Cancer Radiation Therapy

Radiation therapy is given to about 60% of all cancer patients, but it can inflict significant damage on healthy normal tissues. Radiotherapy can also cause secondary cancers after the primary cancer has been treated, which typically occur several years later. Other secondary diseases such as pneumonitis and radiation fibrosis may also occur. Radiation therapy is associated with both acute and delayed disturbances in nutritional status.

Radiation therapy relies on the free radical disruption of cellular DNA. The rationale behind damaging cancer cell DNA is that it may preclude successful division into more cancer cells or trigger cancer cell apoptosis (also known as programmed cell death). Radiation therapy can be delivered from both external or internal sources, may be high or low dose, and is often delivered with computer-assisted accuracy to the site of the tumor. Brachytherapy (or interstitial radiation therapy) places the source of radiation directly into the tumor as temporarily implanted ribbons and seeds or as permanently implanted seeds.

Newer radiotherapy technologies, such as stereotactic radiosurgery, which uses tightly focused x-rays or gamma rays to target tumors without widespread irradiation of surrounding tissues, may improve radiotherapy results. However, these approaches are limited to certain types of cancers.

Cancer often outgrows the ability of the host to supply blood vessels and oxygen. Cancer cells are therefore often found in a low-oxygen (hypoxic) environment. Hypoxic cancer cells are radio-resistant, an effect that contributes significantly to the inability of radiotherapy to control large cancers. Therapies that provide more oxygen to cancer cells help radiation work more effectively by enabling more free-radical formation. Remember: Radiation kills cancer cells by concentrating massive amounts of free radicals directly into tumors. L-arginine is a promising natural agent for enhancing oxygenation of tumor cells due to its ability to increase the serum nitric oxide level, which enhances blood flow by expanding arterial elasticity. Enhanced blood flow provides more oxygen to tumors that in turn enables radiation therapy to generate more cell-killing free radicals.

Consuming 20-30 grams of arginine 30-60 minutes prior to each radiation session could significantly increase the number of cancer cells killed in persons undergoing radiation therapy. Many people find it difficult to consume 20-30 grams of arginine orally. As an alternative, a physician could administer the arginine via an IV (intravenous) infusion 30 minutes before each radiation session. Arginine is available to doctors in IV dosing packs for the purpose of testing pituitary growth hormone response. However, conventional physicians are reluctant to try innovative approaches. Patients seeking to use high dose arginine prior to each radiation session have the following options:

Swallowing 23-33 arginine (900 mg per capsule) capsules
Mixing 2.5-3.5 tablespoons of unpleasant-tasting arginine powder and drinking the mixture
Taking 4-6 tablespoons of an arginine-based drink called sugar-free PowerMaker II. (This makes normally unpalatable arginine acceptable to taste.)
Finding a physician in your area who will have trained a medical technician to administer the 20-30 grams of arginine by IV therapy prior to each radiation session.

To further saturate the tumor with more oxygen, some patients breathe pure oxygen during the radiation therapy (Kaanders et al. 2002; Zajusz et al. 1995; Evans et al. 1975)

Arginine will not be of much benefit if there is a deficiency in the ability of blood to carry oxygen (anemia). Anemia is common in cancer patients. Conventional cancer therapies, such as surgery, chemotherapy, radiation, and testosterone blockade, often induce anemia. Elevated levels of certain cytokines such as tumor necrosis factor-alpha (TNF-alpha), commonly seen in cancer patients, also suppress red blood cell formation.

The adverse effect of anemia in cancer patients is well established in scientific literature. A study conducted to systematically review the effect of anemia on survival in cancer patients found that the increased risk of mortality associated with anemia in cancer was an astounding 65% (Caro et al. 2001). Anemia is often associated with general malnutrition. Insurance companies refuse reimbursement for expensive antianemia drugs (Procrit) unless the patient is severely anemic (often 25% below the lowest number on the standard reference range). This means that cancer patients are denied access to potential life-saving drugs such as Procrit.

As already noted, in order to deliver more oxygen to the tumor, there has to be enough oxygen-carrying capacity in the blood. Indicators of oxygen-carrying capacity, such as hematocrit and hemoglobin, should be in the upper one-third range of normal prior to radiation therapy. There are nutrients that help improve anemic states, but as noted earlier, any cancer patient that is not in the upper one-third of normal should be prescribed Procrit or Epogen to naturally stimulate red blood cell production. R.A. Smith, M.D. (clinical radiation oncologist, practicing in Jackson, MS), has typically employed 1 gram of vitamin C 3 times daily and 400 IU of vitamin E daily in all patients receiving large radiation fields and has noticed regular increases in red blood cell count, white blood cell count, and platelets after such simple antioxidant intervention is initiated (Smith 2002).

