Antioxidants and natural compounds can improve the effectiveness of radiotherapy and chemotherapy. Fact.

Firstly, The myth of the Clinical Trial

Increasingly, the orthodox medical world is demanding that all cancer treatments must have scientific research evidence to support their use. The ‘gold standard’, often quoted, is largely limited to chemotherapy drugs and is called the ‘Clinical Trial’.

At icon we agree with this need. 

accurate measurements of the negative side effects of a drug are every         bit as important as measuring the benefits

However, only about 15 per cent of all drugs on the market in the USA have been through a clinical trial, about 80 per cent of drugs are cheaper ´generic´ copies and all too often the patient is given, not one drug, but several, the combination of which has never been near a Clinical Trial (Double blind, placebo whatever, or otherwise).

Worse, the placebo effect is seeing the ´benchmark, control´ sugar pill produce side effects and even cure some patients. 

Worse still, whilst PR firms of Pharma companies rush to tell the benefits of their new wonder drugs, the rigour of exactly how many people benefit from the drug often falls woefully short when the issue of how many people succumb to side effects is considered. These are most usually ‘touched upon’ rather than provided as accurate percentages in the same way the benefits are measured. We have covered (in a previous issue – Vol 2 ; 2006) the concerns expressed by experts in the Lancet Oncology magazine of the negative effects of, say, monoclonal antibodies. As we have expressed before in icon, accurate quantified measurements over a sensible period of time of the negative side effects of a drug are every bit as important as measuring the benefits.

Finally, in some cases, euphoria on the positive findings is seeing some ´wonder´ drugs pulled out of Clinical Trials before they have even completed their allotted time span. How rigorous is that?

You may be saying, ´What´s all this got to do with whether I should take antioxidants with Chemotherapy and radiotherapy?´. The answer is everything. Because often, the very people who tell you that All drugs have been through extensive Clinical Trials´ are the very same people who criticise antioxidants and vitamins on the grounds that they haven´t. This rigour is lacking with supplements. It is mythology; pure mythology. 

In Cancer Watch we covered research, again from the Lancet, on how ‘vested interest’ research is reducing the credibility of Doctors and Specialists alike amongst the general public.

Bashing antioxidants

Next, all too often, ´informed research papers´ are presented by experts who turn out to be  ‘interested parties’ with some vested interests or more than a little bias.

In 2004 and 2005 two ‘megastudies’ criticising anti-oxidants were covered in icon magazine. In response to a concern expressed by Professor Tony Howell, one of our charity patrons, we analysed the data to find, for example in one case with vitamin E, that far from being a ‘megastudy’, the scientists had only ´chosen´ 14 studies out of over 800 available, (far less than we considered for our own report on vitamin E) and far from looking at the natural vitamin in its 4 tocopherol forms or its 4 tocotrienol forms, the only research taken by the scientists was for the synthetic vitamin E in solely the alpha-tocopherol form. (Which, for example, has virtually no proven benefit with breast cancer, unlike the tocotrienol forms; and worse, recent Japanese research says it can knock out the effects of two of the tocotrienols!)

From this megastudy they managed to conclude that ‘vitamin E could actually increase your risks of dying by 10-30%’. Poor research at best (Cancer Research UK agreed with us), but possibly no co-incidence that it was published shortly before the decisions in the EU were to be made on whether vitamins should be treated as drugs and which would be permitted for sale in the shops.

For the record, our view is that some high street antioxidants are often synthetic copies of the real thing, and with less available variant forms than occur naturally. For example you take antioxidant vitamin E to find it is synthetic and contains only one of the 8 forms nature provides; beta-carotene can be synthetic and contain only one of the two naturally occuring forms. Synthetic vitamin C, contains no co-factors or bioflavenoids. Research on a side by side test against fresh orange juice, should the synthetic vitamin provide no antioxidant power whatso ever during a 24 hour period.

I liken them to Thai copies of Gucci Handbags. Are you surprised when the handle falls off?

So, should you take these antioxidants with your chemo and radiotherapy? Answer? You are probably just wasting your money.

