A practical guide for the complementary health care practitioner
In the training of chiropractors and other complementary and alternative health care practitioners, a general understanding of how physicians decide upon which chemotherapy drugs to use on a particular cancer patient is usually not covered in the academic curriculum. In the course of running a practice certain patients and/or their family members, whom you have known over the years, on occasion develop cancer. In these cases it is not uncommon for them to consult with you regarding nutrition, supplementation and other adjunctive measures that can be considered as part of complementary management of their condition. As such, it is valuable to have a working knowledge of how medical interventions act to help reduce the tumor burden. This article provides a basic overview of the various classes of chemotherapy agents that are commonly used today, along with the mechanism of action through which they kill cancer cells or interrupt their growth.
The Cell Cycle
As many chemotherapy drugs exert their effects at specific points in the life cycle of the cell, a quick review of the cell cycle is in order.
The normal cell cycle consists of the following sequential stages:
G0 Phase – resting diploid cells that are not dividing
G1 Phase – cells that have recently divided and are committed to continued proliferation
S Phase – follows G1 phase whereby cells undergo DNA synthesis
G2 Phase – premitotic rest interval (check point to see if DNA has properly reproduced itself)
M Phase – mitotic phase, chromosome condensation with cell division
Of interest is the fact that solid malignant tumors contain the following three types of cells:
Large tumors harbor more non-proliferating cells, which potentially make them more resistant to agents that selectively target dividing cells
Many oncologists use a combination of chemotherapy drugs concurrently in the treatment of most cancers. The thinking behind this method is as follows:
Classes of Chemotherapy Agents
A standard way to classify chemotherapy agents is put them into one of two categories:
The cell cycle or phase-specific drugs have their greatest killing effect when a cell is dividing whereby certain drugs target specific cell phases (e.g. M-phase).
Non cell cycle or non phase-specific drugs often remain in the cell and wait for cell division to occur, upon which they exert their anti-cancer effects, or bind to key enzymes inhibiting their function.
The following are some of the commonly used cell cycle dependent chemotherapy drugs and the specific stages of the cell cycle in which they exert their effects:
Anti-Metabolites – drugs that are structural analogues to naturally occurring metabolites involved in DNA and RNA synthesis. These drugs alter critical pathways to prevent cancer cells from synthesizing DNA or RNA. They exert their cytotoxic effects either by competing with normal metabolites for the catalytic or regulatory sites of a key enzyme or by substituting for a metabolite that is normally incorporated into DNA or RNA.
Examples Include: capecitabine, doxorubicin, floxuridine, gemcitabine, mercaptopurine, prednisone, thioguanine, cytarabine, fludarabine, hydroxyurea, methotrexate, procarbazine
Use of topoisomerase II inhibitors increase risk of developing a second cancer – acute myelogenous leukemia, which can be seen as early as 2-3 years after drug was given
M-Phase Or Mitotic Inhibitors
Mitotic Inhibitors are often plant alkaloids and other compounds derived from natural products. They inhibit mitosis or inhibit enzymes from making proteins needed for cell replication. They work primarily in the M-phase, but can damage cells in all phases. They are used to treat many different cancers including – breast, lung, myelomas, lymphomas, and leukemias. They often cause peripheral nerve damage (supplementation with alpha-lipoic acid may reduce this side effect or help repair the nerve damage as it has been shown to do in diabetic neuropathy)
Note: it is most interesting to see how many chemotherapy agents are actually derive from natural botanical sources
The following are some of the commonly used non-cell cycle dependent chemotherapy drugs:
Alkylating Agents – impair cell function by forming covalent bonds with amino, carboxyl, sulfhydryl and phosphate groups in biologically important molecules – most important sites are DNA, RNA and cellular Proteins.
These are also known as intercalating agents
Examples of Alkylating Agents:
Anthracyclines (tumor killing antibiotics) - these are antitumor antibiotics that interfere with enzymes involved in DNA replication. They work in all phases of the cell cycle and thus, are used widely in various cancers. They can permanently damage the heart if given in high doses. Lifetime dose limits are often placed on these drugs for this reason.
Concurrent supplementation with Coenzyme Q10 has been shown to protect the heart muscle in cases of Adriamycin use.
Examples of Anthracyclins:
Some of the newer chemotherapy drugs are classified as Targeted Agents. Here are some examples:
Examples Of Monoclonal Antibodies:
2. Small Molecules – these inhibit some key pathways that drive cancer cell division (particularly tyrosine kinase inhibitors):
3. Endocrine Therapy:
Tamoxifen and Raloxifen – selective estrogen receptor modulators (SERMs) that compete with estrogen for binding to estrogen receptors – slowing cellular proliferation
Aromatase Inhibitors – block aromatase enzyme (estrogen synthase) in fat cells, stromal cells, breast cancer cells, that converts androstenedione into estrone.
This article provides a general overview of the classes of chemotherapy agents that are commonly prescribed today by oncologists. Understanding the influence that these drugs have on killing cancer cells, or interrupting their mitotic potential, is a critical factor in deciding what dietary or supplementation practices would be synergistic to the action of the drug or would be in conflict. In addition to these chemotherapy agents there are also other oral drugs used (often off-label use) in the management of these cases, which should also be factored in to the nutrition and supplementation advice provided to a patient. A future article will address the off-label use of these drugs in cancer management.
One of the highlights of my professional career has been to teach a course on the Adjunctive Nutritional Management of Cancer to medical doctors and oncologists who are candidates in the Fellowship In Integrative Cancer Therapy Program taught through a division of the American Academy of Anti-Aging Medicine. These doctors have been most receptive and appreciative of the evidence-based protocols I have provided to them, and many use this information for the purpose of incorporating targeted nutritional and supplementation practices into the management of the cancer patients they see. In return, I have learned a great deal about medical cancer therapy from these practitioners, and other speakers at these conferences, including much of the information presented in this article.
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