Source: M. D. Anderson News Release 03/03/08
For most Americans, meals tend to center around meat. To significantly decrease a person’s risks of developing colorectal cancer,

experts at The University of Texas M. D. Anderson Cancer Center suggest a new approach to meal planning that focuses more on fruit and vegetable dishes.

According to recent findings issued by the American Institute for Cancer Research (AICR), consuming more than 18 ounces, or a little over a pound, of

red meat (pork, beef, lamb and goat) each week can significantly increase a person’s risks for developing colorectal cancer. In addition, every ounce and

a half of red meat a person eats over 18 ounces increases their risks by 15 percent.

March is Colorectal Cancer Awareness Month and National Nutrition Month, and nutritionists at M. D. Anderson Cancer Center are encouraging

people to increase portion sizes of the vegetable, fruit, whole grain and/or bean dishes being served and decrease the portion size of meat.

Focus on Fruit and Vegetable Dishes

Instead of asking what goes well with pork chops, ask what goes well with broccoli and sweet potatoes,said Sally Scroggs, senior health education specialist

in M. D. Anderson’s Cancer Prevention Center. That way, your serving of meat becomes more of a side dish and not the center of the meal.
Red meat contains substances linked to colon cancer,Scroggs said.For example, some studies suggest that the heme iron (the compound that gives red meat its color)

may increase the risk of developing colon cancer.

AICR recommends that two-thirds of a meal consist of plant-based foods. Consuming less red meat and more plant-based foods can significantly decrease

a person’s risks of developing colorectal cancer.

Don’t Eliminate Red Meat

Scroggs emphasizes that these recommendations are not meant to encourage people to completely eliminate red meat from their diet. Consuming red meat in modest amounts is a valuable source of nutrients, including protein, iron, zinc and vitamin B12. Moderation is the key,Scroggs said.

According to the United States Department of Agriculture, Americans were eating an average of 36 ounces of red meat every week in 2006, Scroggs said.

Scroggs recommends serving about three ounces (about the size of a deck of cards) of cooked red meat at meals. If you follow this recommended serving size,

you can include red meat in as many as six meals of your weekly diet.

Avoid Processed Meats

AICR also recommends eating very little processed meat (meat preserved by smoking, curing, salting or adding chemical preservatives), such as ham, bacon,

hot dogs, sausages, pastrami and salami. Every ounce and a half of processed meat eaten a day is thought to increase a person’s risks of developing colorectal cancer by 21 percent.

“A good idea to avoid eating processed meats as much as possible,Scroggs said.”Save that hot dog for special occasions, such as a family cookout or the ballpark.”

Colorectal cancer is the third most common cancer found in men and women in this country. The American Cancer Society estimates almost 150,000 new cases of colorectal cancer in the United States for 2008. Colorectal cancer is the second leading cause of cancer death among Americans but is considered a highly preventable disease.

Preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

For more than 30 years now, Chinese herbs and materials derived from the herbs, such as long chain polysaccharides, have been used as adjunct therapies for cancer patients. This modern application was first developed clinically in China and Japan during the 1970s and was relayed to the rest of the world in 1983 through an international conference in Beijing which was followed up by press reports in English and other languages (see: Physiological responses to immunologically active polysaccharides). The Institute for Traditional Medicine (ITM) made an effort to alert practitioners of Chinese medicine in the U.S. to this promising role for Chinese herbs immediately after that conference, with updated information provided as available over the years. The utilization of Chinese roots, leaves, and fruits (e.g., astragalus, gynostemma, ligustrum, and lycium), and several mushrooms (e.g., coriolus, ganoderma, cordyceps, and lentinus) for cancer patients is now a routine procedure when these patients visit acupuncturists, naturopathic physicians, and others offering adjunctive cancer health care.

Within the past couple of years, however, an increasing number of patients have been told by their oncologists to avoid herbs, and to more generally avoid supplements (such as vitamins), or, even more broadly, simply avoid anything with antioxidant potential while they are undergoing cancer therapies. The admonition itself is difficult to interpret, since all foods contain antioxidants and vitamins, and they also contain most of the other substances offered in dietary supplements. Most fruits, vegetables, beans, and nuts differ only slightly from herbs. A more specific recommendation is needed. But first, the question arises: why are doctors giving these instructions? What kind of information is being released to the public?

I have attempted to trace back the origins of the restrictions imposed by some oncologists, and it seems that the primary instigator of the concern was Dr. David Golde at the Memorial Sloan-Kettering Cancer Center, even though he was not the first to raise the matter (but within a few months of being first). The main issue he raised was the use of high doses of vitamin C, a therapy that has nothing directly to do with herbs. Herbs usually have little or no vitamin C; still, vitamin C is commonly prescribed or recommended as a supplement by practitioners involved in natural healing.

In a June 19, 2000 report of WebMD Medical News, the use of high doses of vitamin C to prevent heart disease, cancer, and other disorders, was called into question, and Dr. Golde’s research and comments were relayed (1, 2):

The first of two recent studies that called this notion [of taking high doses of vitamin C as a disease preventive] into question was carried out by David Golde, MD, physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York City, and described at an American Cancer Society meeting in March 2000. Golde and his colleagues transplanted human cancer cells into mice, injected the mice with vitamin C, and then measured the amount of the vitamin in the cells. They found that cancer cells seem to soak up large amounts of vitamin C by converting it into a form that’s easier to absorb. The results, Golde says, raise the possibility that cancer cells may use vitamin C to shield themselves against radiation and chemotherapy.

The second study, performed by James Dwyer, Ph.D., an epidemiologist at the University of Southern California, caused an even bigger stir. Dwyer told an American Heart Association meeting in March 2000 that middle-aged men who took 500 milligrams of vitamin C supplements daily showed a rapid narrowing of their carotid arteries, which supply blood to the brain.

The studies sound alarming, but experts warn against making too much of them. While Golde says that cancer patients shouldn’t take large doses of the vitamin, other researchers say it’s far too early to make that recommendation. There’s no evidence yet that C actually shields cancer cells from treatment, says Mark Levine, MD, an endocrinologist and Vitamin C expert at the National Institutes of Health. The cancers tested in Golde’s research, he says, may simply have grown from tissues that normally take in large amounts of the vitamin.

As for the heart disease finding, Dwyer himself cautioned that it is preliminary. The study lasted only 18 months and included just 573 men. And Robert Jacob, Ph.D., a research chemist with the U.S. Department of Agriculture, points out that previous studies suggested just the opposite-that vitamin C reduces the narrowing of carotid arteries.

From these very modest beginnings in Spring of 2000, the worry about antioxidants and cancer therapies grew, despite several warnings about the interpretation of data, such as those mentioned in the above analysis, and almost everyone who wished to provide a basis for the antioxidant and vitamin worry seemed to harken back to Dr. Golde’s very preliminary research. A pharmacist, John Russo, Jr., wrote the following to caution his readers about the possible interaction of antioxidants with brachytherapy (radiation therapy where the radiation source is placed inside the body) for prostate cancer (3):

How might an antioxidant adversely affect brachytherapy?
The precise role that the antioxidant, vitamin C, plays in tumors is not known, but recent studies have shown possible interactions between dietary antioxidants and cancer treatment.

We know that vitamin C is a powerful antioxidant. It consumes free radicals, the toxic substances in the body that can be generated by chemotherapy agents to destroy cancer cells. “It is possible,” according to Dr. David Golde, Physician-in-Chief at Memorial Sloan-Kettering Cancer Center, “that taking large amounts of vitamin C could interfere with the effects of chemotherapy or even radiation therapy.” These therapies often kill cells, in part, by using oxidative mechanisms. it’s conceivable then, that vitamin C might make cancer treatment less effective, and it is reasonable that cancer patients undergoing chemotherapy avoid taking large amounts of this vitamin.”

Building on past research
Earlier research by Dr. Golde and his colleagues established that specific glucose transporter molecules carry vitamin C into cells. This occurs once vitamin C, which is used by cells in the form of ascorbic acid, is converted into dehydroascorbic acid and transported into the cell. Once inside, the vitamin is converted back to ascorbic acid.