Sorry, but Doctors have no idea

Sadly, Doctors have little understanding of nutrition, less on natural compounds and have little time to read anything. In icon we reported on the senior Australian Government Medical Advisor who has set up a website for doctors to tell them about drugs and pharmaceutical clinical trials, listing all benefits and side effects, because he was so concerned that ‘doctors only get that information from PR releases and media coverage, both of which are provided by the pharmaceutical companies themselves and may be biased’.

Doctors rarely ever study nutrition at Medical School and do not pass exams in it.

Antioxidants actually help chemo and radio work!

As an example, one of the most commonly asked questions by people ringing our offices is, ‘Should I be taking my anti-oxidants when I have chemo or radiotherapy?’

Our answer is a categoric, ‘YES’. By why restrict yourself to antioxidants - THERE ARE LOADS OF NATURAL COMPOUNDS THAT CAN HELP YOU!!!!

Elsewhere on this web site we have covered the ‘tome’ by John Boik, one of the senior staff at the prestigious MD Anderson Cancer Centre in Houston, Texas. This book is over an inch thick, published in 2001 and called ‘Natural Compounds in cancer therapy’. It contains over 4000 references to scientific papers and basically concludes that, far from in some way interfering with the biochemical process involved in chemo or radiotherapy, taking anti-oxidants actually improves the success rates of both. Support for this stance came in 2005 – again covered in icon Cancer Watch, when UCLA produced the conclusion that healthy cells are self regulators and will pick up the maximum concentrations of anti-oxidants available in order to maximize their biochemical processes. However cancer cells have lost most of this regulatory ability and will overload on anti-oxidants. Their view is that this will help the chemo or radio ‘kill them off’.

a number of oncologists adamantly tell their patients that they do not want them taking anti-oxidants during their chemo or radiotherapy

The problem for us, and especially for the cancer patients who call us, is that a number of oncologists adamantly tell their patients that they do not want them taking anti-oxidants during their chemo or radiotherapy as this will somehow weaken the effect. Patients are thus ‘scared’ into dropping their supplementation programmes. Our problem is compounded because we are very open minded on this issue still, but frequent requests to be sent the ‘hard scientific research evidence’ supporting the oncologist’s concern have come to nothing. We would be happy to print it. But does any actually exist, or is the concern pure subjective opinion and mythology?

Natural Compounds increase Survival Times. Fact.

On the other hand, in Cancer Watch we have covered several research studies where vitamin E improves the success of a drug; or astragalus improves the success of radiotherapy; or green tea improves the success of chemo and radio, as do medicinal mushrooms. And all increase survival times. This is important, for goodness sake! Doctors should know this and be encouraging their patients to take these natural compounds. 

The detractors persist

In September 2005 a paper was actually published in the USA in ´A Cancer Journal for Clinicians´ (Gabriella D’Andrea MD). More of an article than a genuine scientific paper, it warned against using anti-oxidants with chemo and radiotherapy. However by chance, or oversight, it missed all the papers supporting anti-oxidants, used only clinical laboratory research rather than human or epidemology studies, and omitted the fact that in certain cases (e.g. the use of amifostine) some specific and synthetic anti-oxidants are approved by the FDA and recommended for use with chemotherapy and are known to have enhancing benefits in, say, oral and lung cancers and child leukemia.

 specific and synthetic anti-oxidants are approved by the FDA and recommended for use with chemotherapy

icon, for example, carried clinical research in 2004 that vitamin E supplementation could produce the same positive effects from Tamoxifen, at a 25  per cent lowered drug dosage. Great for the patient – but not so great for the profitability of the pharmaceutical company concerned. We doubt any oncologist has even noticed the research. Further research has shown that the use of natural compound indole3carbinol also means you need to use less Tamoxifen. 

The D’Andrea article did, however, re-open the debate about taking anti-oxidants with chemotherapy and radiotherapy.

