CATEGORIES OF CANCER DRUGS

There are literally hundreds of different chemotherapy agents currently in use, and each one is grouped into a category or class. The reason we have so many is because no two types of cancer are alike and therefore the treatments won't be the same; for example, what works to destroy breast cancer will not work as well to destroy brain cancer. To compound this problem most cancers have different versions of themselves. For example, breast cancer can be estrogen fueled, or progesterone fueled, or HER2 positive, or be "triple negative" (meaning it is none of the first three), or be inflammatory (meaning it spreads through the breast without creating a solid tumor) or it can be any combination of these. Although these are all breast cancers, each of them require a particular combination of chemotherapy agents/radiation therapy in order to destroy them. Because different types of cancers require different methods to be destroyed, this requires the medical world to have many different agents available to save lives.

When you are facing chemotherapy treatment it is important for you to have some idea of which chemotherapy agents you are prescribed and what this means for your health. This information is an important foundation for receiving the best holistic care to match your treatments. Therefore, this page is provided so you can have a basic knowledge of your chemotherapy class and what it can mean for your holistic treatment plan.

I strongly encourage you to speak with your oncologist if you have any questions or concerns, or if you need further information regaring your chemotherapy agents.

ALKYLATING AGENTS

Alkylating agents are the most commonly used chemotherapy drugs; although they can be used for many kinds of cancers they tend to work better on slower growing tumors. Alkylating agents work by binding directly to the cancer cells' DNA strands in several places resulting in mutations which cause them to be unable to multiply (either by self-destruction or inability to reproduce). When enough cancer cells are deactivated with these agents the tumor is destroyed. Although this damage to DNA is necessary to destroy the cancer, it does carry the risk of long-term damage to bone marrow. In rare cases this may lead to the development of acute myelogenous leukemia (AML) within ten years after treatment is finished.1 Fortunately, this risk is “dose-dependent,” which means lower doses of these agents result in a lower risk. I strongly encourage you to speak with your oncologist if you have concerns about this risk.

Alkylating agents are divided into sub-classes: Alkyl sulfonates, ethylenimines, hydrazines, nitrogen mustards, nitrosureas, and triazines. The one particular type of alkylating agent known as “nitrosureas” has the unique ability to cross the blood-brain barrier. The blood-brain barrier is a filtering system built into the brain and spinal cord to keep many harmful molecules out of the central nervous system. The nitrosureas molecules are one of the few chemotherapy agents able to filter through this system, making them an effective treatment for patients diagnosed with brain tumors.

The biggest hurdle with alkylating agents is that sometimes the cancer cells can develop a resistance to it, rendering the drug less effective. This can happen because sometimes the cancer cells make use of a certain enzyme, “MGMT”,2 that is designed to repair DNA damage. Drugs which inhibit the activation of this enzyme may be added to your treatment regimen in order to maintain the agent's effectiveness. Although there are some prescription drugs to help reverse this resistance, there are also holistic methods which can also help reverse this resistance as well.

Alkylating agents include (generic names): bendamustine, busulfan, carmustine, chlorambucil, dacarbazine, cyclophosphamide, estramustine, ifosfamide, lomustine, mechlorethamine, melphalan, prednimustine, streptozocin, temozolomide, thiotepa, trabectedin, trofosfamide, and uramustine.

ANTIMETABOLITES

Because antimetabolite agents are so similar to your body's own natural substances an agent can interfere with cancer cell growth by substituting itself for some of the genetic material being built during cancer cell reproduction. This can result in either cancer cell death or simply render the cancer cell unable to multiply, depending upon the agent used and the type of cancer being targeted. Subclasses of antimetabolites include folate analogues, pyrimidine analogues, and purine analogues.

Folate analogues, a.k.a. folate antagonists, are substances which decrease the production of folic acid, also known as vitamin B9. Folic acid is essential for the formation of nucleotides which are basic building blocks of DNA. It was observed that leukemia patients whose diets were low in folate/folic acid also had lower white blood cell counts than leukemia patients who had normal levels of folate in their diets. This observation eventually led to the development of the folate antagonist methotrexate, which is one of the most commonly used folate antagonists today as it is effective against several types of cancers. One big drawback to methotrexate treatment is that drug resistance is a common issue. Although there are some prescription drugs to help reverse this resistance, there are also holistic methods which can also help reverse this resistance as well.