Applying this information to patient care
According to David Agus, an oncologist at Memorial Sloan-Kettering Cancer Center, we now know that tumors acquire and retain large amounts of vitamin C. And their nutritional needs appear to be similar to healthy cells that take in large amounts of the vitamin.”

However, what cancer cells do with the vitamin C after it is absorbed is not known. This will have to be determined before guidelines for the complementary use of antioxidants during chemotherapy and radiation become established.

Furthermore, research from University of Tubingen, School of Medicine in Germany suggests caution in applying this knowledge to all antioxidants in all types of malignancies. Examination of the modulation of drug-induced cytotoxicity and clonogenic cell death of glioma cells by three structurally unrelated antioxidants revealed that these antioxidants inhibit acute cytotoxicity and clonogenic cell death induced by cisplatin. However, they had little effect on the toxicity of other cancer drugs including BCNU, doxorubicin, vincristine, cytarabine, or camptothecin.

In the discussion of brachytherapy, the pharmacist carries the implications over to chemotherapy agents, but mistakenly states that these function by producing free radicals. In general, this is not the case, and only applies to radiation (see explanation of mechanism, Appendix).

The research cited here about an inhibition of cisplatin therapy by antioxidants (but, notably, no effect of the tested antioxidants on several other chemotherapy drugs) was published in 1998 (4), and did not produce much interest at the time, nor has a follow-up report been published to date (end of 2002). Glioma cells (a type of brain cancer) are normally resistant to the effects of chemotherapy, and the authors were examining factors influencing this already poor response. They determined, in their study, that cisplatin did not rely on free-radical formation to damage glioma cells, so antioxidant activity working directly against cisplatin effects was not an issue. Rather, the substances tested in this in vitro study appeared to function by some other unknown mechanism.

By contrast, another platin drug, oxaliplatin, was used in a double-blind, placebo controlled clinical trial along with administration of the antioxidant glutathione (GSH; see Figure 1). The authors concluded (5): “This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.”

This is an important finding, because it had been proposed that cancer cells could become resistant to platin drugs (e.g., cisplatin and carboplatin; due to changes in the cancer cell membrane, where the resistance may be caused by the binding of platinum to intracellular thiols, such as glutathione. This possibility, based on in vitro studies, implies that the interaction between platinum and GSH could prevent the active compounds from reaching the DNA nucleus. It is unclear at this point, whether administering glutathione can be recommended (as is often done by proponents of its protective effects), but this substance does not appear to have any direct interference with oxaliplatin when used clinically based on the recent clinical trial. In vitro studies indicate that high intracellular glutathione levels protect cancer cells from the effects of chemotherapy, but this may not carry over to the clinical situation.

A related concern about chemotherapy drug resistance has been raised about using antioxidants with cyclophosphamide, a particularly toxic anticancer drug. When the literature was reviewed, it was found that, if anything, the substances were beneficial for patients on cyclophosphamide therapy. Here is the interaction caution about this drug as relayed in Healthnotes (6-10):

Interactions with Dietary Supplements

Antioxidants
Cyclophosphamide requires activation by the liver through a process called oxidation. In theory, antioxidant nutrients (vitamin A, vitamin E, beta-carotene and others) might interfere with the activation of cyclophosphamide. There is no published research linking antioxidant vitamins to reduced cyclophosphamide effectiveness in cancer treatment. In a study of mice with vitamin A deficiency, vitamin A supplementation enhanced the anticancer action of cyclophosphamide. Another animal research report indicated that vitamin C may increase the effectiveness of cyclophosphamide without producing new side effects. Preliminary human research found that adding antioxidants (beta-carotene, vitamin A, and vitamin E) to cyclophosphamide therapy increased the survival of people with small-cell lung cancer treated with cyclophosphamide. It is too early to know if adding antioxidants to cyclophosphamide for cancer treatment is better than cyclophosphamide alone. Vitamin A can be toxic in high amounts. Intravenous injections of the antioxidant, glutathione, may protect the bladder from damage caused by cyclophosphamide. Preliminary evidence suggests, but cannot confirm, a protective action of glutathione in the bladders of people on cyclophosphamide therapy. There is no evidence that glutathione taken by mouth has the same benefits.

As reported here, when laboratory animal and clinical evaluation is the basis for the information, the potential benefits of antioxidants appear. One could say that there has been some backlash at the anti-antioxidant stance promoted by those who quote Dr. Golde and extend his vitamin C research to imply that all antioxidants are problematic for cancer patients. At the Rush Presbyterian St. Luke’s Medical Center, the suggestion that vitamin E might inhibit radiation effects was discounted. A press report stated (11):

Vitamin E Does Not Protect Cancer Cells Against Radiation

New York. 15 January 2000 (posted 19 March, 2001). Cancer patients who take vitamin E are probably not hindering the desired effects of radiation, according to a laboratory study done by radiation oncologists at Rush-Presbyterian-St. Luke’s Medical Center in Chicago.

Researchers at Rush were concerned that patients who take vitamin E may be inadvertently providing protection for the cancer cells that are the target of radiation therapy. Radiation damage is one form of oxidation, and vitamin E’s antioxidant properties presumably extend to cancer cells.

To determine if this were true, Rush researchers, led by Dr. Ed Blazek, director of radiation biology in the Rush department of radiation oncology, grew cells originating from human breast and prostate tumors in nutrient solutions containing several concentrations of vitamin E. The cells were then irradiated with the same daily doses used for patients.

The Rush team found that the tested concentrations of vitamin E did not interfere with the desired killing of cancer cells by radiation. An important limitation of this study, however, is that the level of vitamin E taken up by the cancer cells in laboratory culture has not yet been measured, and might be smaller than the level taken up by cells of a tumor in the patient’s body. If so, it is still possible that vitamin E might worsen treatment outcomes.

Although no undesirable protection of cancer cells was found, the researchers issued a caution to those taking vitamin E and other alternative therapies. “Any drug that is taken during cancer radiotherapy or chemotherapy should be tested to prove that it does not protect the tumor cells, defeating the intended effect of the treatment,” Blazek said.

Natural extensions of this work would include the addition of the drug pentoxifylline to vitamin E, since this combination has been reported to partially reverse radiation damage to normal tissue, the testing of vitamin C for radioprotection, and the testing of both vitamins E and C for protection from representative cancer chemotherapy drugs.

This research, performed by Drs. Alex Perez and Katherine Baker together with Dr. Blazek, was presented at the annual meeting of the Radiological Society of North America in Chicago.

Then, in a follow-up report from the same hospital, this time including vitamin C (12, 13):

Vitamins C and E Fight Side Effects of Pelvic Radiation for Cancer

March 20, 2001. A small study of 20 men and women suffering from chronic radiation proctitis has shown that daily vitamins E and C substantially reduced or eliminated their symptoms. Proctitis has traditionally been treated with anti-inflammatory agents, without satisfactory results.

Radiation therapy is one treatment option for men with localized prostate cancer and for women with cervix and endometrial cancers. Radiation therapy is effective in killing cancer cells. But the therapy damages also any normal, non-cancerous cells within range of the beam.

Complications are especially common in patients who are treated with older equipment. New, 3D conformal, Intensity Modulated or Proton beam equipment (available in the USA and some other countries) targets the beam much more precisely. Higher doses can be given to tumor with less damage to bladder and rectum.

Most patients take vitamins-does this interfere with killing cancer cells?

Even under the best conditions patients want to do everything possible to protect themselves from radiotherapy side effects. Many patients who undergo cancer treatments take vitamins and supplements. Until recently, oncologists seldom asked patients about this.

Doctors still have almost no evidence on which to advice cancer patients about common supplements. But a previous, laboratory study by radiation oncologists at Rush-Presbyterian-St. Luke’s Medical Center found that “Cancer patients who take vitamin E are probably not hindering the desired effects of radiation.”