Radiation Therapy. High energy rays, focused in on a beam, are used to damage the cancer cells and stop their reproduction. This local therapy is used to shrink a cancer's size either before surgical removal or after, to kill any remaining cancer cells. Side effects may range from minimal to moderate including: tiredness, skin rashes, and a decrease in infection-fighting white blood cells. (Anatomical Chart Company 2002?, Lippincott Williams & Wilkins)

Arginine functions to enhance blood flow to tumors, thereby increasing the cell-killing effects of radiation therapy. There are additional mechanisms by which arginine may benefit the cancer patient.

Nitric oxide is generated from L-arginine by the family of nitric oxide synthase enzymes. Nitric oxide is an important molecule involved in vascular homeostasis, immune regulation, and host defense. Large amounts of nitric oxide produced for relatively long periods of time (days to weeks) in macrophages and vascular endothelial cells after challenge with lipopolysaccharide or cytokines (such as interferons) are cytotoxic for various tumor cells. This cytotoxic effect against tumor cells was found to be associated with apoptosis.

The mechanism of nitric oxide-mediated apoptosis involves several factors, including the accumulation of the tumor suppressor protein p53, damage to mitochondrial functions, alterations in the expression of members of the Bcl-2 family, activation of the caspase cascade, and DNA fragmentation. Depending on the amount, duration, and the site of nitric oxide production, this molecule may not only mediate apoptosis in target cells, but also protect cells from apoptosis induced by other apoptotic stimuli (Umansky et al. 2001).

Additionally, when nitric oxide production was inhibited, there was a significant increase in capillary formation. However, when L-arginine was introduced, capillary formation returned to baseline values, thus halting tumor angiogenesis (Phillips et al. 2001).

All cells, both normal and cancerous, have molecular receptor sites on their surface. These sites are much like locks that may be opened or activated only by the correct molecular key. Once opened, a chain of biochemical events occurs specific to that receptor. Cytokine growth factors are a class of substances that stimulate cell growth by a variety of mechanisms, specific to the receptor site that they activate.

Radiation induces overexpression of certain receptor sites and cytokine growth factors as the cancer attempts to survive the radiation. This overexpression of cytokine growth factors, or signal transduction pathways, limits the effectiveness of radiation in causing the destruction of the cancer cells. These same pathways, when overexpressed, are implicated in tumor cells resistance to cytotoxic drugs. However, inhibition of these receptor sites, or pathways, effectively shuts down overexpression and the resistance of cancer cells to both chemotherapy and radiation.

The following natural products have been shown to be synergistic with chemotherapy and radiation, exhibiting signal transduction inhibitory effects. Specific dosing suggestions can be found in the Summary section of the protocol.

The Foundation previously recommended that soy extracts not be used 1 week prior to, during, and 1 week after undergoing radiation therapy, based on preliminary research. However, a number of new studies indicate that this view may have been incorrect. Indeed, far from inhibiting the impact of radiation on cancer cells, research shows that genistein, an isoflavone from soy, enhances the radio-sensitivity of cancer cells (Akimoto et al. 2001).

Radiation causes cancer cells to overexpress a survival signal transduction pathway called vascular endothelial growth factor (VEGF) by 2.81-fold (Ando et al. 2000). The epidermal growth factor receptor (EGFR), important in cancer cell proliferation, is also similarly enhanced (Dangles et al.1997), and there is a significant increase in intracellular glutathione levels, all in an apparent attempt to survive the radiation (Kojima et al. 2000).

Addition of genistein to cancer cell lines blocks the survival signal expressed by the cancer cells and elevates glutathione levels in a dose-dependent manner (Suzuki et al. 2002). The efficacy of radiation was strongly enhanced, suggesting genistein may be a therapeutic agent with a potent synergistic effect with radiation (Hillman et al. 2001).

Curcumin, an extract of the spice turmeric, is synergistic with genistein and may be effective in helping to suppress a number of escape mechanisms that are activated by radiation. These mechanisms of tumor suppression are:

Inhibition of nuclear factor kappa-beta (NF-kB), a transcription factor that many cancers over-express and use as a growth vehicle to escape cell regulatory control. Studies showed a 41% increase in radiosensitivity with NF-kB blockade (Plummer et al. 1999; Russo et al. 2001).
Inhibition of the EGFR site. One study noted 300% amplification in radiation-induced apoptosis with blockade of the EGFR (Dorai et al. 2000).
Inhibition of cyclooxygenase-2 (COX-2), the enzyme involved in the production of PGE-2, a tumor-promoting prostaglandin hormone. Studies noted an amplification in radiosensitivity of 1.9-fold with the selective inhibition of the COX-2 enzyme (Zhang et al. 1999; Pyo et al. 2001).