Pyrimidine analogues, a.k.a. pyrimidine antagonists, tend to be associated with liver and gall bladder injury, therefore you should be sure your oncologist knows if you have any past or present problems with your liver or gall bladder. In most cases these risks are related to dosage and method of delivery, depending upon the particular agent being used.

Purine analogues, a.k.a. purine antagonists, tend to be associated with an increased risk in developing infections. There is only a handful of purine analogues that are relevant for cancer treatment. Ex-vivo studies have shown that the use of the dietary supplement resveratrol along with purine analogues when treating for chronic lymphocytic leukemia (CLL) helped increase cancer cell self-destruction without harming surrounding healthy cells. According to one study “[resveratrol] may be used as a single agent, especially in older persons for whom there are some limitations for the use of aggressive treatment...a lower purine analogue dose could potentially be used in combination with resveratrol because of their combined effect.”3 (Resveratrol is a natural substance found in red wine, red grapes, and commercial supplements).

Antimetabolite agents include (generic names): capecitabine, cladribine, clofarabine, cytarabine liposomal, decitabine, floxuradine, fludarabine, fluorouracil, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, nelarabine, pemetrexed, pralatrexate, and thioguanine.


ANTI-TUMOR ANTIBIOTICS

Anti-tumor antibiotics, a.k.a. Anti-neoplastic antibiotics, are produced from a bacteria species known as Streptomyces which was found to have anti-tumor properties in the 1960's.4 These types of antibiotics are not like the antibiotics that are made for treating infections. Instead, these antibiotics work against cancer cells by changing the DNA inside them which keeps them from multiplying. This class of chemotherapy agents is divided into three sub-classes: Anthracyclines, Chromomycins, and Miscellaneous.

Although anthracyclines increase survival rates it also is a known risk in causing heart damage, especially in the left ventricle of the heart.5 Due to this risk there are oftentimes lifetime dose limits put in place to protect the organ. This means that individual patients are not allowed to continue having treatment with anthracyclines once they've reach a certain level of exposure to them in their lifetimes. A study published in 2014 showed that consuming too much iron during anthracycline treatment tended to increase the risk of heart damage in patients using them,6 therefore your iron levels should be monitored during treatment. Do not take iron supplements or eat a diet high in iron without discussing this with your oncologist first.7 Because of this risk of heart damage patients using this class of agents are carefully monitored to ensure heart health because this damage is not reversible. Anthracyclines are also what's known as a topoisomerase II inhibitor, which carries a low risk of developing mixed lineage leukemia (MLL) after treatment is complete. Fortunately, leukemia caused from topoisomerase II inhibitors is easier to treat than leukemias caused by alkylating agents. Anthracycline agents include (generic names): Daunorubicin, doxorubicin, epirubicin,8 idarubicin, mitoxantrone,9 and valrubicin.

Chromomycins include (generic names): Actinomycin-D (a.k.a. dactinomycin)10 oligomycin, olivomycin, mithramycin, and plicamycin. At the turn of the millennium plicamycin and mithramycin were withdrawn from the market due to their extremely toxic properties.

Miscellaneous agents include (generic names): bleomycin and mitomycin. Bleomycin's most notorious side effect is scarring of the lungs (a.k.a. pulmonary fibrosis), so if you already have health issues with your lungs you must be sure your oncologist is aware before you take bleomycin. This scarring is more likely to occur in elderly patients and those who have been given a higher total dose of the agent. In contrast, mitomycin's effects on the lungs is much rarer.

In general, anti-tumor antibiotics are known for also causing bone marrow suppression, liver problems, and kidney problems. Be sure you speak with your oncologist about the risks involved and what it means for your particular health situation before using these agents.