Dr. Keith Bruninga, gastroenterologist at Rush-Presbyterian-St. Luke’s has now looked to see how much protection vitamins E and C actually offer patients irradiated for prostate, cervical or endometrial cancer. The effect of the vitamins in the treatment of chronic radiation proctitis had not been studied before, Dr. Bruninga said.

In normal bowel and rectal tissues exposed to radiation for cancer in the pelvis, oxygen radicals form and patients experience the symptoms of proctitis, he said. The condition starts with swollen, inflamed tissue, and it increases with dose. The symptoms, which may include diarrhea, pain, bleeding and incontinence, usually clear up within a few weeks of the last radiation treatment.

However, the symptoms do not clear up in 10-20 percent of patients. Some patients develop symptoms months or years after the initial radiation exposure.

“Our study showed that we can harness the potent antioxidant properties of the vitamins to repair cell damage and bring relief to many people who suffer from the persistent, lifestyle-altering symptoms of chronic radiation proctitis,” Dr. Bruninga says in a paper published in the April issue of The American Journal of Gastroenterology.

Oxygen free radicals form from cells that have been injured. Oxygen free radicals are highly active molecules that react with cells by changing or damaging their structure. The formation of the oxygen free radicals increases the amount of injury to the cells and results in a chronic condition as blood flow to the cells is decreased.

Vitamin E is a potent antioxidant that can react with damaging oxygen free radicals. Vitamin C in combination with E increases the effects of vitamin E. The researchers believe that the antioxidant treatment regimen using the vitamins counteracts and can prevent oxygen free radical injury and increase blood flow to the injured cells of patients with chronic radiation proctitis.

Patients in the study, ten men and ten women with chronic radiation proctitis, took one 400 IU vitamin E tablet along with one 500 mg vitamin C tablet three times each day for eight consecutive weeks. Patients purchased the vitamins themselves at the store of their choice.

Each patient in the study rated their symptoms in terms of severity and frequency before and after treatment with the vitamins using a questionnaire developed by the researchers.

The impact of the symptoms on the lifestyle of the patients was also assessed using a questionnaire. Ten of the patients were assessed again after one year to determine if their initial responses were sustained.

The assessments showed a significant improvement in bleeding, diarrhea and urgency after taking the vitamins. Patients with rectal pain did not improve significantly. Thirteen patients reported an improvement in their lifestyle including seven whom reported a complete return to normal.

All of the ten patients who were assessed after one year reported a sustained improvement in their symptoms while continuing to take the vitamins.

The Rush physicians believe that the actual incidence of the ailment is greater than the estimated 10-20 percent of radiation patients. They feel that many patients, relieved and grateful that their cancers are remission, are embarrassed to tell their physicians about the symptoms of radiation proctitis.

Currently, the Rush physicians are seeking additional individuals with chronic radiation proctitis to conduct a larger, double-blinded study of the effectiveness of antioxidants in the treatment of the illness.

“If our continued research shows that the antioxidant regimen is successful in treatment of this illness, we plan to investigate its use to prevent chronic radiation proctitis,” said Dr. Bruninga.

Results of the study appear in April 2002 issue of The American Journal of Gastroenterology.

THE ALTERNATIVE: AVOIDING EVEN NORMAL LEVELS OF ANTIOXIDANT INTAKE

One of the early complaints about vitamins and chemotherapy was this one, described just four months before Dr. Golde made his comments at an American Cancer Society Meeting, summarized by a report on prostate cancer (13):

Vitamins and Chemotherapy

Although the antioxidant vitamins A, C, and E help repair damaged cells, it is probably not a good idea to take large amounts during radiation treatment. One object of chemotherapy is to damage cancer cells. Antioxidants, however, appear to counteract the process, according to Dr. Rudolph Salganik’s report to the annual meeting of the American Society for Cell Biology (December 1999). He pointed out that “Almost all anticancer drugs kill cancer cells by way of apoptosis, and antioxidants like vitamin A and vitamin E dramatically reduce apoptosis in cancer cells.” Patients should therefore avoid taking any more than a normal amount of these vitamins during chemotherapy treatment.

This sounds like reasonable advice-just don’t add to normal intake-but Dr. Salganik’s own suggestion went further: indicating that an antioxidant-depleted diet could improve cancer therapies. The study referred to above was reported on as follows (14):

Study: avoiding vitamins A, E might improve cancer therapy

By David Williamson, UNC-CH News Services

CHAPEL HILL-Vitamins A and E, which normally boost human health in numerous ways, also appear to keep cancer cells from dying through the natural protective process scientists call apoptosis, new University of North Carolina at Chapel Hill research shows.

As a result, giving patients those vitamins may prevent cancer cells from self-destructing and work against cancer therapy, scientists say.

Researchers at UNC-CH’s schools of public health and medicine presented their findings Monday (Dec. 13) during a news conference at the American Society for Cell Biology’s annual meeting in Washington, D.C. Drs. Rudolph Salganik, research professor of nutrition, and Terry Van Dyke, professor of biochemistry and biophysics, directed the studies.

“We believe this work is important because it may make cancer treatments more effective,” Salganik said. “It suggests that cancer patients, especially those undergoing chemotherapy or radiation therapy, may do better on an antioxidant-depleted diet.”

The scientist and his colleagues study reactive oxygen species (ROS), which play a central role in the series of signals that allow cells to kill bacteria and viruses, destroy toxins and trigger the apoptotic “suicide” of defective cells such as cancer, he said. Antioxidants, such as vitamins A and E, protect normal cells from the damaging effects of ROS but apparently also can prevent the targeted apoptotic death of cancer cells that threaten humans and other mammals, the new work suggests.

Other researchers involved were Drs. Craig D. Albright, research assistant professor of nutrition; and Steven H. Zeisel, professor of nutrition and pediatrics and chair of nutrition.

The UNC-CH experiments involved putting mice that were predisposed to developing brain tumors on specially modified diets that were either supplemented with standard amounts of antioxidants or were antioxidant deficient for four months. Researchers then carefully monitored the rodents’ health and their brain tumors, if any, to see how the animals fared on the different diets.

Mice receiving extra vitamins A and E showed no benefit in either the size or incidence of brain tumors, Salganik said. They also had relatively short lives.

“Interestingly and more importantly, in animals that received antioxidant-depleted diets, brain tumors were significantly reduced in size because of induction of oxidant stress due to what are commonly called free radicals in the brain tumors,” Albright said. “Higher levels of cell death was restricted only to the brain tumors, while normal tissues were not affected by depletion of antioxidants in the mouse diets.”

In mice getting low levels of vitamins A and E, no negative effects were seen in normal cells, but about 19 percent of tumor cells showed evidence of apoptosis. In those ingesting normal quantities of antioxidant vitamins, only about 3 percent of tumor cells were apoptotic.

The group’s findings may explain two previous clinical studies showing that heavy smokers who ate a diet high in beta-carotene antioxidants had significantly higher rates of lung cancer, Salganik said.

“These new studies raise important issues regarding the advisability of ingesting high levels of antioxidants as a potential anti-cancer benefit,” Albright said. “Clearly, more studies are needed at the clinical level in human populations to address the real value of antioxidant supplements or antioxidant depletion in people at risk of developing cancer.”

Salganik said he hoped clinical studies would begin within a year or two. Van Dyke is a member of the UNC Lineberger Comprehensive Cancer Center.

Up to this point, no clinical study results along these lines have been reported. The suggestion of starving antioxidants, however, runs contrary to most of the information currently available. The study referred to above, involving heavy smokers and beta-carotene intake has already been the subject of considerable controversy and it appears there were unique factors in this population of heavy smokers in Finland that were studied. Findings to the contrary are common. For example, in a recent evaluation of the risks of lung cancer in relation to various carotenoids ingested. The conclusion was (15):

Lower risks of lung cancer were observed for the highest versus the lowest quintiles of lycopene (28%), lutein/zeaxanthin (17%), beta-cryptoxanthin (15%), total carotenoids (16%), serum beta-carotene (19%), and serum retinol (27%). These findings suggest that high fruit and vegetable consumption, particularly a diet rich in carotenoids, tomatoes, and tomato-based products, may reduce the risk of lung cancer.