The whole matter has recently been highlighted by Ralph W. Moss PhD, the famous US cancer researcher. In a paper ‘Should patients undergoing Chemotherapy and Radiotherapy be prescribed antioxidants? (Integrative Cancer Therapies Vol 5, 1; 63-82. http://ict.sagepub.com/cgi/reprint/5/1/63. Also on PubMed) Moss expertly takes the reader through the myriad of research, including clinical trials, stating clearly that the D’Andrea paper was incomplete and that there is far more information available than either she included or is widely acknowledged. His conclusion is that a ‘blanket rejection of the concurrent use of anti-oxidants with chemotherapy is not justified by the preponderance of evidence’. For the more scientifically biased amongst our readers we have listed below some of the main scientific references on this subject.

If taking anti-oxidants is of such a concern, why do  many of the same oncologists tell the patient to eat plenty of fresh fruit and vegetables instead?

Moss raises another important point - one we have repeatedly made. If taking anti-oxidants is of such a concern, why do many of the same oncologists tell the patient to eat plenty of fresh fruit and vegetables instead? Is it because they believe fresh fruit and vegetables are devoid of anti-oxidants these days and thus can’t interfere with their chemotherapy? Or is it because they are fearful of the synthetically produced ones? (Just as we are – you’ll note in icon we continually tell you to take the natural forms). Perhaps it is neither of these. Perhaps they are just not aware of the enormous amount of research in the US alone.  However, the answer may lie in an article from the early days of icon, when Dr. Graham Henderson wrote a piece for us telling our readers just why UK Doctors were so negative towards complementary therapies. To summarise: UK Doctors want to be the fount of all knowledge for their patients, and many have neither studied formally, nor had the time to study since leaving medical school, these complementary therapies and especially nutrition. (Only recently a newly qualified doctor was in our offices openly stating that (apart from a morning on combating heart disease) she had not spent one day formally studying nutrition in her whole seven years training!) As Dr. Henderson concluded, most UK Doctors are outside their both knowledge and comfort zones.

Nothing brings this home more than reading Moss’ conclusions, one of which is that ‘Patients would be well advised to seek the opinion of physicians who are adequately trained and experienced in the intersection of 2 complex fields, that is, chemotherapy and nutritional oncology’.

If all UK NHS oncologists who qualify e-mail us on enquiries@canceractive.com with their name, phone number and qualifications we will happily publish a list in the magazine and on our web site. This debate will not be settled until we have more experts who are fully qualified in both oncology and nutritional therapy.

Meanwhile, a similar view on the benefits and the increasingly vacuous criticism of natural compounds as beneficial adjuncts to chemo and radiotherapy can be found in the article on Herbs by the expert Alan Hopking in icon Issue 3 2006.

For the record, we continue to recommend that all patients having chemo and radiotherapy supplement using natural supplements (like Chlorella, garlic, astragalus, Aloe Vera, medicinal mushrooms, green tea, selenium, natural vitamin E etc) as we increasingly find positive research-based evidence.  (For example:  Prasad K. N:  Int. Cancer Therapies 2004, 3:3, 310-323.  Multiple dietary antioxidant therapies enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. But we especially recommend that patients load up on the foods that can provide them with the biggest range of cancer fighting agents possible.

          At last, the definitive, research-based book on how to build a diet to help beat cancer. Click here to read about it.

References:

For those of you who want to check the scientific references used, we have selected a mere 75 from those recorded by Ralph Moss

************************************************************************

Some detailed references:

• D’Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin. 2005;55:319-321
• Parker-Pope T. Cancer and vitamins: patients urged to avoid supplements during treatment. Wall Street Journal. September 20, 2005:D1.
• Cohen MH. Complementary and Alternative Medicine: Legal Boundaries and Regulatory Perspectives. Baltimore, Md: Johns Hopkins University Press; 1997.
• Moss RW. Antioxidants Against Cancer. Brooklyn, NY: Equinox Press; 2000.
• Prasad KN. Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. Integr Cancer Ther. 2004;3:310-322.
• Conklin KA. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer. 2000;37:1-18.
• Conklin K. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther. 2004;3:294-300.
• Jiang Q, Wong J, Fyrst H, Saba JD, Ames BN. Gammatocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. Proc Natl Acad Sci USA. 2004;101:17825-17830.
• Ferrari CK. Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging. Biogerontology. 2004;5:275-289.
• Drisko JA, Chapman J, Hunter VJ. The use of antioxidant therapies during chemotherapy. Gynecol Oncol. 2003;88:434-439.[CrossRef[Medline [Order article via Infotrieve
• Chen Q, Espy MG, Krishna MC, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A. 2005;102:13604-13609.[Abstract/Free Full Text
• Paiva SAR, Russell RM. Beta-carotene and other carotenoids as antioxidants. J Am Coll Nutr. 1999;18:426-433.[Abstract/Free Full Text
• Young AJ, Lowe GM. Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys. 2001;385:20-27.[CrossRef[Medline [Order article via Infotrieve
• Bairati I, Meyer F, Gelinas M, et al. Randomized trial of anti-oxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol. 2005;23:5805-5813.[Abstract/Free Full Text
• Bairati I, Meyer F, Gelinas M, et al. A randomized trial of anti-oxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-488.[Abstract/Free Full Text
• Camphausen K, Citrin D, Krishna MC, Mitchell JB. Implications for tumor control during protection of normal tissues with antioxidants. J Clin Oncol. 2005;23:5455-5457.[Free Full Text
• Block K. Antioxidants in the news. Integr Cancer Ther. 2005;4:271-273.[Free Full Text
• Creagan ET, Moertel CG, O’Fallon JR, et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer: a controlled trial. N Engl J Med. 1979;301:687-690.
• Moertel CG, Fleming TR, Creagan ET, Rubin J, O’Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy: a randomized double-blind comparison. N Engl J Med. 1985;312:137-141.
• Padayatty SJ, Sun H, Wang Y, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140:533-537.[Abstract/Free Full Text
• Memorial Sloan-Kettering Cancer Center. Cancer tumors shown to consume large amounts of vitamin C [press release. September 15, 2000. Available at: www.mskcc.com.
• Newbold HL. Vitamin C Against Cancer. New York, NY: Stein & Day; 1979.
• Gonzalez MJ, Miranda-Massari JR, Mora EM, et al. Orthomolecular oncology review: ascorbic acid and cancer 25 years later. Integr Cancer Ther. 2005;4:32-44.[Abstract/Free Full Text
• Jaakkola K, Lahteenmaki P, Laakso J, Harju E, Tykka H, Mahlberg K. Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res. 1992;12:599-606.[Medline [Order article via Infotrieve
• Lesperance ML, Olivotto IA, Forde N, et al. Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study. Breast Cancer Res Treat. 2002;76:137-143.[CrossRef[Medline [Order article via Infotrieve 
• Alam N, Shepherd FA, Winton T, et al. Compliance with postoperative adjuvant chemotherapy in non-small cell lung cancer: an analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer. 2005;47:385-394.[CrossRef[Medline [Order article via Infotrieve
• Hoffer A. Comments on "Mega-Dose Vitamins and Minerals in the Treatment of Nonmetastatic Breast Cancer: An Historical Cohort Study." Integr Cancer Ther. 2003;2:155-157.[Free Full Text
• Conklin K. Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integr Cancer Ther. 2005;4:110-130.[Abstract/Free Full Text
• Bertazzoli C, Sala L, Ballerini L, Watanabe T, Folkers K. Effect of adriamycin on the activity of the succinate dehydrogenasecoenzyme Q10 reductase of the rabbit myocardium. Res Commun Chem Pathol Pharmacol. 1976;15:797-800.[Medline [Order article via Infotrieve