CORTICOSTEROIDS

Corticosteroids are steroid based substances naturally made in your adrenal glands (which sit atop each kidney). When a patient is given prescription corticosteroids the adrenal glands tend to reduce their production of the substance, therefore, when you no longer need the prescription you will need to slowly wean yourself off the drugs to give your adrenal glands a chance to begin increasing production. The most common forms of corticosteroids prescribed are prednisone, prednisolone, methylprednisolone, dexamethasone, and hydrocortisone. Because corticosteroids affect the adrenal glands most patients are not ordered to have long-term corticosteroid treatment. Never suddenly stop taking your corticosteroids without your physician's oversight because you risk experiencing withdrawal symptoms such as weakness, body aches, joint pain, and severe fatigue. The length of your corticosteroid treatment depends upon the type of cancer you have and which other treatments you are being prescribed.

Corticosteroids have many uses when it comes to treating cancer including: Using it as supportive treatment with chemotherapy, reduction of inflammation, reducing the immune response after a bone marrow transplant, helping to increase appetite, and to help relieve some of the side effects caused by certain chemotherapy regimens. Corticosteroids can be given as an oral medication, an intramuscular injection, or as an injection into your vein.

Side effects of corticosteroid treatment may include: Digestive problems, insomnia, yeast infection, anxiety, weight gain, cataracts, osteoporosis, thinning of the skin, increased risk of infection, and slower wound healing. Other side effects may occur; speak to your prescribing physician.

Because corticosteroids will suppress your immune system, patients using them must avoid receiving live vaccinations and avoid people who have an active infection with chicken pox, shingles, or whooping cough (a.k.a. pertussis).

DIFFERENTIATING AGENTS

Differentiating therapy is founded on the idea that certain types of cancer cells were normal cells which were stunted or have reverted to an immature state resulting in a lack of their ability to control their growth. Differentiation therapy is used for "rebooting" the cancer cell to re-start the process of maturation in order to return to a normal state and regain control of their growth. Instead of destroying the cells, this form of therapy reigns in their growth and allows conventional chemotherapy agents to destroy the cancerous cells. Because differentiating agents aren't actually killing cells they tend to be less toxic and cause less side effects than other chemotherapy agents.

Differentiating agents tend to be retinoid-based substances which are similar to vitamin A. The first differentiating agent to be discovered was Tretinoin,11 a topical acne treatment, which has been shown to also induce complete remission in roughly 70% of acute promyelocytic leukemia (APL) cases when used as an oral agent. Patients should not take this to mean they should orally consume their prescription acne treatments for their leukemia, as acne treatments are not formulated for oral consumption. Leukemia patients using this agent are usually patients who do not respond to, or cannot use, anthracycline agents. It is not used as maintenance therapy in such patients.

When used for leukemia there may be side effects such as blood clots, liver damage, bleeding disorders, pneumonia, digestive issues, weight changes, heart problems, blood pressure issues, and pain. Although differentiating agents are commonly used for different types of leukemia researchers are also looking into the potential for using them against solid tumors as well.

Differentiating agents include: alitretinoin, bexarotene, and tretinoin.

EPOTHILONES

Epothilones are anti-tumor substances derived from a bacteria known as Sorangium cellulosum. There are several known epothilones, identified as Epothilones A -F, which have been tested in laboratories and in human cancer patients. The mechanism of action in epothilones is similar to that of taxanes even though their molecular structure isn't as complex as the taxanes (see the subheading “Plant Alkaloids”). Epothilones have been observed to have better effect than taxanes and they are also more readily dissolved in water. In contrast, taxanes need solvents to allow the taxanes to mix with water; solvents which may cause toxic effects on a patient's heart. Since epothilones do not need these solvents they are a safer alternative to taxanes. It has also been observed that Epothilone-B does not induce the inflammatory response common to taxanes such as paclitaxel. In most cases epothilones are combined with other chemotherapy agents to better target the specific cancer being treated. Usually the combination is administered as an intravenous treatment.

Although epothilones have benefits over taxanes, these are not without known side effects. The most common side effects tend to be weakness and pain in the joints. Less common side effects include mouth sores and headaches.