SHOULD HERBS BE WORRISOME ADJUNCTS TO CANCER THERAPIES?

There is only one herb that has been implicated in a potential adverse effect on chemotherapy, and its effect has nothing to do with antioxidant activity of the herb. This one herb has been implicated in lowering the dose of a wide range of drugs because it strongly activates the drug-metabolizing enzyme cytochrome P450 CYP3A4. This is St. John’s wort (16), which was commonly used for treating depression during the 1990s, but has since become little used due to the concerns for drug interactions (as well as some question about its efficacy). No other herb has been identified as a potential inhibitor of chemotherapy drugs. Although many herbs have some antioxidant potential, their influence over oxidative reactions is low due to the low dosage commonly employed. Unlike vitamin C, which is presented as a pure or nearly pure compound in dietary supplements, herbs contain little vitamin C (in relation to Dr. Golde’s concern) and low levels of antioxidant substances. Further they contain little, if any, of the substances that appeared to inhibit cisplatin cytotoxicity in cultured glioma cells. There are no pharmacology or clinical studies showing problems with herbs other than St. John’s wort in relation to chemotherapy or radiation therapy. By contrast, the widespread use of herbs and herb extracts to minimize cancer therapy side effects in the Orient is accompanied by extensive favorable reports.

REASONABLE PHYSICIAN’S ADVICE

Cautions that can reasonably be forwarded by physicians are these:

1. The use of herbs and dietary supplements, including vitamins and antioxidants, as adjuncts to modern cancer therapies, is an area of ongoing research and, at this time, little is known about the clinical effects.
2. Concerns have been raised about use of antioxidants, mainly high doses of vitamin C and high doses of glutathione, based on laboratory experiments suggesting that these substances might impair the full effect of cancer therapies. Clinical studies have not yet revealed any adverse effects, but the concern persists on a theoretical basis, backed up by the laboratory reports; there are also laboratory and clinical reports that suggest that vitamin C and glutathione have positive effects in relation to cancer therapies.
3. There is a wide range of recommendations for patient actions based on interpretations of the data available so far. These range from recommendations to administer herbs, vitamins, and other supplements to reduce the adverse effects of cancer therapies without impairing the benefits of the cancer therapies, to maintaining normal healthy dietary recommendations without adding anything, to specifically avoiding antioxidant substances, including those that are normally present in a healthy diet.
4. Most medical experts agree that one should not pursue high doses of nutritional supplements or herbs because not enough is known about their potential impact on cancer therapies; their purported benefits may not be confirmed, while there could be risks. However, the only substances for which a strong caution has been repeated are St. John’s wort, which may lower the dose of chemotherapy drugs in the body (no impact on radiation therapy is expected), high doses of vitamin C, which might have some protective effect for cancer cells during the therapy, and the antioxidant glutathione, which if taken continuously in large dose might aid cancer cell drug resistance.

In making these comments, physicians should recognize that a wide range of therapies are offered to patients and that the meaning of “high dose” or “continuous use” may vary. For example, physicians should recognize that some proponents of high dose vitamin C therapy recommend huge doses of the vitamin specifically for purported anti-cancer effects. The amounts involved are difficult to consume in one day (e.g., orally consumed up to bowel tolerance, which is typically in the range of 6-12 grams per day). Indeed, some have recommended a continuous vitamin C intravenous drip (8 hours a day) to try inhibiting cancers that are resistant to standard medical therapies (this is after chemotherapy has been suspended). Such huge doses of vitamin C are unproven for effectiveness and could conceivably reduce the impact of concurrent cancer therapies by a number of mechanisms because very high blood levels are attained.

However, most nutritional supplements that involve high doses of vitamin C provide less than 2 grams of the vitamin each day, usually spread over 2 to 3 doses. Blood levels do not rise very much by oral administration, as the vitamin is absorbed gradually and excreted within hours. There is no evidence that these amounts of oral vitamin C would be harmful for cancer patients. Most proponents of nutritional supplementation, relying upon extensive reports on vitamin C, currently recommend doses of 500-1,500 mg/day. Patients could be cautioned to limit their intake of this particular vitamin to no more than that range.

It is important to note that if cancer cells have a mechanism for absorbing large amounts of vitamin C, and if this is helpful to the growth of cancer cells or to protect against anti-cancer therapies, the amount of vitamin C available in the body normally (baseline of about 60 micromoles/liter) should be sufficient to satisfy the cancer’s appetite for it.

Aside from the projected problems with high-dose vitamin C (Dr. Golde did not show inhibition of cancer therapies, only high uptake of vitamin C by cancer cells), there simply is no evidence that other antioxidants (except possibly glutathione), nutritional supplements, or herbs (except St John’s wort) inhibit cancer therapies or worsen overall outcomes. To the contrary, they appear to improve outcomes. In the case of St. John’s wort, this herb was not proposed as either a treatment for cancer nor a treatment for cancer therapy side effects; rather, it has been used incidentally in the treatment of depression. Thus, no herbs intentionally used as adjuncts to cancer therapy have been implicated in adverse effects clinically.

Even in the case of glutathione, there is reason to believe this substance is not problematic in clinical practice. A concern was raised earlier about supplementation with glutamine, an amino acid that is used to produce glutathione in the body and which is considered a “glutathione-sparing” agent: as glutamine levels increase, glutathione levels are maintained at high levels. Several studies have indicated that glutamine might be a valuable aid to cancer patients, recommended to prevent neuropathy from high dose chemotherapy, to protect the heart from damage due to doxorubicin therapy, and to protect the bowel from damage due to radiation or chemotherapy, but the concern was raised that it would also benefit cancer cells. The studies conducted to date do not support a negative effect for glutamine in relation to cancer. To the contrary, glutamine appears to improve the retention of the chemotherapy drug methotrexate by tumor cells. In one report on this subject, it was concluded that: “These data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury.” The mechanism of action was proposed to be the increase in cellular glutathione related to elevated glutamine levels (18). Dr. VS Klimberg, of the Department of Pharmacology, University of Arkansas, has been a leading researcher in the use of glutamine as a protective agent for cancer patients and has reported widely on its effects. Glutamine and glutathione are currently recommended by many who advocate the use of adjunctive cancer therapies.

Physicians who wish to approach the issue with the most conservative viewpoint could caution patients about extreme therapies, with multiple high dose antioxidants, but cannot with any clinical evidence argue against moderate use of herbs, vitamins, or antioxidants. In fact, the evidence, limited as it may be, is that moderate use of antioxidants is a reasonable approach for patients who are concerned about chemotherapy side effects.

In a recent review of the subject, Kedar Presad and colleagues at the Center for Vitamin and Cancer Research, Department of Radiology, Health Sciences Center, University of Colorado, described the differing views and, as a summary, they pointed out (19):

Radiation therapy is one of the major treatment modalities in the management of human cancer. While impressive progress like more accurate dosimetry and more precise methods of radiation targeting to tumor tissue has been made, the value of radiation therapy in tumor control may have reached a plateau. At present, two opposing hypotheses regarding the use of antioxidants during radiation therapy have been proposed. One hypothesis states that supplementation with high doses of multiple micronutrients including high dose dietary antioxidants (vitamins C and E, and carotenoids) may improve the efficacy of radiation therapy by increasing tumor response and decreasing some of its toxicity on normal cells. The other hypothesis suggests that antioxidants (dietary or endogenously made) should not be used during radiation therapy, because they would protect cancer cells against radiation damage. Each of these hypotheses is based on different conceptual frameworks that are derived from results obtained from specific experimental designs, and thus, each may be correct within its parameters. The question arises whether any of these concepts and experimental designs can be used during radiation therapy to improve the management of human cancer by this modality.

