What is insulin-supported chemotherapy? Does it have a role in cancer treatment?

What is insulin-supported chemotherapy?

Insulin-supported chemotherapy is based on combining insulin with chemotherapy drugs to allow more drug to enter cancer cells. It is also called KemoTermi. It is claimed to produce a greater effect with less chemotherapy and fewer side effects. It involves no discovery of a new drug but aims to increase the effectiveness of existing chemotherapy medicines.

What is its history, and for which conditions is it used?

Insulin-supported treatment was first proposed in 1932 by Mexican physician Donato Perez Garcia. Initially developed mainly for syphilis, it was later also tried for arthritis (joint inflammation), colitis (colon inflammation) and asthma. In 1939, Mexico’s Ministry of Health stated that insulin-supported treatment for syphilis merited investigation; however, newly discovered antibiotics treating syphilis very effectively at the same time pushed insulin treatment out of favor. Seeking new avenues, Dr. Perez then claimed in 1947 that insulin treatment was effective in cancer. Clinical research proving these claims, however, has never been published in peer-reviewed journals. A few small studies later published by other research teams also failed to confirm them.

What is the mechanism of action?

Insulin-like growth factor (IGF-1) is known to play a role in cell proliferation, migration and adhesion. In some cancers, cellular IGF-1 receptors have been shown to be overactive. On this basis, cancer cells are claimed to be more sensitive to insulin and insulin-like growth factor (IGF-1).

Insulin is the hormone that allows blood sugar (glucose) to enter cells. Externally administered insulin therefore increases movement of sugar from blood into cells. It is consequently claimed that administering insulin stimulates IGF-1 receptors in cancer cells and increases cell membrane permeability. Cancer cells are also said to need more sugar, further increasing membrane permeability. Increased permeability is believed to allow more drug into cancer cells. It is thus claimed that one quarter to one tenth of usual chemotherapy doses can provide the same effect with fewer side effects. None of these claims, however, has so far been proven or established on scientific grounds.

Another hypothesis holds that insulin affects the S phase of the cell cycle, making the tumor more vulnerable to drugs acting specifically in this phase.

What are the results of studies on insulin-supported chemotherapy?

The literature contains only a few small studies and case reports on insulin-supported treatment in cancer patients.

A clinical study evaluating 16 patients with advanced prostate cancer divided them into 2 groups receiving different chemotherapy drugs with insulin. After cycle 6, PSA levels indicating disease course showed arrested progression in 4 patients, partial response in 8 and progression in 4. However, since both groups received insulin, the insulin-specific effect cannot be assessed. Long-term outcomes are also unknown.

Another study involving 30 women with multidrug-resistant advanced breast cancer divided them into 3 groups receiving methotrexate chemotherapy alone, methotrexate with insulin, or insulin alone. Assessment after 8 weeks found less disease progression and tumor growth in the methotrexate-plus-insulin group. However, the study’s scope and methodology are insufficient for a firm conclusion. Indeed, basic parameters such as quality of life and survival were not assessed, and long-term outcomes were not reported.

There are also a few case reports of insulin-supported chemotherapy in the literature. Although some positive results were obtained, it is unknown whether the effect was due solely to chemotherapy or whether insulin contributed.

In a laboratory study in China, insulin increased the effect of etoposide chemotherapy in human esophageal and lung cancer cells. Another Chinese laboratory study reported that insulin increased paclitaxel’s cancer-cell-killing effect in human endometrial cancer cells. Another laboratory study of human tumor cells found only a small difference in chemotherapy sensitivity in cells receiving insulin. A substance or method being effective in the laboratory merely indicates that it may be tested clinically; it does not mean that it will have the same effect in the human body without harming other cells. On the contrary, of perhaps thousands of substances killing cancer cells in the laboratory, only a few produce the same effect in the human body.

Memorial Sloan Kettering Cancer Center, a leading cancer institution, also states that this method has no established beneficial effect in cancer treatment and may instead be dangerous by causing excessive blood sugar reduction.

Is insulin-supported chemotherapy entirely harmless?

One fundamental argument used by advocates is that the method is entirely harmless and uses licensed drugs that have existed for many years. That insulin and chemotherapy drugs are licensed and approved does not mean there are no concerns about their use this way. Insulin has no indication for increasing cancer drug effectiveness. Such use is at physicians’ discretion and is not prohibited under certain conditions. Of course, that does not mean it is without risk.

Low blood sugar (hypoglycemia) is a leading side effect. Giving insulin to someone without diabetes can lower blood sugar and cause headache, palpitations and loss of consciousness. Similarly, in people with diabetes taking blood-sugar-lowering medicines, it may reduce blood sugar below desired levels.

Although patients usually receive only one quarter to one tenth of standard chemotherapy doses in this method, insulin is claimed to ensure the same effect.

Clinical studies have not demonstrated such an insulin effect to date. This method may therefore lead to inadequate treatment, failure to recover or even disease progression. Moreover, using chemotherapy at such low doses may increase drug resistance.

It is claimed that insulin increases cancer-cell permeability to chemotherapy drugs, allowing the same effect at lower doses with fewer side effects. However, there is no evidence that insulin increases permeability in cancer cells but not normal cells. Insulin could therefore also increase chemotherapy permeability in normal cells and worsen side effects.

Beyond all this, insulin may also increase tumor growth. Many cancer cells contain large numbers of insulin and insulin-like growth factor (IGF-1) receptors. Insulin and IGF-1 may directly stimulate cell division, growth and spread in these cells. A comprehensive study published in 2004 in the leading medical journal Lancet evaluated the relationship between cancer risk and blood levels of insulin-like growth factor (IGF-1) and its main binding protein IGFBP-3. It reported that high IGF-1 levels increased prostate and breast cancer risk, and high IGFBP-3 levels increased breast cancer risk.

So what should be done?

In conclusion, insulin-supported chemotherapy has no evidence of any beneficial effect in cancer, lacks a scientific foundation and instead carries serious risks. No leading oncology institution currently supports it. Resorting to a method based entirely on assumptions, about which nothing is known, is no different from gambling with one’s life. Some suggest that this inadequately studied and unsupported method could at least be used for terminal cancer patients. However, it involves no new drug discovery; essentially, it aims to reduce side effects by giving existing chemotherapy drugs at lower doses. In conclusion, at present, insulin-supported chemotherapy is not appropriate for any cancer type, at any stage or under any circumstances.