IMMUNOTHERAPY

Cancer immunotherapy, also known as biologic therapy, is a system of treatment in which a patient's immune system is used to help fight the cancer. This can be accomplished in two ways: (1) Stimulating the patient's own immune system to work harder against the cancer, or (2) Giving immune system components to the patient from an outside source. Immunotherapy works better on some types of cancer than it does on others and comes in various forms such as: targeted therapy (monoclonal antibodies), cancer vaccines, immune modulators, oncolytic virus immunotherapy, cytokines, and more.

Although immunotherapy can be a very effective treatment, there are certain barriers that sometimes happen. For example, your cancer cells may not be different enough from your normal cells resulting in your immune system being unable to recognize them as dangerous. In other cases, some cancer cells may release substances which suppress the activity in your immune system. In yet other cases your immune system may simply be not strong enough to destroy the cancer.

Although this type of therapy uses biological substances it can still cause certain side effects. The side effects most commonly associated with immunotherapy include: Pain, fatiuge, fever, chills, dizziness, blood pressure changes, nausea, and soreness, among others. Discuss with your oncologist which specific side effects you need to be aware of, as different therapies may produce different side effects.

Immunotherapeutic agents can be administered intravenously, orally, topically, and intravesically (into your urinary bladder). Immunotherapy agents include: Cancer vaccines, interleukins, interferons, and monoclonal antibodies.

PLANT ALKALOIDS

Plant alkaloids are cell-cycle specific agents created from certain types of plants. Subclasses of plant alkaloids include vinca alkaloids, taxanes, epipodophyllotoxins, and camptothecan analogs.

Vinca alkaloids and taxanes are both subclassed as microtubule inhibitors, a.k.a. anti-microtubule agents, a.k.a. mitotic inhibitors.12 The vinca alkaloids are made from the periwinkle plant (catharanthus rosea) and are given as an intravenous treatment. A well-known side effect of vinca alkaloids is their risk of causing nerve damage, also known as neuropathy. There are holistic therapies which can reduce this risk. Vinca alkaloids include: vinblastine, vincristine, vindesine, and vinorelbine. The taxanes are made from the bark of the Pacific Yew tree (Taxus brevifolia). A well-known side effect of taxanes is their risk of lowering blood counts in patients. There are holistic therapies which can reduce this risk. Taxanes include agents such as: cabazitaxel, docetaxel, and paclitaxel. Docetaxel (brand name:Taxotere) is associated with permanent hair loss as a side effect (unlike most other chemo agents in which the hair re-grows after treatment).

Camptothecans and epipodophyllotoxins are known as topoisomerase inhibitors. Topoisomerase inhibitors are subclassed into type I and type II, according to which enzyme they influence.13 Camptothecan analogs are derived from the Asian Camptotheca acuminata tree and are topoisomerase type I inhibitors. Epipodophyllotoxins are derived from the May apple tree and are classified at topoisomerase type II inhibitors. Type II inhibitors carry the risk of developing acute myelogenous leukemia (AML) as soon as 2 years after the treatment is finished. Although anthracyclines are also topoisomerase inhibitors, these particular agents carry a lower risk. Fortunately, leukemias caused from topoisomerase II inhibitors are easier to treat than leukemias caused by alkylating agents.

PLATINUMS

Platinum agents are easily identified because their names contain the suffix “ -platin” such as carboplatin, cisplatin and oxaliplatin. Although platinums are not alkylating agents they are oftentimes placed in that category because they perform similarly to alkylating agents.

Although platinums are less likely to cause leukemia than alkylating agents, these still carry some risk, primarily with cisplatin and carboplatin. The risk of leukemia is dose dependent: The higher the dose of the agent the higher the risk of leukemia. The risk of developing leukemia is increased even more so if radiation is given along with the chemotherapy agent.

