Chemotherapy Side-Effects/Risks

Chemotherapy is used primarily to treat people with cancer, although certain chemotherapy drugs have other functions.

Many chemotherapy drugs can cause diarrhea, lack of appetite, vomiting, and damage to the gastrointestinal tract. It makes sense for people undergoing chemotherapy to take a high-potency multivitamin/mineral, to protect against deficiencies.

Often, people who undergo chemotherapy develop aversions to certain foods, sometimes making it permanently difficult to eat those foods. Exposing people to what researchers have called a “scapegoat stimulus” just before the administration of chemotherapy can direct the food aversion to the “scapegoat” food instead of more important parts of the diet. In one trial, fruit drinks administered just before chemotherapy were most effective in protecting against aversions to other foods.

 


Signs, symptoms & indicators of Chemotherapy Side-Effects/Risks

Symptoms - Nails  

Black/brown fingernails

Black line(s) across the nails are common in dark-skinned persons but may also be the result of injury or chemotherapy.




Conditions that suggest Chemotherapy Side-Effects/Risks

Circulation  

Anemia, Megaloblastic

Some chemotherapy agents are known inhibitors of folic acid enzymes and as such can induce a megaloblastic anemia.



Digestion  


The Immune System  


Lab Values  

Low White Count

Radiation therapy and chemotherapy destroy fast-growing cells such as white blood cells. Patients receiving a combination of radiation therapy and chemotherapy are at greater risk of a low white count.




Risk factors for Chemotherapy Side-Effects/Risks

Metabolic  

Problem Caused By Being Underweight

As a general principle, when weight loss has occurred or is significant prior to the start of chemotherapy, the survival rate is reduced. The prognostic effect of weight loss prior to chemotherapy was analyzed using data from over 3000 patients enrolled in 12 chemotherapy protocols. The frequency of weight loss ranged from 31% for favorable non-Hodgkin’s lymphoma to 87% for gastric cancer. Median survival was significantly shorter in 9 protocols for the patients with weight loss compared to those without weight loss.



Symptoms - Cancer  

Considering chemotherapy or considering chemo/radiation



 

Recent/past chemotherapy use



Counter Indicators
Symptoms - Cancer  

No history of chemotherapy




Chemotherapy Side-Effects/Risks can lead to

Circulation  

Anemia, Megaloblastic

Some chemotherapy agents are known inhibitors of folic acid enzymes and as such can induce a megaloblastic anemia.



Digestion  


The Immune System  



Recommendations for Chemotherapy Side-Effects/Risks

Amino Acid / Protein  

Glutamine

In high doses, glutamine helps prevent the devastating damage to the gastrointestinal tract that results from chemotherapy.



 

L-Carnitine

Treatment with L-carnitine for 7 days at 4gm per day ameliorated chemotherapy-induced fatigue until the next cycle of

chemotherapy in a study of 50 patients who received cisplatin or ifosfamide. [Br J Cancer 2002;86(12): pp.1854-1857]



Botanical  

Ginseng, Korean - Chinese / Asian (Panax ginseng)

The use of Asian ginseng provides a protective effect from the stress of drug and radiation therapies.



 

Grapefruit / Citrus Seed Extract

August 9th, 2012. A glass a day of grapefruit juice lets patients derive the same benefits from an anti-cancer drug as they would get from more than three times as much of the drug by itself, according to a new clinical trial. The combination could help patients avoid side effects associated with high doses of the drug and reduce the cost of the medication.

Researchers at the University of Chicago Medicine study the effects that foods can have on the uptake and elimination of drugs used for cancer treatment. In a study published in August in Clinical Cancer Research, they show that eight ounces a day of grapefruit juice can slow the body’s metabolism of a drug called sirolimus, which has been approved for transplant patients but may also help many people with cancer.

Patients who drank eight ounces a day of grapefruit juice increased their sirolimus levels by 350%. A drug called ketoconazole that also slows drug metabolism increased sirolimus levels by 500%.

“Grapefruit juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs,” said study director Ezra Cohen, MD, a cancer specialist at the University of Chicago Medicine, “but this has long been considered an overdose hazard. Instead, we wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus.”

Grapefruit juice’s pharmaceutical prowess stems from its ability to inhibit enzymes in the intestine that break down sirolimus and several other drugs. The effect begins within a few hours of what the researchers refer to as “grapefruit juice administration.” It wears off gradually over a few days.

