אנטי-אוקסידנטים במינון גבוה לטיפול בסרטן

: J Am Coll Nutr. 2005 Feb;24(1):16-21. Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer. OBJECTIVE: In vitro AND animal studies suggest that antitumor effect of chemotherapeutic agents may be enhanced by antioxidants. Therefore, we initiated a clinical study to test the efficacy of high-dose multiple antioxidants (vitamins C, E AND beta carotene) as an adjunct to chemotherapy (paclitaxel AND carboplatin) in non-small-cell lung cancer. METHODS: 136 patients of stage IIIb AND stage IV NSCLC were randomized to receive chemotherapy (paclitaxel AND carboplatin) alone (chemotherapy arm, n = 72) OR chemotherapy in combination with ascorbic acid 6100 mg/day, dl-alpha-tocopherol (vitamin E) 1050 mg/day AND beta-carotene 60 mg/day (combination arm, n = 64). Survival were calculated by the Kaplan-Meier method AND compared using the log-rank test. RESULTS: An overall response rate (RR) of 33% was observed in chemotherapy arm with 24 patients showing a partial response (PR) AND none showing a complete response (CR). In combination arm the overall RR was 37% with 24 patients showing PR AND two showing CR. The median survival times in chemotherapy arm AND combination arm were nine AND 11 months respectively. The overall survival (OS) rates in chemotherapy arm AND combination arm at one year were 32.9% AND 39.1%, AND at two years, 11.1% AND 15.6% respectively. None of these differences were statistically significant (p = 0.20). Toxicity profiles were similar in both arms. CONCLUSIONS: These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy. Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and/or survival time in advanced lung cancer. ----------------------------------------------------------------------- P R Health Sci J. 2005 Dec;24(4):269-76. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. Case studies suggest that vitamin C, given intravenously at doses of 10-100 grams/day can improve patient well being AND in some cases, reduce tumor size. While ascorbate is generally considered safe, clinical data on high intravenous doses is limited. Twenty-four late stage terminal cancer patients were given continuous infusions of 150 to 710 mg/kg/day for up to eight weeks. Blood chemistry AND blood count profiles were obtained at roughly one-week intervals while patient health, adverse events AND tumor progression were monitored. The majority of patients were vitamin C deficient prior to treatment. Intravenous infusions increased plasma ascorbate concentrations to a mean of 1.1 mM. The most common adverse events reported were nausea, edema, AND dry mouth OR skin; AND these were generally minor. Two Grade 3 adverse events 'possibly related' to the agent were reported: one patient with a history of renal calculi developed a kidney stone after thirteen days of treatment AND another patient experienced hypokalemia after six weeks of treatment. White blood cell counts were stable while hemoglobin AND hematocrit levels dropped slightly during treatment, consistent with trends observed prior to therapy. Blood creatinine, BUN, glucose, AND uric acid concentrations decreased OR remained stable during therapy, suggesting that ascorbate infusions did not adversely affect renal function. One patient had stable disease AND continued the treatment for forty-eight weeks. These data suggest that intravenous vitamin C therapy for cancer is relatively safe, provided the patient does not have a history of kidney stone formation. ---------------------------------------------------------------------- CMAJ. 2006 Mar 28;174(7):937-42. Intravenously administered vitamin C as cancer therapy: three cases. Early clinical studies showed that high-dose vitamin C, given by intravenous AND oral routes, may improve symptoms AND prolong life in patients with terminal cancer. Double-blind placebo-controlled studies of oral vitamin C therapy showed no benefit. Recent evidence shows that oral administration of the maximum tolerated dose of vitamin C (18 g/d) produces peak plasma concentrations of only 220 micromol/L, whereas intravenous administration of the same dose produces plasma concentrations about 25-fold higher. Larger doses (50-100 g) given intravenously may result in plasma concentrations of about 14,000 micromol/L. At concentrations above 1000 micromol/L, vitamin C is toxic to some cancer cells but not to normal cells in vitro. We found 3 well-documented cases of advanced cancers, confirmed by histopathologic review, where patients had unexpectedly long survival times after receiving high-dose intravenous vitamin C therapy. We examined clinical details of each case in accordance with National Cancer Institute (NCI) Best Case Series guidelines. Tumour pathology was verified by pathologists at the NCI who were unaware of diagnosis OR treatment. In light of recent clinical pharmacokinetic findings AND in vitro evidence of anti-tumour mechanisms, these case reports indicate that the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed. ----------------------------------------------------------------- CMAJ • March 28, 2006; 174 (7). High-dose vitamin C therapy: Renewed hope OR false promise? Complementary AND alternative medicine is commonly used by patients with cancer. Anywhere from 22% to 69% of cancer patients may take herbal medicine, medicinal teas, vitamins AND minerals, AND use visualization techniques.1 There is often great pressure put