Based on the review of literature, the authors concluded that vitamin C, vitamin E, carotene, and other antioxidants could be useful as a safe adjunct to radiation therapy. Matt Brignall, of the Seattle Cancer Treatment and Wellness Center, where adjunctive therapies are emphasized, also pointed to the evidence supporting the benefit of antioxidants during cancer therapy, saying (20):

Critics of the concurrent use of antioxidants and chemotherapy often point to the lack of clinical trials in humans. Previous preliminary clinical trials, however, have concluded that the antioxidants ginkgo (Ginkgo biloba), melatonin, coenzyme Q10, and N-acetylcysteine did not appreciably reduce the effect of cancer therapies. Pharmaceutical antioxidants, such as amifostine and mesna, have also been extensively studied in conjunction with chemotherapy and radiation, and have not appeared to cause a negative interaction. Many prominent cancer scientists believe that the dietary and pharmaceutical antioxidants prevent some of the worst side effects of cancer treatments.

Further, a common antioxidant now recommended to cancer patients is green tea, which contains an amino acid (theanine) that appears to help retain doxorubicin and other chemotherapy drugs within cancer cells (21). Thus, while it can be reasonable for physicians to offer some limited cautions about use of herbs, vitamins, and antioxidants, they must also be careful not to warn people away from potentially usefully adjunct therapies.

December 2002

REFERENCES

1. Leslie M, Vitamin C: How much do you really need?, WebMDHealth, June 19, 2000.
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APPENDIX 1. BASIC UNDERSTANDING OF THE CANCER THERAPIES

The precise mechanisms of cancer therapies are not fully worked out, though considerable information is available. The following is an overview, based on the author’s understanding, indicating the potential role of herbs, vitamins, and antioxidants in preventing side effects of cancer therapies without impairing anticancer treatment.

Radiation

Standard external radiation therapy pinpoints a beam of intensely energetic photons (x-rays, gamma-rays or beta-rays) to a tumor site . The radiation dose at the focal point is lethal to the cells. Some of the radiation directly breaks up cellular DNA and other components in the target area; it is estimated that about one-third of the damage is direct destruction of critical molecules, leading to inability of the cell to reproduce or to prompt cell death. The primary damage to the tumor, however, comes from generation of a huge number of free radicals that interact with cellular components and disrupt them. These free radicals are mostly generated from water, because it is the most abundant substance in the cells. Because of the beam intensity at the focal point, no amount of antioxidant activity from orally ingested supplements is likely to be able to save these cells.

External radiation therapy is usually administered over an extended period, with several treatments spaced out with many days interval between. The reason that the whole task is not performed with one treatment is that the collateral damage from the radiation would be so severe as to threaten the patient’s survival. As it is, when the beam enters the body on its way to the tumor site and exits beyond the tumor, and spreads a bit on either side of the target, the collateral damage is notable and can be extreme. The skin becomes burned and delicate internal organs can become severely damaged and almost unusable. For example, radiation to the throat area can make swallowing virtually impossible; abdominal radiation can cause intestinal ulceration that doesn’t heal for months if at all. Still, these off-target tissues are able to repair somewhat between the treatments thanks to the more limited damage at these sites compared to at the tumor itself. As the distance from the beam’s focal point increases, there is greater chance to protect the cells with antioxidants that are able to handle the small number of free radicals that are generated.

There are other types of radiation therapy, including brachytherapy, in which radioactive material is inserted into the tumor (as commonly employed for prostate cancer): the radiation spreads out around radioactive “seeds” and kills all cells in the surrounding area, with reduced damage the greater the distance from the radiation source. There are now proton and neutron beams that have a higher proportion of damage caused by direct strikes at DNA and other cellular components, with less reliance on free radical generation.

It is a desired outcome that the collateral damage from all radiation techniques be minimized, which is a potential valuable role for antioxidants. The chances of antioxidants protecting the tumor cells are minimal; there is simply too much radiation at the target. Failures of radiation therapy are mostly attributable to metastasis of the cancer cells (before radiation begins) rather than failure of the radiation to destroy every cancer cell at the target tumor site. No amount of antioxidant therapy nor the reverse-complete avoidance of antioxidant therapy during radiotherapy-will have an impact on this metastasis that has occurred before radiation therapy. Metastatic cells can not be detected by current means and may not reveal themselves for months or even years, which is why cancer therapies are not considered a true success until 5 years pass without sign of new tumor growth, usually at a different site.

One cannot know for certain what effect-good or bad-antioxidants will have on the effects of radiation therapy, without extensive clinical testing that may take years. The concept that tumor cells can be protected is largely based on the assumption that antioxidants are extremely efficient. They would have to clean up the reactive oxygen species as fast as they are produced. Yet, the very large amount of antioxidant research conducted over the past decade clearly shows that these substances have limited impact for several diseases. Where they were thought to have the potential to treat diseases, they have not been very successful, and where they are thought to prevent diseases, they appear effective so long as the exposure to the antioxidants is for years and years, having a continuous mild impact. Antioxidants can be expected to provide some aid to cells unintentionally caught in the periphery of radiation therapy, but, even there, complete protection is not expected due to limited effects.

Chemotherapy

As with radiation therapy, chemotherapy is administered over an extended period, often (though not always), with a duration of several days or weeks between treatments. As with radiation therapy, the task cannot be accomplished all at once, because a lethal chemotherapy dose for the entire tumor would also be lethal for the patient. In fact, one of the key measures of the patient’s ability to continue chemotherapy is recovery of the white blood cell count that has been impaired by the drug therapy (this does not apply to some of the new immune based and genetic therapies). Chemotherapy is usually not as focused as radiation therapy on the tumor, and affects the entire body (commonly causing hair loss, distress of the gastro-intestinal system, white blood cell depletion, and fatigue). An adjunctive treatment that protects non-target cells (normal cells) might also protect cancer cells. However, as occurs with radiation therapy, there is a difference between the intensity of the drug action on cancer cells and on other cells, such as bone marrow cells. Otherwise, once the cancer was destroyed successfully, the bone marrow would also be destroyed (which is, in fact, one of the radical chemotherapy approaches, but not the first line treatment). Chemotherapy drugs are selected for clinical use on the basis that they have a more potent action on cancer cells than on other cells. Thus, after the cancer is destroyed, hair grows back, digestion returns to normal, and the immune system functions fully once again. Protection that helps the bone marrow does not necessarily have the potency to protect the cancer cells. Failure of chemotherapy is often the result of the presence of some resting cells, usually cells outside the active tumor mass, that do not respond to chemotherapy drugs. The drugs usually interact with replicating DNA and might miss such individual metastatic cells that are quiescent.

Polysaccharides from herbs have been used for protecting the bone marrow in cancer patients undergoing chemotherapy in China, Japan, and other countries for many years. The clinical study reports indicate improved outcomes (better survival) in patients who utilize this adjunct therapy. It can be argued that the study methodology is inadequate to support the improved survival, and it can be argued that the valid outcomes might be clinically insignificant, so that there is little or no interest in pursing this approach here. But, there is no evidence that bone marrow protection leads to negative effects in terms of tumor destruction or survival rates.

A positive role for antioxidants in the case of chemotherapy drugs is protection against a variety of undesired secondary effects, particularly neuropathy and cardiac damage. The chemotherapy drugs do not function as oxidants, but, rather, influence the cellular DNA and RNA. Except in one in vitro study cited above for glioma cells that are normally resistant to chemotherapy, there is no evidence that antioxidants worsen the outcome of cancer chemotherapies. To the contrary, there is some evidence of protection for secondary effects. Dr. Golde’s in vitro research on vitamin C did not show that this substance impaired cancer therapies, only that cancer cells seem to “soak up” the vitamin. His results may not translate to an impairment of the effects of radiation therapy or chemotherapy.