Cohen and colleagues organized three simultaneous phase-1 trials of sirolimus. Patients received only sirolimus, sirolimus plus ketoconazole, or sirolimus plus grapefruit juice. They enrolled 138 patients with incurable cancer and no known effective therapy.

The first patients started with very low sirolimus doses, but the amounts increased as the study went on, to see how much of the drug was required in each setting to reach targeted levels, so that patients got the greatest anti-cancer effect with the least side effects.

The optimal cancer-fighting dose for those taking sirolimus was about 90mg per week. At doses above 45mg, however, the drug caused serious gastrointestinal problems, such as nausea and diarrhea, so patients taking sirolimus alone switched to 45mg twice a week.

The optimal doses for the other two groups were much lower. Patients taking sirolimus plus ketoconazole, needed only 16mg per week to maintain the same levels of drug in the blood. Those taking sirolimus plus grapefruit juice, needed between 25 and 35mg of sirolimus per week.

“This is the first cancer study to harness this drug-food interaction,” the authors note.

No patients in the study had a complete response, but about 30 percent of patients in the three trials had stable disease, meaning a period when their cancers did not advance. One patient receiving grapefruit juice had a partial response – significant tumor shrinkage – that lasted for more than three years.

Although ketoconazole produced a slightly stronger drug-retention effect, grapefruit juice has the advantage that it is non-toxic, with no risk of overdose. “Therefore,” the authors wrote, “we have at our disposal an agent that can markedly increase bioavailability (in this study by approximately 350%) and, critically in the current environment, decrease prescription drug spending on many agents metabolized by P450 enzymes.”

Sirolimus was the first of a series of drugs, known as mTOR inhibitors, that were developed to prevent rejection of transplanted organs but that also have anti-cancer effects. As the first of its class, it was also the first to come off patent, making it less costly. “Further cost savings,” the authors suggest, could be realized “by combining the drug with agents that inhibit its metabolism.”

Because different people produce varied amounts of the enzymes that break down sirolimus, the effect of grapefruit juice can vary, but tests of enzyme levels may be able to predict how an individual patient will respond.

“The variation in potency of the grapefruit juice itself may be far greater than the variation in the enzymes that break down sirolimus,” Cohen said. An early version of the study used canned grapefruit juice, generously donated by a Chicago-based grocery chain. But tests of the product found it lacked the active ingredients. So the researchers shifted to a frozen concentrate product supplied by the Florida Department of Citrus. [Article adapted by Medical News Today from original press release.]



 

Medicinal Mushrooms

The mushroom Coriolus versicolor contains an immune-stimulating substance called polysaccharide krestin, or PSK. PSK has been shown in several studies to help cancer patients undergoing chemotherapy. One study involved women with estrogen receptor-negative breast cancer. PSK combined with chemotherapy significantly prolonged survival time compared with chemotherapy alone. [Cancer 1992;70: pp.2475–83] Another study followed women with breast cancer who were given chemotherapy with or without PSK. The PSK-plus-chemotherapy group had a 25% better chance of survival after ten years compared with those taking chemotherapy without PSK.[Anticancer Res 1995;15: pp.2907–12] Another study looked at people who had surgically removed colon cancer. They were given chemotherapy with or without PSK. Those given PSK had a longer disease-free period and longer survival time. PSK has also been reported to prevent the toxic effects of some chemotherapy agents (vincristine, cyclophosphamide, and Adriamycin) on blood cells in patients with breast cancer. [Dis Colon Rectum 1992;35: pp.123–30] Three grams of PSK were taken orally each day in these studies.

Although PSK is available without prescription in the United States, it is usually not found in health food stores. Through special suppliers to the medical profession, however, PSK can be obtained from doctors of natural medicine. Most but not all Coriolus versicolor extracts contain less than the high level of active ingredient (at least 30% protein-bound polysaccharides) found in PSK.



 


 

Astragalus Root (Astragalus membrinaceus)

Astragalus reduces bone marrow supression and gastrointestinal toxicity caused by chemotherapy and radiation. Research has also shown that subjects with advanced cancer showed a two to three fold increase in the strength of their immune response after being given astragalus. A second study showed that astragalus boosted immune response, even in animals that were treated with an immunosuppressive drug, cyclophosphamide. Astragalus is taken in China by cancer patients to boost immunity after drug or radiation treatment.