• Cortes EP, Gupta M, Chou C, Amin VC, Folkers K. Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep. 1978;62:887-891.[Medline [Order article via Infotrieve
• Brash DE, Havre PA. New careers for antioxidants. Proc Natl Acad Sci U S A. 2002;99:13969-13971.[Free Full Text
• Shin DM, Khuri FR, Murphy B, et al. Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial. J Clin Oncol. 2001;19:3010-3017.[Abstract/Free Full Text
• Seixas-Silva JA Jr, Richards T, Khuri FR, et al. Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: long-term follow-up. Arch Otolaryngol Head Neck Surg. 2005;131:304-307.[Abstract/Free Full Text
• Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol. 2003;21:927-931.[Abstract/Free Full Text
• Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology. 2005;64:26-31.[Abstract/Free Full Text
• Delanian S, Porcher R, Balla-Mekias S, Lefaix JL. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol. 2003;21:2545-2550.[Abstract/Free Full Text
• Delanian S, Depondt J, Lefaix JL. Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck. 2005;27:114-123.[CrossRef[Medline [Order article via Infotrieve
• Pathak AK, Bhutani M, Guleria R, et al. Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer. J Am Coll Nutr. 2005;24:16-21.[Abstract/Free Full Text
• Kennedy M, Brunuinga K, Mutlu EA, Losurdo J, Choudhary S, Keshavarian A. Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E and C. Am J Gastroenterol. 2001;96:1080-1084.[CrossRef[Medline [Order article via Infotrieve
• Mahmoud F, Sarhill N, Mazurczak MA. The therapeutic application of melatonin in supportive care and palliative medicine. Am J Hosp Palliat Care. 2005;22:295-309.[Medline [Order article via Infotrieve
• Jang MH, Jung SB, Lee MH, et al. Melatonin attenuates amyloid beta 25-35-induced apoptosis in mouse microglial BV2 cells. Neurosci Lett. 2005;380:26-31.[CrossRef[Medline [Order article via Infotrieve
• Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res. 2003;35:12-15.[CrossRef[Medline [Order article via Infotrieve
• Cerea G, Vaghi M, Ardizzoia A, et al. Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations. Anticancer Res. 2003;23:1951-1954.[Medline [Order article via Infotrieve
• Lissoni P, Malugani F, Bukovec R, et al. Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients. Neuro Endocrinol Lett. 2003;24:83-85.[Medline [Order article via Infotrieve
• Lissoni P, Bucovec R, Bonfanti A, et al. Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia. J Pineal Res. 2001;30:123-126.[CrossRef[Medline [Order article via Infotrieve
• Rybak LP, Husain K, Morris C, Whitworth C, Somani S. Effect of protective agents against cisplatin ototoxicity. Am J Otol. 2000;21:513-520.[Medline [Order article via Infotrieve
• Miyajima A, Nakashima J, Tachibana M, Nakamura K, Hayakawa M, Murai M. N-acetylcysteine modifies cisdichlorodiammineplatinum-induced effects in bladder cancer cells. Jpn J Cancer Res. 1999;90:565-570.[Medline [Order article via Infotrieve
• Bohm S, Oriana S, Spatti G, et al. Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma. Oncology. 1999;57:115-120.[CrossRef[Medline [Order article via Infotrieve
• Smyth JF, Bowman A, Perren T, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann Oncol. 1997;8:569-573.[CrossRef[Medline [Order article via Infotrieve
• Cascinu S, Catalano V, Cordella L, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2002;20:3478-3483.[Abstract/Free Full Text
• National Cancer Institute. Overview of nutrition in cancer care. June 17, 2005. Available at: http://www.cancer.gov/cancerinfo/pdq/supportivecare/nutrition
• Ladner C, Ehninger G, Gey KF, Clemens MR. Effect of etoposide (VP16-213) on lipid peroxidation and antioxidant status in a high-dose radiochemotherapy regimen. Cancer Chemother Pharmacol. 1989;25:210-212.[CrossRef[Medline [Order article via Infotrieve
• Clemens MR, Ladner C, Ehninger G, et al. Plasma vitamin E and beta-carotene concentrations during radiochemotherapy preceding bone marrow transplantation. Am J Clin Nutr. 1990;51:216-219.[Abstract/Free Full Text