The essential factor in both radiation therapy and chemotherapy is the specificity of the treatment for cancer cells. Antioxidants, herbs, and other kinds of natural supplements are being applied to protect cells that are unintentionally damaged by cancer therapy where the damage is substantially less severe than that caused to the cancer cells. The ability to provide protection for non-target cells without interfering with the damage to cancer cells is based largely on the differential. One may expect that where a cancer therapy is equally lethal to target and non-target cells, that a therapy protective of the non-target cells might also be protective of the target cells. Despite the apparent protection offered by antioxidants and herbs to non-target cells, their abilities to provide that protection are limited. Patients still experience side effects; they are only reduced in intensity. The ability of these same substances to protect target cells is far less, which explains why there hasn’t been a sudden failure of cancer therapies during the past decade when millions of people have turned to routine use of supplements with vitamin C, vitamin E, and other antioxidants.

ScienceDaily (Nov. 17, 2007) — Natural HIV-1 infection does not always elicit a protective immune response, according to a new study.

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A team of researchers from Washington University, the Fred Hutchinson Cancer Research Center of Seattle, and the University of Nairobi show how HIV-1 vaccines may not be as reliable against superinfection as once thought.

Superinfection of HIV-1 occurs when an individual infected with one strain of HIV-1 acquires a second strain. Currently there are over 20 published cases of HIV-1 superinfection, most of which have been focused on individuals who have been carefully monitored during their infection. These cases prove that an HIV-1 vaccine may not always protect against infection by a different strain. But because there have been reports of selected individuals, it has been unclear how commonly HIV-1 re-infection occurs.

To address this question, Dr. Julie Overbaugh and her research team investigated the incidence of HIV-1 superinfection in 36 high-risk women followed roughly five years after their initial infection.

Seven cases of superinfection were found; five of them occurring over a year past initial infection. Additionally, three of the seven cases displayed a virus from the same HIV-1 genetic subtype.

This study suggests that immune responses found in natural HIV-1 infection, which fail to provide protection against re-infection, may not be the best path to an effective HIV-1 vaccine.

Journal article: Piantadosi A, Chohan B, Chohan V, McClelland RS, Overbaugh J (2007) Chronic HIV-1 infection frequently fails to protect against superinfection. PLoS Pathog 3(11):e177. doi:10.1371/journal.ppat.0030177

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Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

Fatigue from chemotherapy can range from a mild to extreme feeling of being tired. Many people describe fatigue as feeling weak, weary, worn out, heavy, or slow. Resting does not always help.

Many people say they feel fatigue during chemotherapy and even for weeks or months after treatment is over. Fatigue can be caused by the type of chemotherapy, the effort of making frequent visits to the doctor, or feelings such as stress, anxiety, and depression. If you receive radiation therapy along with chemotherapy, your fatigue may be more severe.

Fatigue can also be caused by

• Anemia
• Pain
• Medications
• Appetite changes
• Trouble sleeping
• Lack of activity
• Trouble breathing
• Infection
• Doing too much at one time
• Other medical problems

Fatigue can happen all at once or little by little. People feel fatigue in different ways. You may feel more or less fatigue than someone else who gets the same type of chemotherapy.

Ways to manage

• Relax. You might want to try meditation, prayer, yoga, guided imagery, visualization, or other ways to relax and decrease stress.
• Eat and drink well. Often, this means 5 to 6 small meals and snacks rather than 3 large meals. Keep foods around that are easy to fix, such as canned soups, frozen meals, yogurt, and cottage cheese. Drink plenty of fluids each day–about 8 cups of water or juice.

Plan time to rest. You may feel better when you rest or take a short nap during the day. Many people say that it helps to rest for just 10 to 15 minutes rather than nap for a long time. If you nap, try to sleep for less than 1 hour. Keeping naps short will help you sleep better at night.

• Be active. Research shows that exercise can ease fatigue and help you sleep better at night. Try going for a 15-minute walk, doing yoga, or riding an exercise bike. Plan to be active when you have the most energy. Talk with your doctor or nurse about ways you can be active while getting chemotherapy.
• Try not to do too much. With fatigue, you may not have enough energy to do all the things you want to do. Choose the activities you want to do and let someone else help with the others. Try quiet activities, such as reading, knitting, or learning a new language on tape.

Sleep at least 8 hours each night. This may be more sleep than you needed before chemotherapy. You are likely to sleep better at night when you are active during the day. You may also find it helpful to relax before going to bed. For instance, you might read a book, work on a jigsaw puzzle, listen to music, or do other quiet hobbies.

• Plan a work schedule that works for you. Fatigue may affect the amount of energy you have for your job. You may feel well enough to work your full schedule. Or you may need to work less–maybe just a few hours a day or a few days each week. If your job allows, you may want to talk with your boss about ways to work from home. Or you may want to go on medical leave (stop working for a while) while getting chemotherapy.
• Let others help. Ask family members and friends to help when you feel fatigue. Perhaps they can help with household chores or drive you to and from doctor’s visits. They might also help by shopping for food and cooking meals for you to eat now or freeze for later.
• Learn from others who have cancer. People who have cancer can help by sharing ways that they manage fatigue. One way to meet others is by joining a support group–either in person or online. Talk with your doctor or nurse to learn more.

• Try not to do too much. With fatigue, you may not have enough energy to do all the things you want to do. Choose the activities you want to do and let someone else help with the others. Try quiet activities, such as reading, knitting, or learning a new language on tape.

• Keep a diary of how you feel each day. This will help you plan how to best use your time. Share your diary with your nurse. Let your doctor or nurse know if you notice changes in your energy level, whether you have lots of energy or are very tired.
• Talk with your doctor or nurse. Your doctor may prescribe medication that can help decrease fatigue, give you a sense of well-being, and increase your appetite. He or she may also suggest treatment if your fatigue is from anemia.

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ScienceDaily (Jul. 26, 2007) — Cancer patients who receive a drug that stimulates the growth of infection-fighting white blood cells may be significantly less likely to die from a chemotherapy-related complication characterized by fever and low white blood cell levels, according to a multi-institutional study led by researchers from the University of Rochester School of Medicine and Dentistry and the Duke Comprehensive Cancer Center.

“Chemotherapy drugs target cancer cells, but they can affect healthy cells as well, including infection-fighting white blood cells,” said Nicole M. Kuderer, M.D., a hematology-oncology fellow at Duke and lead author on the publication. “When patients’ white blood cell counts drop too low, they are at risk for dangerous infections that can cause death.”

Often, chemotherapy must be delayed, reduced in strength or halted when a patient’s white blood cell count is too low, potentially leading to poorer outcomes, she added.

“Patients taking a drug known as granulocyte colony-stimulating factor early in their chemotherapy were about half as likely to develop dangerously low white blood cell counts with fever, and half as likely to die from infection,” Kuderer said. “This study represents an important part of the effort to better treat this common complication in cancer patients receiving chemotherapy.”

The researchers published their findings in the July 20, 2007 issue of the Journal of Clinical Oncology. The work was part of research being conducted by the Awareness of Neutropenia in Chemotherapy (ANC) Study Group, a multi-institution, university-based network of investigators whose work is unrestrictedly funded by Amgen, the maker of a commonly utilized white blood cell booster that goes by the names Neupogen and Neulasta. Kuderer also receives funding from the National Institutes of Health.

This study compiled the results of 17 trials involving more than 3,000 patients receiving chemotherapy of varying intensity to treat several different types of cancers. The researchers found that nearly 40 percent of the patients who did not receive the white blood cell booster early in treatment developed the fever and low white blood cell levels called febrile neutropenia, compared to only 22 percent of the patients who took the drug in conjunction with their chemotherapy, Kuderer said.

While white blood cell boosters were known to help patients receiving very intense doses of chemotherapy, this study showed that the drugs are also a benefit to cancer patients receiving more common chemotherapy doses, Kuderer said.

Recently revised American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Center Network (NCCN) guidelines for the use of drugs such as Neulasta and Neupogen align with the conclusions reached by this study.

“The new guidelines recommend using these types of drugs when at-risk patients begin chemotherapy, rather than waiting for complications to develop,” said Jeffrey Crawford, M.D., chief of the division of medical oncology at Duke and one of the study’s investigators. “The new recommendations also suggest that we need better methods to identify patients who are at higher risk of developing febrile neutropenia, and future studies will be aimed at doing just that.”