As previously noted radiation induces cancer cells to overexpress the survival signal transduction pathway VEGF 2.81-fold. VEGF is also considered essential for tumor angiogenesis. (Angiogenesis is the process of new blood vessel formation from surrounding tissue into a tumor.) Green tea through its catechin, EGCG, a tea polyphenol, blocks induction of VEGF. In vivo studies on green tea have shown the following actions on cancer cells (Jung et al. 2001a):

Caffeine occurs naturally in green tea and has been shown to potentiate the tea polyphenols (Dulloo et al. 2000). There are many published studies supporting the use of caffeine in the treatment of cancer (Saito et al. 2003; Mercadante et al. 2001). The caffeine in green tea has a synergistic effect improving green tea's anticarcinogenic capabilities. In SKH-1 mice at high risk for developing malignant and nonmalignant tumors, the oral administration of caffeine alone as their sole source of drinking fluid for 18-23 weeks was performed to ascertain the inhibitory effects of caffeine. The study revealed that caffeine inhibited the formation and decreased the size of both the nonmalignant and malignant tumors (Lou et al. 1999).

It is of interest that scientific research with caffeine lends credibility to the seemingly bizarre claims of the legendary Max Gerson, M.D., and others, who contend that coffee enemas were effective for cancer patients, especially patients with liver metastases (Gerson 1978). Caffeine has been found to improve pain relief when combined with narcotics and is found in several commonly used analgesics such as Empirin #3 (Tylenol #3) (Mercadante et al. 2001).

In cancer, p53 gene mutations are the most common genetic alterations observed (50-60%). Caffeine has been shown to potentiate the destruction of p53 defective cells by inhibiting its growth signal (G2). These effects inhibit and override the DNA-damage checkpoint and thus kill dividing cells. This ability by caffeine is important because the basis of many anticancer therapies is DNA damage destruction of the replicating cells. Caffeine uncouples cell-cycle progression by interfering with the replication and repair of DNA. Caffeine therefore serves as an agent that overrides DNA damage checkpoints that can be used to sensitize cells to the killing effects of DNA damaging drugs. This effect has been demonstrated by several research studies (Ribeiro et al. 1999; Blasina et al. 1999; Jiang et al. 2000; Valenzuela et al. 2000).

Additionally, caffeine potentiated radio-chemotherapy, sensitizing cells to the killing effects of genotoxic drugs (Tsuchiya et al. 2000). This was not the case after irradiation alone or caffeine treatment alone and was only induced by irradiation in combination with caffeine in cells with a mutant p53 gene via a p53-independent pathway (Higuchi et al. 2000). In addition, caffeine not only induced p53-independent arrest and enhanced radiation-induced apoptosis, but caffeine, in a dose-dependent manner, induced apoptosis independent of any other factors (Qi et al. 2002).

It may be more efficacious to take green tea in capsule form rather than a brewed beverage because 2 capsules exceed the phytochemical potency of 5 cups of freshly brewed green tea. An appropriate dose for VEGF-blockade would be five 350-mg capsules of a lightly caffeinated 95% green tea extract with each meal. Some people may want to use a decaffeinated green tea extract capsule toward the end of the day because 5 capsules of even lightly caffeinated green tea may be overstimulating.

Since decaffeinated green tea capsules contain 300 mg of green tea extract per capsule, 6 of these capsules should be taken during each daily interval. It is suggested that 95% green tea extract capsules be taken in 3 intervals throughout each day. A typical dose taken by a cancer patient could be 5 lightly caffeinated green tea capsules at breakfast, 5 at lunch, and 6 green tea decaffeinated capsules at dinner. Patients should be observed for agitation or overstimulation because some persons are easily stimulated by caffeine.

A new form of selenium called Se-methylselenocysteine (SeMSC) is a naturally occurring selenium compound found to be an effective agent in the prevention of cancer (Medina et al. 2001). SeMSC is a seleno-amino acid that is synthesized by plants such as garlic and broccoli. Based on its unique mechanisms of action, SeMSC could also benefit a cancer patient (Brown et al. 2001).

SeMSC induces apoptosis through caspase activation. Caspases are a class of cysteine proteases that includes several factors involved in apoptosis. Caspase participates in the molecular control of apoptosis by cleaving a subset of cellular proteins and thus dismantling the cell (Yeo et al. 2002). Additionally, SeMSC has been shown to be effective against mammary cell growth both in vivo and in vitro (Sinha et al. 1999) and has significant anticarcinogenic activity against mammary tumorigenesis (Sinha et al. 1997). Moreover, of the selenium compounds tested, SeMSC is one of the most effective chemopreventive forms (Jung et al. 2001b). Exposure to SeMSC blocks clonal expansion of premalignant lesions at an early stage. This is achieved by simultaneously modulating certain molecular pathways that are responsible for inhibiting cell proliferation and enhancing apoptosis (Ip et al. 2001). SeMSC has been shown to:

Unlike selenomethionine, which is incorporated into protein in place of methionine, SeMSC is not incorporated into any protein, thereby offering a completely bioavailable compound. In animal studies, SeMSC has been shown to be 10 times less toxic than any other known form of selenium. The recommended dose of Se-methylselenocysteine (SeMSC) is 200-400 mcg a day for cancer patients.

