Low-Dose Chemotherapy
Chemotherapy was developed as a result of observational studies of mustard gas used during World War II. Following the discovery of nitrogen mustard, Dr. Sidney Farber of Harvard noticed that a compound called aminopterin caused remission in acute leukemia in children. In the following years, much of the research into how to treat cancer would center around finding new chemotherapeutic agents. Aminopterin was a predecessor of methotrexate, a popular cancer drug still used today.
How Does Chemotherapy Work?
Chemotherapy kills rapidly growing cells (i.e., cancer cells). Despite its documented effectiveness, chemotherapy is one of the most feared treatments in modern medicine. This fear is not without reason, as the side effects of chemotherapy are often as unpleasant as the cancer it is being used to fight. However, chemotherapy does not have to be a dirty word. Chemotherapy has mountains of evidence supporting its use, and unbeknownst to many people, a significant number of chemotherapy agents are made from naturally-occurring, plant-based substances. I regularly use chemotherapy in my practice, but the way we use it differs dramatically from conventional oncology.
How Are Chemotherapy Doses Chosen?
Chemotherapy agents are dosed based on a patient’s height and weight. The result is what is known as maximum tolerated dose, or MTD, chemotherapy. We often refer to this as full dose chemotherapy. This method came into prominence after childhood acute lymphoblastic leukemia (ALL) was successfully treated this way. Since that time, it has been shown to be a consistently effective approach in a few other cancers, such as testicular cancer and Hodgkin lymphoma. However, these cancers are less complex and have significantly fewer mutations than most other cancers. Cancers such as breast, prostate, and colorectal do not respond nearly as consistently to full dose chemotherapy, and side effects can be significant.
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Do We Really Need to Use Such High Doses?
It is tempting to want to be as aggressive as possible when it comes to treating cancer. We can see this in the verbiage used today when it comes to cancer, such as “the war on cancer,” “fighting cancer,” “killing cancer,” etc. In one respect, this desire to eliminate cancer as quickly and intensely as possible is understandable, since cancer is a scary and aggressive disease. However, scientists have been questioning the “more is better” approach to chemotherapy for quite some time. With full dose chemotherapy, there is a large window of time between the administration of the initial treatment and the subsequent treatment. Typically, patients will receive treatment once every 1-3 weeks, depending on the chemotherapeutic agent(s) used, the type of cancer, and the stage of cancer. With this method, side effects frequently occur, including immune system suppression, nausea, vomiting, diarrhea, and fatigue. Administering full-dose chemotherapy more often than this would likely cause even more terrible side effects.
During that window of time between chemotherapy treatments, however, you give cancer cells that survived the treatment the opportunity to build resistance to the drug. We have learned that most tumors contain a proportion of cancer cells that are sensitive to treatments such as chemotherapy, while the remaining cancer cells are resistant to it. Maximum tolerated dose chemotherapy kills the sensitive cancer cells, leaving behind a population of resistant cells which are essentially unaffected by the chemotherapy. These resistant cells are then able to use nutrients and other factors to aggressively grow and thrive. This is why we often see a dramatic reduction in tumor size and cancer markers during the first cycle or two of MTD chemotherapy, but aggressive recurrence of the cancer in the months that follow. Unfortunately, the success seen in those early cycles is nearly impossible to maintain, as subsequent chemotherapy treatments against the remaining resistant cells provide little to no results.
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The Value of Lower Dosing
Nearly 20 years ago, several forward-thinking scientists began testing lower doses of chemotherapy, given more frequently than full dose regimens. This lower dosing, which typically uses between 10-30% of the full dose, is known as fractionated chemotherapy, and when we give these lower doses more frequently, we refer to it as metronomic chemotherapy. There are several distinct advantages to this approach of giving smaller doses more often. A strategy which administers lower doses of chemotherapy more frequently has been developed. This is known as metronomic chemotherapy. Because the dosage used each time with metronomic chemotherapy is less––or fractionated––the side effects are greatly mitigated if not non-existent, and the collateral damage to healthy cells is also greatly reduced. Another advantage of lower doses of chemotherapy given in this fashion is an anti-angiogenic effect, meaning that blood supply to the cancer is decreased. Not surprisingly, such an approach has also been found to greatly reduce toxicity. Finally, metronomic chemotherapy has been shown to stimulate the immune system, rather than lowering its function.
Using Insulin to Optimize Treatment
In an attempt to maximize the efficacy of fractionated chemotherapy, we take advantage of the fact that cancer cells have many more receptors for insulin and glucose on their cell membranes. This is the basis for insulin potentiation therapy––IPT. By giving insulin just prior to chemotherapy, we believe that cancer cells become desperate for glucose and anything else we give with it. It is at this point where we administer intravenous glucose, known as dextrose, along with multiple chemotherapeutic agents strategically and carefully chosen for that patient based on advanced testing. We believe this allows us to better target the chemotherapy drugs directly toward cancerous cells.