White blood cell boosters can have side effects, including bone pain, which need to be reviewed and discussed with each patient, Crawford said.

Other investigators on the study include Gary Lyman of Duke and David Dale of the University of Washington.

Duke University Medical Center (2007, July 26). White Blood Cell Booster May Help Cancer Patients Avoid Deadly Complications. ScienceDaily. Retrieved December 4, 2007, from http://www.sciencedaily.com­ /releases/2007/07/070725110020.htm

ScienceDaily (Apr. 27, 2007) — A University of Nebraska Medical Center study has found that even before women with breast cancer undergo chemotherapy, they experience fatigue and disruptions in sleep and activity levels. Researchers say their findings suggest health professionals should address fatigue following breast cancer surgery.

Researchers say controlling fatigue after surgery — before starting chemotherapy — is important because fatigue typically increases during chemotherapy. Between 70 to 95 percent of breast cancer patients experience fatigue while undergoing chemotherapy.

The study was published in the current issue of the Journal of Pain and Symptom Management. Having studied 130 women with early stage breast cancer (stage I, II, IIIA), it the largest study to document the prevalence of fatigue associated with altered sleep and activity patterns before chemotherapy treatment. The data confirms what was reported in a previous smaller study funded by the National Institutes of Health.

“We found women are not going into chemotherapy in the best possible shape,” said Ann Berger, Ph.D., Niedfelt Professor of Nursing, UNMC College of Nursing, who has conducted several studies over the past 15 years related to fatigue in cancer patients. “It makes it that much more difficult to reduce the fatigue during treatment. If you start out with some fatigue, it will probably increase.”

“We as health professionals need to address potential fatigue and sleep issues sooner,” said Dr. Berger, principal investigator of the study. “If women are having sleep problems after surgery, we need to address this symptom before women begin chemotherapy. “What we’ve learned might explain why we’re having problems reducing fatigue in breast cancer patients during chemotherapy.”

The published study comes from initial results of a five-year, $1.5 million grant Dr. Berger and her team received in 2003. The purpose of the study, which was funded by the National Institute of Nursing Research, a division of the National Institutes of Health, was to determine the best ways to reduce fatigue during chemotherapy and to prevent chronic fatigue after treatment.

Researchers measured sleep and activity patterns during the 48 hours prior to the first chemotherapy treatment using wristwatch-sized activity monitors called actigraphs.

Fatigue, the most prevalent and distressing symptom for breast cancer patients receiving chemotherapy, has long been accepted by health professionals and patients alike as a side effect of treatment. Researchers say there are ways to intervene, and now they have found it may be important to intervene during the recovery period after breast cancer surgery.

Researchers say disrupted sleep, low daytime activity and/or reduced activity are likely to contribute to mild fatigue before chemotherapy and moderate to severe fatigue after chemo. They say fatigue should be addressed before and after surgery. Women typically begin chemotherapy three to four weeks after surgery.

Dr. Berger said because inactivity contributes to fatigue, she and colleagues say though women need to rest for several days after surgery, they should try to regain activity when they’re able. “We’ve been telling patients for years to rest and take it easy, but in some cases, we’re finding the patients who remain inactive are the one who report higher fatigue.”

Cancer-related fatigue can have a profound impact on an individual’s life, with significant physical, emotional, social, and economic consequences that may persist for months or years after completing treatment. Even after treatment ends, between 30 and 50 percent of patients say their fatigue remains at least six months or doesn’t ever go away.

Fatigue related to cancer treatment is described as a distressing, persistent, sense of tiredness or exhaustion that is not proportional to activity. The factors associated with fatigue are the presence and severity of anxiety, pain, lower sleep quality, physical inactivity, and poor performance status, leaving little desire to work or socialize.

Dr. Berger said the findings provide an important benchmark to begin looking for interventions to reduce cancer-related fatigue.

The study was undertaken to further establish values for sleep, wake, activity, rest, circadian rhythms and fatigue and how they interrelate in women before and during the first year after chemotherapy.

University Of Nebraska (2007, April 27). Fatigue Affects Breast Cancer Patients Even Before First Chemotherapy Treatment, According To Study. ScienceDaily. Retrieved December 4, 2007, from http://www.sciencedaily.com­ /releases/2007/04/070426135536.htm

Antioxidants May Aid Chemotherapy Patients

Science Daily (Apr. 27, 2007) — There is no evidence that antioxidant supplements interfere with the therapeutic effects of chemotherapy agents, according to a recent systematic review of the use of antioxidants during chemotherapy, available in the May, 2007 issue of the peer-reviewed journal Cancer Treatment Reviews. In fact, they may help increase survival rates, tumor response, and the patient’s ability to tolerate treatment.

This conclusion has important implications for patients whose oncologists discourage the use of antioxidant supplements during treatment. Until now, their concern has been that these supplements may counteract the tumor-shrinking abilities of the chemotherapy.

“This review demonstrates that there is no scientific support for the blanket objection to using antioxidants during chemotherapy. In addition, it also appears that these supplements may help mitigate the side effects of chemotherapy,” said Keith I. Block, MD, lead author of the study and Medical Director of the Block Center for Integrative Cancer Treatment. “This is significant because it increases the likelihood that patients will be able to complete their treatment.”

Co-author Dr. Robert Newman, Professor of Cancer Medicine at M. D. Anderson Cancer Center said, “This study, along with the evolving understanding of antioxidant-chemotherapy interactions, suggests that the previously held beliefs about interference do not pertain to clinical treatment.”

The analysis, titled “Impact of Antioxidant Supplementation on Chemotherapeutic Efficacy: A Systematic Review of the Evidence from Randomized Controlled Trials,” evaluated 845 articles from five scientific databases that examined the effects of taking natural antioxidant supplements concurrent with chemotherapy.

Out of the 845 studies that were analyzed, 19 met all evaluation criteria. These included the use of randomized trials with a control group, and the reporting of treatment response (tumor shrinkage) and survival data. The 1,554 patients represented had a variety of cancer types, and most had advanced or relapsed disease. Some of the antioxidants used in the trials included glutathione, vitamin A, vitamin C, vitamin E, ellagic acid, selenium and beta carotene.

Among the findings:

• All of the studies that included survival data showed similar or better survival rates for the antioxidant group than the control group.
• None of the trials supported the theory that antioxidant supplements diminish the effectiveness of chemotherapy treatments.
• All but one of the studies that reported treatment response showed similar or better response in the antioxidant group than in the control group.
• 15 of 17 trials that assessed chemotherapy toxicities, including diarrhea, weight loss, nerve damage and low blood counts, concluded that the antioxidant group suffered similar or lower rates of these side effects than the control group.

The authors noted that reducing side effects may help patients avoid having to cut back on their chemotherapy dosing, interrupt scheduled treatments, or abandon treatment altogether. This in turn, is likely to favorably impact treatment outcomes. A recent study of a group of colon cancer patients indicated that those who completed their full prescribed schedules of chemotherapy had survival rates nearly double those of patients who abandoned their chemotherapy treatment prematurely.

This new study encourages further exploration of the potential importance of antioxidant supplements as a means of improving cancer survival.

Block Center for Integrative Cancer Treatment (2007, April 27). Antioxidants May Aid Chemotherapy Patients. Science Daily.

By-Jane Gross

Published: April 29, 2007

On an Internet chat room popular with breast cancer survivors, one thread — called “Where’s My Remote?” — turns the mental fog known as chemo brain into a stand-up comedy act.

Michael Houghton for The New York Times

When she can’t remember where she parked her car, Lu Ann Hudson uses a key fob that sets off a beep in it.

Narayan Mahon for The New York Times

“I had a mind like a steel trap, and I ended up with a colander for a brain,” said Linda Lowen, who underwent chemotherapy 13 years ago.

Bob Hewitt for The New York Times

Terry-Lynne Jordan leaves herself voice mail messages as reminders.

One woman reported finding five unopened gallons of milk in her refrigerator and having no memory of buying the first four. A second had to ask her husband which toothbrush belonged to her.

At a family celebration, one woman filled the water glasses with turkey gravy. Another could not remember how to carry over numbers when balancing the checkbook.

Once, women complaining of a constellation of symptoms after undergoing chemotherapy — including short-term memory loss, an inability to concentrate, difficulty retrieving words, trouble with multitasking and an overarching sense that they had lost their mental edge — were often sent home with a patronizing “There, there.”

But attitudes are changing as a result of a flurry of research and new attention to the after-effects of life-saving treatment. There is now widespread acknowledgment that patients with cognitive symptoms are not imagining things, and a growing number of oncologists are rushing to offer remedies, including stimulants commonly used for attention-deficit disorder and acupuncture.

“Until recently, oncologists would discount it, trivialize it, make patients feel it was all in their heads,” said Dr. Daniel Silverman, a cancer researcher at the University of California, Los Angeles, who studies the cognitive side effects of chemotherapy. “Now there’s enough literature, even if it’s controversial, that not mentioning it as a possibility is either ignorant or an evasion of professional duty.”

That shift matters to patients.

“Chemo brain is part of the language now, and just to have it acknowledged makes a difference,” said Anne Grant, 57, who owns a picture-framing business in New York City. Ms. Grant, who had high-dose chemotherapy and a bone marrow transplant in 1995, said she could not concentrate well enough to read, garbled her sentences and struggled with simple decisions like which socks to wear.

Virtually all cancer survivors who have had toxic treatments like chemotherapy experience short-term memory loss and difficulty concentrating during and shortly afterward, experts say. But a vast majority improve. About 15 percent, or roughly 360,000 of the nation’s 2.4 million female breast cancer survivors, the group that has dominated research on cognitive side effects, remain distracted years later, according to some experts. And nobody knows what distinguishes this 15 percent.

Most oncologists agree that the culprits include very high doses of chemotherapy, like those in anticipation of a bone marrow transplant; the combination of chemotherapy and supplementary hormonal treatments, like tamoxifen or aromatase inhibitors that lower the amount of estrogen in women who have cancers fueled by female horemones; and early-onset cancer that catapults women in their 30s and 40s into menopause.

Other clues come from studies too small to be considered definitive. One such study found a gene linked to Alzheimer’s disease in cancer survivors with cognitive deficits. Another, using PET scans, found unusual activity in the part of the brain that controls short-term recall.

The central puzzle of chemo brain is that many of the symptoms can occur for reasons other than chemotherapy.

Abrupt menopause, which often follows treatment, also leaves many women fuzzy-headed in a more extreme way than natural menopause, which unfolds slowly. Those cognitive issues are also features of depression and anxiety, which often accompany a cancer diagnosis. Similar effects are also caused by medications for nausea and pain.

Dr. Tim Ahles, one of the first American scientists to study cognitive side effects, acknowledges that studies have been too small and lacked adequate baseline data to isolate a cause.

“So many factors affect cognitive function, and the kinds of cognitive problems associated with cancer treatment can be caused by many other things than chemotherapy,” said Dr. Ahles, the director of neurocognitive research at Memorial Sloan-Kettering Cancer Center in New York.

The new interest in chemo brain is, in effect, a testimony to enormous strides in the field. Patients who once would have died now live long enough to have cognitive side effects, just as survivors of childhood leukemia did many years ago, forcing new treatment protocols to avoid learning disabilities.

“A large number of people are living long and normal lives,” said Dr. Patricia Ganz, an oncologist at U.C.L.A. who is one of the nation’s first specialists in the late side effects of treatment. “It’s no longer enough to cure them. We have to acknowledge the potential consequences and address them early on.”

As researchers look for a cause, cancer survivors are trying to figure out how to get through the day by sharing their experiences, and by tapping expertise increasingly being offered online by Web sites like www.breastcancer.org and www.cancercare.org.

There are “ask the experts” teleconferences, both live and archived, and fact sheets to download and show to a skeptical doctor. Message boards suggest sharpening the mind with Japanese sudoku puzzles or compensatory techniques devised to help victims of brain injury. There are even sweatshirts for sale saying “I Have Chemo Brain. What’s Your Excuse?”

Studies of cognitive effects have overwhelmingly been conducted among breast cancer patients because they represent, by far, the largest group of cancer survivors and because they tend to be sophisticated advocates, challenging doctors and volunteering for research.

Most researchers studying cognitive deficits say they believe that those most inclined to notice even subtle changes are high-achieving women juggling careers and families who are used to succeeding at both. They point to one study that found that complaints of cognitive deficits often did not match the results of neuro-psychological tests, suggesting that chemo brain is a subjective experience.

“They say, ‘I’ve lost my edge,’ ” said Dr. Stewart Fleishman, director of cancer supportive services at Beth Israel and St. Luke’s/Roosevelt hospitals in New York. “If they can’t push themselves to the limit, they feel impaired.”

Dr. Fleishman and others were pressed as to why a poor woman, working several jobs to feed her children, navigating the health care system and battling insurance companies, would not also need mental dexterity. “Maybe we’re just not asking them,” Dr. Fleishman said.

Overall, middle-class cancer patients tend to get more aggressive treatment, participate in support groups, enroll in studies and use the Internet for research and community more than poor and minority patients, experts say.

“The disparity plays out in all kinds of ways,” said Ellen Coleman, the associate executive director of CancerCare, which provides free support services. “They don’t approach their health care person because they don’t expect help.”

But approaching a doctor does not guarantee help. Susan Mitchell, 48, who does freelance research on economic trends, complained to her oncologist in Jackson, Miss., that her income had been halved since her breast cancer treatment last year because everything took longer for her to accomplish.

She said his reply was a shrug.

“They see their job as keeping us alive, and we appreciate that,” Ms. Mitchell said. “But it’s like everything else is a luxury. These are survivor issues, and they need to get used to the fact that lots of us are surviving.”

Among women like Ms. Mitchell, lost A.T.M. cards are as common as missing socks. Children arrive at birthday parties a week early. Wet clothes wind up in the freezer instead of the dryer. Prosthetic breasts and wigs are misplaced at the most inopportune times. And simple words disappear from memory: “The thing with numbers” will have to do for the word “calculator.”

Linda Lowen, 46, had a hysterectomy and chemotherapy for ovarian cancer 13 years ago, and says she still cannot recognize neighbors at the grocery store. “I had a mind like a steel trap, and I ended up with a colander for a brain,” said Ms. Lowen, a radio and television talk show host in Syracuse.

The other night, Ms. Lowen set out to find a good place to store her knitting supplies. She began emptying a cabinet of games that her teenage daughters no longer played. Meanwhile, she noticed a blown light bulb and went to find a replacement. That detour led to another, and five hours later she had scrubbed every surface and tidied the contents of eight drawers. But she still had no storage space for her knitting supplies.

“I have an almost childlike inability to follow through on anything,” Ms. Lowen said.

Solutions come in many forms for women whose cancer treatment has left them with cognitive deficits.

Sedra Jayne Varga, 50, an administrative assistant in family court in Manhattan, is part of a research study of the stimulant Focalin, which she said had helped. But Ms. Varga also plans to have laser surgery on her eyes so that losing her glasses will no longer be an issue.

Lu Ann Hudson, 44, a designer of financial databases in Cincinnati, relies on a key fob that sets off a beep in her car when she is looking for it in parking lots. Terry-Lynne Jordan, 43, who analyzes environmental incidents for an oil company in Calgary, Alberta, uses the calendar on her computer and voice mail messages to herself to remind her of meetings.

And Debbie Kamplain, a 32-year-old stay-at-home mother in Peoria, Ill., hired a $30-an-hour personal organizer to help her sell a house, buy another and get ready to move her family to Indiana next month.

But it is Ms. Kamplain’s 2 ½-year-old son, Daniel, who sees to it that she stays on task. Long before Daniel could talk, he would pull her over to the refrigerator if she got distracted while getting him a drink.

“Poor kid,” Ms. Kamplain said. “I say I’m going to do something, forget about it immediately, and he’s the one who has to remind Mommy about stuff.”