on oncologists by their patients to support the use of AND even to prescribe alternative therapies for the treatment of cancer, in particular when no cure OR effective therapy exists. Although oncologists might dissuade their patients from pursuing therapies that are likely to be ineffective, in the face of desperate circumstances many patients insist on taking complementary AND alternative medicine concurrently with "standard" therapies. A critical concern of most oncologists is whether use of complementary AND alternative therapies can cause harm, especially when taken concurrently with a chemotherapy regimen that has a narrow therapeutic index. But should our concern move beyond adverse events? If a large proportion of patients are interested in alternative remedies that have biologically plausible therapeutic potential, it is the responsibility of conventional medicine to encourage the preclinical AND clinical research necessary to demonstrate OR refute the efficacy AND safety of these treatments, according to the scientific method AND rigorous standards set for conventional cancer therapies.2 The Office of Cancer Complementary AND Alternative Medicine (OCCAM) at the US National Cancer Institute was established in 1998 for this purpose. Not only does it warn people of the harmful effects of some alternative therapies, it also directs them toward available clinical trials of complementary AND alternative therapies for cancer AND provides peer review AND funding for research into these therapies (www.cancer.gov/cam/). OCCAM also provides guidelines to standardize the reporting of cases of effective therapies. This format was used by Padayatty AND associates in this issue (page 937) to report on 3 cases where advanced malignant disease was effectively treated with high doses of intravenous vitamin C therapy.3 The detailed AND transparent reporting of these cases, with pathologic review by the National Cancer Institute, raises, once again, the possibility that high-dose intravenous vitamin C therapy may be effective against some cancers. However, these are only 3 individual cases of very different types of cancer, AND in each case there is a possible alternative explanation for the positive outcome. One patient had remission of renal cell carcinoma after vitamin C therapy; however, spontaneous remission has been reported.4This possibility is correctly raised by Padayatty AND colleagues. Another patient, before embarking on vitamin C therapy, underwent a transurethral resection of a stage T2 transitional cell bladder carcinoma; this treatment alone can result in long-term remission.5 In the third case described, a patient with diffuse large B-cell lymphoma refused chemotherapy but received radiation therapy. Radiation was once the standard of care for diffuse large B-cell lymphoma AND can lead to long-term remission, at least in earlier-stage cases.6Furthermore, all 3 patients received other forms of complementary AND alternative medicine that practitioners of alternative medicine may argue are effective in treating these cancers. Finally, these case reports omit the number of patients who received high-dose intravenous vitamin C therapy with no effect. Because these cases were collected over many years from several institutions, this number may be quite large AND the overall response rate quite low. Despite the possible alternative explanations for the favourable outcomes of the 3 patients, Padayatty AND associates AND CMAJ should be commended for publishing detailed case reports so that critical appraisal is possible. Although previous carefully performed randomized trials of oral vitamin C therapy involving patients with advanced cancer failed to demonstrate any therapeutic benefit,7,8 there is recent evidence from laboratory experiments to support the possibility that high-dose intravenous treatment might be more effective. Chen AND associates report that vitamin C levels achievable in vivo only by intravenous infusion are selectively cytotoxic in vitro to various cancer cell lines but not to normal cells by a mechanism involving formation of hydrogen peroxide.9This is consistent with a growing literature that reactive oxygen species play an important role in the mechanism of action of proven cancer treatments AND that impaired oxidation-reduction balance in cancer cells might cause induced reactive oxygen species to selectively kill cancer cells.10–12 Indeed, additional mechanistic studies may help define tumour types more likely to respond to this AND other strategies that induce reactive oxygen species. There is, therefore, both ample interest AND evidence to support research of high-dose vitamin C administered intravenously as a treatment for cancer. At our institution, we have taken the next step of conducting a phase I trial to establish the safety AND dosage of high-dose intravenous vitamin C therapy for patients with advanced cancer; we are collecting preliminary efficacy, quality-of-life AND pharmacokinetic data. Numerous pitfalls remain, including defining the most biologically active dose, which tumour types might be most sensitive AND the potentially confounding role of additional concomitant complementary AND alternative medicine. Nevertheless, continued rigorous preclinical AND early phase clinical trials of high-dose intravenous vitamin C therapy will provide a scientifically sound basis from which to accept OR reject this approach AND thus