• Colasanto JM, Prasad P, Nash MA, Decker RH, Wilson LD. Nutritional support of patients undergoing radiation therapy for head and neck cancer. Oncology (Williston Park). 2005;19:371-379.[Medline [Order article via Infotrieve
• Lissoni P, Paolorossi F, Ardizzoia A, et al. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res. 1997;23:15-19.[Medline [Order article via Infotrieve
• Yu D, Duan Y, Bao Y, Wei C, An L. Isoflavonoids from Astragalus mongholicus protect PC12 cells from toxicity induced by L-glutamate. J Ethnopharmacol. 2005;98:89-94.[CrossRef[Medline [Order article via Infotrieve
• Taixiang W, Munro AJ, Guanjian L. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev. 2005:CD004540.
• Kennedy DD, Ladas EJ, Rheingold SR, Blumberg J, Kelly KM. Antioxidant status decreases in children with acute lymphoblastic leukemia during the first six months of chemotherapy treatment. Pediatr Blood Cancer. 2005;44:378-385.[CrossRef[Medline [Order article via Infotrieve
• Kennedy DD, Tucker KL, Ladas ED, Rheingold SR, Blumberg J, Kelly KM. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr. 2004;79:1029-1036.[Abstract/Free Full Text
• Yildirim I, Korkmaz A, Oter S, Ozcan A, Oztas E. Contribution of antioxidants to preventive effect of mesna in cyclophosphamide-induced hemorrhagic cystitis in rats. Cancer Chemother Pharmacol. 2004;54:469-473.[CrossRef[Medline [Order article via Infotrieve
• Ozcan A, Korkmaz A, Oter S, Coskun O. Contribution of flavonoid antioxidants to the preventive effect of mesna in cyclophosphamide-induced cystitis in rats. Arch Toxicol. 2005;79:461-465.[CrossRef[Medline [Order article via Infotrieve
• Food and Drug Administration. Zinecard (dexrazoxane for injection). NDA 20-212/S-008. Available at: http://www.fda.gov/medwatch/safety/2005/MAY_PI/Zinecard_PI.pdf.
• Food and Drug Administration, Center for Drug Evaluation and Research. FDA oncology tools approval summary for dexrazoxane for reducing the incidence and severity of cardiomyopathy, October 31, 2002. Available at: http://www.accessdata.fda.gov/scripts/cder/onctools/summary.cfm?ID=256.
• Hensley ML, Schuchter, LM, Lindley, C, et al. American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol. 1999;17:3333-3355.[Abstract/Free Full Text
• Marzatico F, Porta C, Moroni M, et al. In vitro antioxidant properties of amifostine (WR-2721, Ethyol). Cancer Chemother Pharmacol. 2000;45:172-176.[CrossRef[Medline [Order article via Infotrieve
• Kemp G, Rose P, Lurain J, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. JClinOncol. 1996;14:2101-2112.[Abstract/Free Full Text
• Food and Drug Administration, Oncology Division Advisory Committee. Fulfillment of the accelerated approval requirements for the non-small cell lung cancer indication: ethyol (Amifostine) reduces the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced non-small cell lung cancer. Available at: http://www.fda.gov/ohrms/dockets/ac/03/briefing/3936B1_05_MedImmune-Eythol.htm.
• Schiller JH. High-dose cisplatin and vinblastine plus amifostine for metastatic non-small cell lung cancer. Semin Oncol. 1996;23:78-82.[Medline [Order article via Infotrieve
• Brizel DM, Wasserman TH, Henke M, et al. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol. 2000;18:3339-3345.[Abstract/Free Full Text
• Lipshultz SE, Rifai N, Dalton VM, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med. 2004;351:145-153.[Abstract/Free Full Text
• Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996;88:1550-1559.[CrossRef[Medline [Order article via Infotrieve
• Food and Drug Administration. Gefitinib (marketed as Iressa) information. 2005. Available at: http://www.fda.gov/cder/drug/infopage/gefitinib/default.htm.
• Mosman Communications, Inc. Industry news: AstraZeneca posts US$21B sales. Medical Observer. May 15, 2005. Available at: http://www.medobserver.com/mar2005/indnews.html.
• Lissoni P, Barni S, Brivio F, Rossini F, Fumagalli L, Tancini G. Treatment of cancer-related thrombocytopenia by low-dose subcutaneous interleukin-2 plus the pineal hormone melatonin: a biological phase II study. J Biol Regul Homeost Agents. 1995;9:52-54.[Medline [Order article via Infotrieve

Email: