidence is high and from which patients could potentially benefit as well. In addition the estimated doses for efficacy and the administration schedule planned based on pre-clinical investigation makes compliance difficult.