 

Coneflower (Echinacea purpura)

Echinacea is a popular immune-boosting herb that has been investigated for use with chemotherapy. One study looked at the effects of cyclophosphamide, echinacea, and thymus gland extracts to treat advanced cancer patients. Although small and uncontrolled, this trial suggested that the combination modestly extended the life span of some patients with inoperable cancers. Signs of restoration of immune function were seen in these patients. [Cancer Invest 1992;10: pp.343-48]



Nutrient  

Beta-Carotene

Chemotherapy frequently causes mouth sores. In one trial, people were given approximately 400,000 IU of beta-carotene per day for three weeks and then 125,000 IU per day for an additional four weeks. Those taking beta-carotene still suffered mouth sores, but the mouth sores developed later and tended to be less severe than mouth sores that formed in people receiving the same chemotherapy without beta-carotene.



Vitamins  

Antioxidants

A number of people have been concerned about the possible interference of antioxidants with chemotherapy and radiation effectiveness. A large formal review of the medical literature was done by Drs Lamson and Brignall, both Naturopathic Doctors and published in Alternative Medicine Reviews, 1999;4(5): pp.304-329. The results showed that there were actually only 3 specific chemotherpy treatments that interfered with the conventional chemotherapy, usually they actually helped. Their conclusion follows.

“Frequently, the effects of using antioxidants concurrent with chemotherapy and radiation are synergistic. Except for three specific interactions outlined above (flavonoids with tamoxifen, NAC with doxorubicin, and beta-carotene with 5-fluorouracil), there is no evidence to date showing that natural antioxidants interfere with conventional cancer therapeutics in vivo. Studies have shown patients treated with antioxidants, with or without chemotherapy and radiation, have many benefits. Patients have been noted to tolerate standard treatment better, experience less weight loss, have a better quality of life, and most importantly, live longer than patients receiving no supplements. It is time to research the role of these agents in conventional oncologic treatment, rather than dismiss them as a class based on theoretical concerns.”

Taking ACES (Vitamin A, Vitamin C, Vitamin E and selenium) before and during therapy has been helpful in decreasing the toxicity of chemotherapy, while increasing its effectiveness.

Applying vitamin E topically to mouth sores twice per day leads to complete healing in six out of nine people, compared with only one of nine taking placebo. Applying vitamin E only once per day was helpful to only some groups of patients in another trial, but not all studies have found vitamin E to be effective.



Key

Weak or unproven link
Strong or generally accepted link
Proven definite or direct link
Very strongly or absolutely counter-indicative
May do some good
Likely to help

Glossary

Chemotherapy

A treatment of disease by any chemicals. Used most often to refer to the chemical treatments used to combat cancer cells.

Cancer

Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.

Diarrhea

Excessive discharge of contents of bowel.

Gastrointestinal

Pertaining to the stomach, small and large intestines, colon, rectum, liver, pancreas, and gallbladder.

Mineral

Plays a vital role in regulating many body functions. They act as catalysts in nerve response, muscle contraction and the metabolism of nutrients in foods. They regulate electrolyte balance and hormonal production, and they strengthen skeletal structures.

Folic Acid

A B-complex vitamin that functions along with vitamin B-12 and vitamin C in the utilization of proteins. It has an essential role in the formation of heme (the iron containing protein in hemoglobin necessary for the formation of red blood cells) and DNA. Folic acid is essential during pregnancy to prevent neural tubular defects in the developing fetus.

Enzymes

Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.

Anemia

A condition resulting from an unusually low number of red blood cells or too little hemoglobin in the red blood cells. The most common type is iron-deficiency anemia in which the red blood cells are reduced in size and number, and hemoglobin levels are low. Clinical symptoms include shortness of breath, lethargy and heart palpitations.

White Blood Cell

(WBC): A blood cell that does not contain hemoglobin: a blood corpuscle responsible for maintaining the body's immune surveillance system against invasion by foreign substances such as viruses or bacteria. White cells become specifically programmed against foreign invaders and work to inactivate and rid the body of a foreign substance. Also known as a leukocyte.

Lymphoma

Any tumor of the lymphatic tissues.

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