A Chinese study investigated the effects of combining platinum therapy with xiaoji decoction, a TCM14 formula. This randomized, single-blind study followed 40 patients with non-small cell lung cancer. 15 Twenty of the patients were given conventional treatment and twenty were treated with a combination of platinum agents, infusions of cytokine-induced killer cells, and the xiaoji decoction.16 Those who were given the infusions and decoction during treatment experienced increased survival rates and longer periods of progression-free survival.17

Platinum-based alkylating agents may cause magnesium deficiencies in patients, therefore it is essential that you take any magnesium supplements that may be prescribed by your oncologist. Take note that too much magnesium can cause severe diarrhea and stomach cramping, heart rhythm issues, low blood pressure, confusion, and death, therefore take only the amount prescribed for you. Also, be aware that magnesium can interact with antibiotics, diuretics, blood thinners, muscle relaxers, and blood pressure medications. Let your prescribing physicians know if you have any kidney problems before starting magnesium supplementation.

TARGETED THERAPY DRUGS

Targeted therapy is a system of treatment in which specific genes or proteins in the cancer cells are targeted for interference in order to prevent the cancer cells from multiplying. This is in contrast to chemotherapy agents which indiscriminately kill rapidly dividing cells such as healthy hair follicles, mouth membranes, and cells composing the digestive tract. This destruction of the healthy cells is oftentimes the cause of hair loss, mouth sores, and nausea associated with certain chemotherapy treatments. Targeted therapy may go by other names such as “molecular targeted therapies” or “precision medicine.” In most cases targeted therapy is used in tandem with chemotherapy in order for the patient to get the most benefit. There are two main types of targeted therapy: Monoclonal antibodies and small-molecule agents.

Monoclonal antibodies block receptor sites on and around cell surfaces, preventing cancer cell growth. These antibodies are too large to penetrate the surface of a cancer cell however they oftentimes help funnel chemotherapy agents into the cancer cells, in effect helping your chemotherapy agents work better. Monoclonal antibody agents are usually identified by the suffix “-mab”, (such as brentuximab vedotin, labetuzumab, trastuzumab, and vandortuzumab vedotin, etc.). These agents are usually given through intravenous methods. Monoclonal antibodies only target specific proteins unique to the cancer cells and therefore do not tend to affect healthy body cells.

Small-molecule agents are oral agents which block the process needed for cancer cells to multiply. Oftentimes this means blocking the process of angiogenesis. These are small enough to enter into the cancer cells to do their work. Most of these agents are identified with the suffix “-nib” (such as crizotinib, lapatinib, trametinib, etc.), though there are a few exceptions.18 Many small-molecule agents are subclassed as tyrosine kinase inhibitors, serine and threonine kinase inhibitors, and small molecule drug conjugates.

According to the National Cancer Institute, subclasses of targeted therapy include:

Different cancer tumors will have different targets, therefore what works for one cancer will not always work for another. For example, an oncologist may be treating one woman with HER2 positive breast cancer and another woman with ER postive breast cancer ("Positive" means these cancers contain proteins which accept particular biological substances that help fuel the cancer). Although both are breast cancers they are each different kinds of cancer with different kinds of receptors; therefore each would require a different plan of targeted therapy. Due to these differences among tumors it is important that your oncologist orders tests to gather information about your cancer's genetics, proteins and other features in order to prescribe the most effective targeted treatment for you.

Although using targeted therapy may seem like it should be a simple matter once the information is gathered, be aware that this is not always the case. Having a specific target for the agent does not guarantee that the tumor will respond to the agent. This can happen for many reasons: Sometimes the tumor becomes resistant to the therapy – this usually occurs through genetic mutations happening within the cancer cells. Sometimes a target turns out to be not as important as the doctor originally thought. Other times the side effects from the therapy may be too much for the patient to continue treatment with.

Side effects that may occur when using targeted therapy may include: Skin issues, nail problems, issues with blood clotting, slow wound healing, high blood pressure, and eye problems. Depending upon the targeting agent used there may be other side effects also. Be sure to discuss these with your oncologist. It is interesting to note that certain side effects of certain targeted therapies are sometimes associated with a better outcome for the patient. For example, it has been observed that patients treated with erlotinib or gefitinib who develop an acne-like rash tend to fare better than patients taking the same agents who do not develop the rash. Or, patients being treated with bevacizumab who develop high blood pressure fare better than patients who do not have blood pressure changes while using the agent. Of course, this should not be taken to mean a lack of certain side effects indicates a poor outcome; each individual case is different from the next.