It has been found that cancer cells and normal cells respond differently to nutrients and drugs that affect glutathione status. The concentration of glutathione in tumor cells is higher than that of the normal cells that surround them. This difference in glutathione status between normal cells and cancer cells is believed to be an important factor in the resistance of cancer cells to chemotherapy (Fojo et al. 2003; Townsend et al. 2003). Whey protein concentrate has been shown to selectively deplete cancer cells of their glutathione, thus making them more susceptible to cancer treatments such as radiation and chemotherapy.

Tumor cell glutathione concentration may be among the determinants of the cytotoxicity of radiation. Rapid glutathione synthesis in tumor cells is associated with high rates of cellular proliferation. Depletion of cancer cell glutathione in vivo decreases the rate of cellular proliferation and inhibits cancer growth (Kennedy et al. 1995).

It is difficult to reduce glutathione sufficiently in tumor cells without placing healthy tissue at risk. A compound that can selectively deplete the cancer cells of their glutathione, while increasing or at least maintaining the levels of glutathione in healthy cells, such as whey protein, is efficacious (Bounous 2000; Tsai et al. 2000).

Cancer cells treated with whey proteins are depleted of their glutathione and their growth is inhibited, while normal cells have an increase in glutathione and increased cellular growth. These effects were not seen with other proteins. Selective depletion of tumor cell glutathione may render cancer cells more vulnerable to the action of radiation (Bravard et al. 2002) and meanwhile protect normal tissue from the deleterious effects of radiation (Savarese et al. 2003; Kennedy et al. 1995).

The exact mechanism by which whey protein achieves this is not fully understood, but it appears that it interferes with the normal feedback mechanism and regulation of glutathione in cancer cells. Glutathione production is inhibited by its own synthesis. Since baseline glutathione levels in cancer cells are higher than those of normal cells, it is probably easier to reach the level of negative-feedback inhibition with the cancer cells' glutathione levels than with the normal cells' glutathione levels.

Cancer patients undergoing radiation therapy may consider taking 30-60 grams a day of whey protein concentrate in divided doses, starting at least 10 days before beginning therapy, during therapy, and then continuing for at least 10 days after completion of the therapy.

Radiation-induced lung injury frequently limits the total dose of thoracic radiotherapy that can be delivered to a patient undergoing radiation therapy, limiting its effectiveness.

Supplemental vitamin A may reduce lung inflammation after thoracic radiation and be an important radio-protective agent in the lung of cancer patients as it is in animals (Redlich et al. 1998).

Researchers have also reported the radio-protective effect of beta-carotene from a study conducted on over 700 children exposed to radiation by the Chernobyl nuclear accident. Natural beta-carotene protected against the susceptibility of lipids to oxidation and may act as an in vivo lipophilic antioxidant or radioprotector. Patients undergoing radiotherapy should consider taking vitamin A 25,000 IU a day.

Caution: Vitamin A is one of the few vitamins with a well-recognized hypervitaminosis syndrome. See the vitamin A precautions in Appendix A: Avoiding Vitamin A Toxicity to avoid toxic overdose, particularly if multivitamins already contain large doses of vitamin A.

The amino acid taurine is severely depleted when people undergo radiation therapy. A possible therapeutic effect of taurine supplementation relative to radiation therapy has been suggested (Desai et al. 1992). Supplementing with 2000 mg a day of taurine is therefore recommended to people undergoing cancer radiation therapy.

Radiation requires the presence of oxygen to generate free radicals to kill tumor cells. It is well-established, however, that most human tumors are poorly oxygenated (hypoxic) because of blood perfusion and diffusion limitations (Vaupel et al. 2001), intermittent blood flow in the tumor microcirculation (Hill et al. 1996), and the occurrence of anemia in cancer patients (reduced hemoglobin indicates reduced oxygen levels) (Auclerc et al. 2003; Thomas et al. 2002). In fact, radiation therapy itself usually induces anemia, which is associated with a poor prognosis in cancer patients (Harrison et al. 2002). Melatonin stimulates platelet production (thrombopoiesis) (Lissoni et al. 2001) and has been shown to effectively treat cancer patients with low platelet counts and anemia (Lissoni et al. 1997).

Moreover, melatonin has an anti-serotonergic effect, which means that it may block the inhibition of blood flow by serotonin (Bubenik et al. 2002). This consequently may increase blood flow and allow restoration of the microcirculation, which is compromised in the tumor microenvironment (Vaupel et al. 2000). Melatonin may improve the blood supply to the tumor, increasing tumor oxygen levels and thus increasing radiation-induced tumor cell death (by overcoming radio-resistance) (Hockel et al. 1996).

