N-acetylcysteine as Cancer Treatment We were unable to locate research demonstrating N-acetylcysteine (NAC) as an anti-tumor agent. NAC is known to be safe in doses well above that used in most human trials. Diarrhea is the most commonly reported side effect of higher doses.125 N-acetylcysteine with Radiation The effect of NAC on radiotherapy was observed in 10 patients with non-small cell lung cancer. NAC was administered by IV (100 mg/kg over 30 minutes) before the first radiation session, followed by 30 mg/kg IV over the next seven hours. They then inhaled a nebulized solution containing 600 mg NAC 30 minutes prior to and after each subsequent radiation treatment. Patients receiving NAC had tissue reactions and tumor responses from radiotherapy judged to be similar to a control group. Average survival time was similar between patients receiving NAC treatment and those who underwent radiation only. The authors concluded the treatment outcome did not justify the expense.126 An in vitro experiment showed that NAC is not likely to block the tumor cell killing effect of radiation.127 Application of gauze soaked in 10-percent NAC solution to the skin 15 minutes before radiotherapy was tested in an unblinded trial. Topical NAC appeared to be associated with more rapid healing and less use of analgesics compared with those in the control group.128 N-acetylcysteine with Chemotherapy NAC has been employed with a number of chemotherapy agents as a means of reducing toxicity. It has gained such recognition in this regard that it is often used in clinical trials as an adjunct to the therapy being tested. Animal studies have shown NAC protects against hematuria resulting from cyclophosphamide therapy without reducing its tumoricidal effect.129-131 A phase I human trial found 6 g/day NAC completely protected against hematuria, which is a dose-limiting side effect of ifosfamide (an analogue of cyclophosphamide).132 Another human study found similar results.133 Human trials with dosages as high as 140 mg/kg NAC were unable to show any prevention of cardiomyopathy due to treatment with doxorubicin. One of these trials also noted that NAC treatment was not associated with a reduction of the anti-tumor action of doxorubicin,134,135 and a mouse study concurred. This study also noted prevention of cardiotoxicity, which as noted above, was not replicated in human studies.136 Another animal study raises the possibility of a reduction of the anti-neoplastic action of doxorubicin by NAC. NAC did, however, lead to a significant reduction in cardiac toxicity.137 As data on the subject of doxorubicin with NAC are currently conflicting, this combination might best be avoided at this time. It has been shown in two separate in vitro studies that NAC inhibits the cytotoxic activity of cisplatin.138,139 NAC may have a role, however, in the reversal of renal toxicity due to cisplatin.140 Other than use in salvage therapy, the combination of cisplatin and NAC should also probably be avoided at this time. Glutathione as Cancer Treatment Glutathione is a tri-peptide thiol (sulfhydryl-containing) compound which is the major intracellular antioxidant in the body. A human study suggests oral glutathione is poorly absorbed, with negligible plasma concentrations found after administration of a single 3 g oral dose.141 This conclusion is contradicted by a rat study which found dietary glutathione was absorbed in a dose-dependent manner, and remained elevated in the plasma for three hours after administration.142 Aerosol administration of glutathione is an effective means of delivery to the plasma143, as is intravenous administration.144 Glutathione is thought to be non-toxic to humans,144 although one study found a 5 g oral daily dose was associated with GI irritation and sulfur odor.145 A case report from Japan in 1984 raised the possibility that glutathione might be an effective treatment for hepatocellular carcinoma. A trial of six hepatocarcinoma patients on 5 g oral glutathione daily found regression or stagnation of tumor growth in three patients. One patient also had a reduction in alpha-fetoprotein (a tumor marker) from 496 to 5. Two patients of the six survived for one year. These patients were both women, raising the possibility of a sex-dependent effect.145 In a rat study, oral administration of glutathione caused regression of liver tumors, and increased survival of tumor-bearing animals.146 The usefulness of glutathione as an anti-tumor agent may be limited to the liver, kidney, and peripheral neurons, as these are the only tissues believed to have sufficient transport enzymes for cellular uptake.144 For further discussion of glutathione as an antioxidant, refer to the review article by Kidd.147 Glutathione with Radiation A randomized pilot trial with 45 participants investigated the radioprotective effect of glutathione. Patients were administered 1200 mg glutathione or saline placebo intravenously 15 minutes prior to pelvic radiotherapy. Patients receiving glutathione suffered less from post-therapy diarrhea (28%, compared to 52% of controls) and were more likely to complete the treatment cycle (71% to 52%). Although the sample size was too small to show significance, the authors concluded glutathione was unlikely to interfere with the effect of radiation on neoplasms.148 The argument was not based on patient outcome. Glutathione with Chemotherapy Increased cellular concentrations of glutathione have been associated with resistance to both anthracyclines and platinum agents.149 Given the suggestion of the inability of most cell types to take up exogenous glutathione,144 decreased chemotherapy efficacy due to glutathione administration may be limited to liver, kidney, and neurological tumors. The use of cisplatin and glutathione concurrently has been studied in several small human trials. One human trial found 3 g/m2 intravenous glutathione given 20 minutes prior to cisplatin (100 mg/m2) led to a significant reduction in nephrotoxicity in patients with ovarian cancer compared with those receiving cisplatin alone. There was a trend toward greater tumor response in the glutathione group--73 percent, compared to 62 percent in the control group.150 A similar trial using smaller doses of glutathione (2500 mg/m2) and cisplatin (50 - 75 mg/m2) did not find the reduction in nephrotoxicity reported above. However, the trend toward greater tumor response with glutathione treatment (72% response, compared to 52% in controls) was comparable.151 A double-blind trial studied the neuroprotective effect of intravenous glutathione (1500 mg/m2) during cisplatin treatment for gastric cancer. After nine weeks, no patient of the 24 receiving glutathione, but 16 of 18 patients receiving placebo, had developed neuropathy symptoms. Again, a trend toward greater tumor response (76%, compared to 52% in controls) was seen with glutathione treatment.152 An open trial with 79 ovarian cancer patients found i.v. administration of 2500 mg glutathione prior to treatment with a cisplatin / cyclophosphamide combination led to greater tumor response and reduced toxicity compared to that found in other trials using these chemotherapeutic agents.153 Another trial using the same glutathione dose with the same combination chemotherapy found no cases of nephrotoxicity in 20 patients. The authors reported, based on their experience, that the effect of the chemotherapy was not interfered with, and may have been enhanced.154 These results have not been followed up in controlled trials, however. The interactions between glutathione and chemotherapy agents other than cisplatin and cyclophosphamide have not been explored in human trials. Alternative Medicine Reviews, 1999;4(5):304-329 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.