 

COMBINING HOLISTIC THERAPY WITH CANCER DRUG TREATMENTS

Each class of agents has its own roster of side effects and risks. This is because cancer, being a very aggressive disease, takes aggressive treatment to destroy it; this results in the uncomfortable effects of the treatment. Do not be discouraged by this. Not only are there prescription medications that can reduce some of these problems, most of these problems can be also be reduced with evidence-based holistic therapies. Depending upon your situation, the proper combination of prescription treatments and holistic methods helps a great deal in helping your body destroy the cancer, alleviating side effects, and reducing drug-related health risks.

It is important to know, however, that when you choose to use holistic therapies alongside your chemotherapy treatments you must discuss this with your oncologist before starting. This is because, depending upon your situation, some holistic therapies may require some adjustments in your chemotherapy dosage, schedule, or even a change in your chemotherapy agent altogether. Because no two individuals have identical health situations the variables are endless, therefore you must keep both your oncologist AND your holistic practitioner informed about each other's recommendations in order to receive the best treatment for YOU.

 

1 Agents associated with this risk include: busulfan, carmustine, chlorambucil, cyclophosphamide, lomustine, mechlorethamine, and melphalan. AML can be difficult to treat.
2 Also known as Omega 6-MethylguanineDNAmethyltransferase, and is sometimes written as O6-MethylguanineDNAmethyltransferase
3 Annals of Hematology, February 2011, Vol.90, No.2, pp. 173-183 “Resveratrol Increases Rate of Apoptosis Caused by Purine Analogues in Malignant Lymphocytes of Chronic Lymphocytic Leukemia” Monika Podhorecka, et al
4 Streptomyces is a spore-producing bacteria which resembles a fungus, therefore some sources erroneously identify this microorganism as a fungus.
5 The heart has four chambers for blood flow: Two upper chambers called the atria, and two lower chambers called the ventricles.
6 Frontiers in Pharmacology, Feb. 26, 2014, Vol.5, No.25, “The role of iron in anthracycline cardiotoxicity” Elena Gammella, et al
7 Foods high in iron include: Red meat, pork, poultry, seafood, beans, dark greens leafy vegetables, dried fruits, and fortified cereals. Iron from animal-based foods is more easily absorbed in your body than iron from plant foods. Vitamin C products and supplements also increase absorption of iron.
8 Epirubicin is less damaging to the heart than doxorubicin, though a risk does remain.
9 Mitoxantrone an agent derived from anthracenedione, which is a derivative of anthraquiones in the streptomyces bacteria.
10 Actinomycin-D is also known as a polypeptide antibiotic.
11 Also known as all-trans-retinoic acid (ATRA).
12 “Mitotic inhibitor” means it inhibits the process of mitosis, i.e. cell replication.
13 Mitoxantrone, an anti-tumor antibiotic, is also subclassed as a toposiomerase II inhibitor.
14 TCM = Traditional Chinese Medicine.
15 Journal of Drug Metabolism and Toxicology, Sept. 7, 2015, “Effect of Chinese Medicine Xiaoji Decoction Combined with Platinum-based Chemotherapy and Transfusion of Cytokine-induced Killer Cells in Patients with Stage III B/IV Non-small Cell Lung Cancer” Li Liuning, et al
16 Xiaoji decoction ingredients include: Milk vetch (Astragalus mongholicus), Coriolus versicolor, (a medicinal mushroom), Babchi seed (Psoralea corylifolia L) . snake needle grass (Hedyotis diffusa), Curcuma kwangsiensis, Scorpion, Centipede and Rhubarb
17 Progression-free survival, a.k.a. PFS, is the length of time during and after treatment in which a patient continues to live with the cancer but it does not become worse.
18 The agents vemurafenib and dabrafenib, used for treating a skin cancer known as melanoma, carries the risk of developing another skin cancer (squamous cell carcinoma) later after treatment.