In addition, melatonin is lipid soluble and can presumably cross the blood tumor barrier as it does the blood-brain-barrier (Bubenik et al. 1998). Melatonin may further increase the delivery of radiation to poorly oxygenated regions within the tumor microenvironment, consequently increasing the effectiveness of this anticancer treatment. Radiation, which frequently causes inflammation of the mucosa (mucositis), may substantially reduce melatonin levels in the body (Karbownik et al. 2000) by damaging the mucosa of the gastrointestinal tract where melatonin is known to be localized (Bubenik et al 2002).

Patients with brain glioblastoma generally experience a poor survival rate, which is typically less than 6 months. A radio-neuroendocrine approach utilizing radiotherapy with melatonin supplementation (20 mg) in brain glioblastoma patients showed that the likelihood of survival at one year was significantly higher in those who received melatonin with radiotherapy versus radiotherapy alone (Lissoni et al. 1996). Moreover, patients had reduced radiation and steroid-related toxicities when melatonin was consumed nightly (Lissoni et al. 1996).

It recently has been suggested that melatonin may diminish the risk of hypoperfusion-induced cerebral ischemia (Delagrange et al. 2003). Therefore, melatonin supplementation may prolong the survival of patients undergoing radiotherapy (Blask et al. 2002).

Melatonin also may provide relief from the detrimental side effects of radiation treatment (Jatoi et al. 2002) (including toxicity to the heart, kidneys, and nerves—cardiotoxicity, nephrotoxicity, and neurotoxicity, respectively), immune suppression, pain, anemia, fatigue, and sleep disturbances (Lissoni et al. 1996). Supplementing cancer patients with melatonin may have some benefit for successful radiotherapy (Sener et al. 2003).

It is well established that solid tumors contain hypoxic areas and that oxygen levels in such areas will cause tumors to be resistant to ionizing radiation (Vaupel et al. 2001). Inoperable cervical cancer is normally treated with radiotherapy. Several in vivo and in vitro studies suggest an improvement of radiosensitivity by adding retinoids and alpha-interferon in squamous cell cervical cancer treatment (Dunst et al. 1999).

In a 2-week pretreatment study with retinoic acid plus interferon-alpha-2a prior to definitive radiation therapy in cervical cancer patients, complete clinical remission of the local tumor in 19 of 22 patients after radiotherapy and additional retinoic acid plus interferon-alpha-2a treatment was reported. In primarily hypoxic tumors, four out of five achieved complete remission (Dunst et al. 1998).

During radiotherapy of cervical cancer patients with well-oxygenated tumors, 87% (20 of 23) achieved a clinically complete response using radiotherapy plus 13-cis-retinoic acid/interferon. In patients with primarily hypoxic tumors, all six patients whose primarily hypoxic tumors showed an increase of the median oxygen levels achieved a complete remission. In contrast, only four of seven patients with low pretreatment and persisting low median oxygen achieved a complete remission. Evident changes occur in the oxygenation of cervical cancers during a course of fractionated radiotherapy. In primarily hypoxic tumors, a significant increase of the median oxygen was found. An additional treatment with 13-cis-retinoic acid and interferon further improve the oxygenation status (Dunst et al. 1999).

If you (or a member of your family) are undergoing radiotherapy, this new information should be brought to your physician's attention.

In animal studies, when ginseng was administered along with radiation therapies, a far greater percentage of the animals survived in the ginseng-supplemented group, compared with the group administered radiation without ginseng (Yonezawa et al. 1981; Rhee et al. 1991; Kim et al. 1993, 1996). Cancer patients should consider taking 2-4 capsules daily of Sports Ginseng by Nature's Herbs, which combines Korean and Siberian ginseng.

Radiation-induced pneumonitis can be treated with antioxidants; however, the exact cause of pneumonitis is not known. Pneumonitis is thought to occur as a result of excessive generation of free radicals in healthy tissue following radiotherapy.

In vitro studies have shown that large doses of radiation can cause membrane lipid peroxidation and the oxidation of protein groups. Radiation-induced pneumonitis was studied using 25 patients who underwent radiotherapy for inoperable nonsmall cell lung cancer. Blood samples were taken over a 3-month period, and it was found that 40% (10 of 25) of the patients developed pneumonitis and that these patients had significantly higher levels of free radicals and iron in their blood. Iron is a catalyst for free-radical reactions (Jack et al. 1996).

A serious side effect from cancer radiation therapy is fibrosis to healthy tissues. Fibrosis is an inflammatory condition that causes progressive scarring to healthy tissue that can lead to debility or death. Antioxidants not only have been shown to prevent fibrosis, but also to reverse it. It would appear that patients undergoing radiation procedures might derive therapeutic and protective benefits if they consumed the proper antioxidants before, during, and after therapy. The downside, critics argue, is that long-term survival studies of radiation patients supplementing with high doses of antioxidants are lacking.

Radiation fibrosis is an extreme complication, without effective treatment, after radiation therapy. Surgical removal and healing of a radiation-induced fibrosis is rarely successful.

One published case involved a 58-year-old woman who developed a radiation fibrosis in the irradiated area of a squamous cell carcinoma. Following the surgery, the woman was treated with a combination of pentoxifylline tablets (400 mcg 3 times daily) and vitamin E (one 400-mg capsule each day). The woman tolerated the treatment well and a noted improvement in the condition of the affected skin was seen, beginning at 4 months. A decrease in skin thickness could be demonstrated from the sixth month on, with the patient experiencing no side effects from this protocol. The data indicate a therapeutic effect on radiation-induced fibrosis by the synergistic administration of pentoxifylline and vitamin E. Pentoxifylline is a prescription drug that inhibits abnormal platelet aggregation and may allow more blood flow to the irradiated area (Gottlober et al. 1996).

Another study reported a "striking regression of radiation-induced fibrosis by a combination of pentoxifylline and tocopherol." Researchers reported a 50% regression of superficial radiation-induced fibrosis after a 6-month administration of pentoxifylline and tocopherol (vitamin E) in half of the patients studied (Delanian 1998).
The study also reported on a 67-year-old woman with a bulky radiation-induced fibrosis who, 10 years previously, had received radiochemotherapy for a small cell thyroid carcinoma with severe acute radiation side effects. She had palpable cervicosternal fibrosis measuring ~108 cm, with local inflammatory signs and functional consequences (cough, restricted cervical movement, dyspnea, and bronchitis). A CT scan revealed deep radiation-induced fibrosis extending from the vocal cords to the carina, with laryngotracheal compression, but without cancer recurrence. The patient received pentoxifylline (800 mg a day) and vitamin E (1000 IU a day), orally administered daily for 18 months. The patient exhibited clinical regression and functional improvement at 6 months and complete response with no measurable fibrosis at 18 months (Delanian 1998).

The combination of pentoxifylline and vitamin E seems to promote a significant anti-fibrotic effect by reversing deep radiation-induced fibrosis (Lefaix et al. 1999).

Individuals receiving treatment for cervical cancer, prostate cancer, or colorectal cancer may find significant relief from the effects of radiation-induced proctopathy by taking oral vitamin A. Radiation-induced anal ulcers characterized by diarrhea, urgency, rectal pain, rectal bleeding, and fecal incontinence may occur 6 months or more after irradiation of prostate and pelvic irradiation. In a double-blind placebo-controlled trial, Levitsky et al. (2003) successfully treated both male and female patients having radiation-induced anal ulcers with oral vitamin A. The trial group consisted of 14 males and 2 females with a median age of 71. Of the enrolled patients, 13 had been treated for prostate cancer, 2 had been treated for cervical cancer, and 1 had been treated for rectal cancer. Eight patients were randomized for vitamin A (8000 IU twice daily) and 8 patients were randomized for placebo.

After 3 months, 7 of 8 patients (88%) had a significant reduction in symptom parameters based on Fisher's Exact Test versus 2 of 8 patients (25%) who responded to placebo. Five nonresponders to placebo were then given the same therapeutic dose of vitamin A, and responded favorably to treatment. The researchers concluded that the vitamin A-treated test subjects showed a significant reduction in symptoms of proctopathy as compared to placebo. Improved rectal function and decreased bleeding were attributed to the wound healing and repair properties of vitamin A.

The risk of pneumonitis may be reduced by antioxidant therapy. There are several specific nutrients that can be taken to improve the immune system after radiotherapy. General supplementation with antioxidants, such as vitamins A, C, and E, and with the sulfur amino acids cysteine and glutathione is known to reduce free-radical damage caused by radiation therapy. While protection of healthy tissue would best be accomplished if these nutrients were administered prior to radiation therapy, some scientists are concerned that these nutrients might help protect the tumor cells against the radiation-generated free radicals needed to kill all of the cancer cells.

Other scientists point to studies and case histories indicating a neutral or beneficial effect when antioxidants are consumed prior to radiation treatment. A radiation oncologist who has prescribed high dose antioxidants to cancer patients prior to radiation therapy for over 20 years states that the potent amount of radiation delivered to the tumor during therapy would overwhelm the free-radical-quenching effects of orally ingested antioxidants (Smith 2002). According to this physician, antioxidants protect against many of the side effects of radiation therapy such as immune suppression and peripheral tissue damage.

In addition, improved survival in cancer patients has repeatedly been shown to be associated with superior performance level and with improved self-perceived overall quality of life. Many elderly patients experience prompt improvement in performance level and prompt improvement in self-perceived quality of life when antioxidants such as vitamin C (1 gram 3 times daily), vitamin E (400 IU 3 times daily), and selenium (50 mcg 3 times daily) are added as food supplements.

As noted earlier, other experts are concerned that any type of antioxidant consumed before, during, or within 3 weeks after radiation therapy is concluded could protect the cancer cells against the radiation-induced, free radical activity that is needed to kill cancer cells.

Yet a 2002 study on this subject showed that tocopheryl succinate (dry powder vitamin E) enhanced radiation damage to ovarian and cervical cancer cells, but protected healthy cells. This study showed that both cancer and normal cells absorbed a similar amount of tocopheryl succinate, but only the cancer cells were sensitized to the radiation by this form of vitamin E. The use of alpha- tocopheryl succinate during radiation therapy may improve the efficacy of radiation therapy by enhancing tumor response and decreasing some of the toxicities on normal cells (Kumar et al. 2002).

An investigative study conducted by the Department of Radiation Oncology, Henry Ford Hospital in Detroit, MI, and the Department of Radiology, University of Colorado Health Science in Denver, CO, between March 1998 and December 2000, explored nutritional and high dose antioxidant interventions during radiation therapy (RT) for breast cancer. The researchers examined 48 randomized patients with Stage I-III breast cancer, 26 of whom received high dose antioxidant vitamins and followed a 10% low fat diet during their radiation treatment. Another 22 patients received only radiation treatment. Of the 48 patients, all were followed for a minimum of 14 months after radiation and evaluated with regard for local recurrence, skin reaction, vitamin levels, quality of life, and cholesterol levels pre-RT, during RT, and post-RT (Anon. 2002).

The researchers found that the addition of high dose antioxidant vitamins during radiation therapy for breast cancer had no increased risk of local recurrence or new cancer 1 year after treatment. However, in patients receiving no treatment other then radiation, one developed a new cancer in the opposite breast and another developed LCIS (lobular carcinoma in situ, defined as the growth and accumulation of large numbers of abnormal cells within the lobules of the breast tissue) in the opposite breast. No other statistically significant differences were observed. However, there were significant changes in the blood cholesterol values from pretreatment to post-treatment in the group receiving antioxidants and diet modification with significant increases in HDL (good) cholesterol and reductions in LDL (bad) cholesterol blood levels. The researchers concluded that further randomized studies should be conducted to determine the potential long-term benefits of high dose antioxidant vitamins and diet modification in early stage cancer.

Antioxidant vitamins could be an important adjuvant to standard treatment of human cancers (Prasad et al.1999; Prasad 2003).

The debate over whether antioxidants are beneficial before, during, and after radiation therapy continues. However, research is mounting that shows quality of life and long-term survival may be improved by combining high dose antioxidant therapy with traditional cancer treatments (Prasad 2003). Research also indicates that antioxidant therapy that is continued post-treatment may exert anticancer benefits.

One of the unpublicized side effects of radiotherapy is male impotency, especially in those patients being treated for prostrate cancer. A high percentage of men experience impotency after radiotherapy with little hope for recovery (Turner et al. 1999). However, treatment of erectile dysfunction with the drug Viagra after radiation therapy for prostate cancer was reported a success (Incrocci et al. 2003).

To determine the response to Viagra in patients with erectile dysfunction after radiation therapy for localized prostate cancer, 21 patients presenting with erectile dysfunction after radiation treatment for clinical T1-2 prostate cancer were studied: Two patients had undergone iodine-125 seed implantation; the remaining 19 had undergone conventional external beam irradiation.

All 21 patients were considered to have erectile dysfunction as assessed by the International Index of Erectile Function and were prescribed sildenafil (Viagra) at a dosage of 50 mg, with a titration to 100 mg if needed: 71% of patients had a positive response, with a corresponding spousal satisfaction rate of 71%. No patient discontinued the drug because of side effects (Kedia et al. 1999).

If you are experiencing impotency, consider consulting your physician and requesting that he or she prescribe 50-100 mg of Viagra daily to correct this sometimes overlooked adverse side effect of radiotherapy. Viagra is not without side effects. It may be causing more heart attacks than have been reported. If you have any kind of coronary artery occlusion, you may want to avoid Viagra, even if you are not taking nitrate drugs.

Shark liver oil containing standardized alkylglycerols can prevent immune impairment and irradiation injury to healthy tissues (Brohult et al. 1977). Shark liver oil can also help boost blood cell counts. Cancer patients should considersix 200-mg standardized shark liver oil capsules a day for 30 days. Shark liver oil can cause an overproduction of blood platelets, so high doses of shark liver oil should not be taken for more than 30 days.

The following therapies may enhance the cancer cell-killing effects of radiation therapy:

Arginine: Consuming 20-30 grams of arginine 30-60 minutes prior to each radiation session could dramatically improve the number of cancer cells killed. This is because cancer cells thrive in a low oxygen environment. Arginine enhances blood flow to tumors, thus enabling the radiation to generate more cancer cell-killing free radicals. Some people find it difficult to consume 20-30 grams of arginine orally. As an alternative, a physician could administer the arginine via an IV infusion 30 minutes before each radiation session. Arginine is available to doctors in IV dosing packs for the purpose of testing pituitary growth hormone response. Conventional doctors, however, are reluctant to try innovative approaches. Patients seeking to use high dose arginine prior to each radiation session have the following options:
- Swallowing 23-33 arginine (900-mg) capsules.
- Mixing 2.5-3.5 tablespoons of unpleasant-tasting arginine powder in water and drinking the mixture.
- Taking 4-6 tablespoons of an arginine-based drink called sugar-free PowerMaker II. This makes normally unpalatable arginine taste acceptable.
- Finding a physician in your area who will have his or her nurse administer the 20-30 grams of arginine by IV therapy prior to each radiation session. To find an innovative physician who might accommodate this IV arginine request, contact us.
To further saturate the tumor with oxygen, some patients breathe 95% oxygen during the radiation therapy (Kaanders et al. 2002).
Check the oxygen-carrying capacity of blood by testing the blood for red blood cell count, hematocrit, and hemoglobin. It is critical that these blood oxygen indictors be in the upper one-third level of normal. This can be accomplished with the drug Procrit, which must be prescribed by your oncologist. It may take as long as 6 weeks for Procrit to achieve maximum effect. For Procrit to be effective, there must be adequate iron present. Supplementing with 30 mg a day of iron protein succinylate, sold under the brand name Iron Protein Plus, will provide additional iron to help Procrit work effectively.

Certain nutrients may help prevent cancer cells from developing resistance to radiation therapy. Since these nutrients also function as antioxidants (meaning they suppress free-radical activity), you may decide to use them 3 weeks after radiation therapy rather than during radiation therapy. These nutrients are

Curcumin, 900 mg with 5 mg piperine (an alkaloid from Piper nigrum), 3 capsules, 2-4 times a day. (Super Curcumin with Bioperine is a formulated product that contains this suggesteddosage.)
Warning: Use caution when combining curcumin with drugs. Take 2 hours away from all medications. Do not take with the chemotherapy drugs irinotecan, Camptosar, or CPT-11. Watch for NSAID-like side effects such as gastric ulceration because curcumin is a COX-II inhibitor. Do not take curcumin if there is a biliary tract obstruction. Note that curcumin is a potent antioxidant.
Ultra Soy Extract (40% isoflavones), five 700-mg capsules four times daily.
Green tea extract (95% polyphenols), five 350-mg capsules with each meal (3 meals a day). These are available in decaffeinated form for those who are sensitive to caffeine or who want to take the less stimulating decaffeinated green tea extract capsules in their evening dose.
Alpha-interferon and Accutane: Consult your physician. A study reports on dosages of 6 million units of alpha-interferon and 1 mg per kilogram of body weight of the retinoid drug Accutane daily for 12 days prior to radiation therapy. (During the radiation therapy sessions, the dosages were reduced to 3 million units of alpha-interferon 3 times a week and 0.5 mg per kilogram of body weight of Accutane until the maximum dosage of radiation was achieved).
Vitamin A, 25,000 IU a day. (Refer to Appendix A: Avoiding Vitamin A Toxicity .)
Ginseng, two to four 200-mg standard dosage Sports Ginseng capsules daily.

The following drugs and supplements may reduce side effects and damage caused by radiation therapy:

Pentoxifylline and vitamin E (tocopheryl succinate), one 400-mg pentoxifylline tablet taken twice daily with two 400-IU capsules of vitamin E and 1 capsule of Gamma E Tocopherol.
Melatonin, 20 mg nightly. Dose may be reduced to 3-10 mg each night after 30 days if morning drowsiness occurs.
Taurine, 2000 mg daily.
Shark liver oil, six 200-mg standardized shark liver oil capsules a day for 30 days prior to radiation therapy.
Caution: Shark liver oil can cause an overproduction of blood platelets, so high doses of shark liver oil should not be taken for more than 30 days. Platelet levels should be closely monitored (at least every month).
Vitamin C, 4000-12,000 mg a day, in divided doses.
Se-methylselenocysteine (SeMSC), 200-400 mcg daily.
N-acetyl-cysteine (NAC), 600 mg 1 time each day.
Whey protein concentrate isolate, 10-20 grams three times a day, at least 10 days before beginning therapy and during therapy and then continuing with the whey protein for at least 30 days after completion of the therapy.

Vitamin A, Vitamin C, Vitamin D; Gamma E Tocopherol/Tocotrienols; shark liver oil capsules; whey protein concentrate; taurine; tocopheryl succinate; ginseng; Ultra Soy; Super Curcumin; Super Green Tea Extract; Se-methylselenocysteine (SeMSC), arginine capsules and powder; N-acetyl-cysteine; PowerMaker II; melatonin; and Iron Protein Plus can be obtained by calling contacting us . Pentoxifylline and Procrit are prescription medications.