RECENT TM RELATED NEWS:
January 2005: Phase I/II trial of TM for Pulmonary Fibrosis Coalition for Pulmonary Fibrosis Awards $60,000 Research Gift to University of Michigan Health System for Pulmonary Fibrosis.
December 2004: TM Patent Appliation by Brewer and associates. Very detailed - suggests that TM might achieve copper lowering in 2 weeks.
September 2004: A list of some Pharmacies that sell TM
September 2004: 3 recent TM related research abstracts
August 2004: Ivanhoe interview with George Brewer, M.D. nine phase 2 cancer studies going on using TM.
May 2004: Phase II trial of copper depletion as angiosuppressive treatment in newly diagnosed Glioblastoma Multiforme: Final report: copper depeletion using Penicillamine in conjunction with radiation was not effective.
May 24, 2004: PRESS RELEASE: Attenuon Announces Launch of ATN-224 Phase I Trial in Patients With Solid Tumors ATN-224 is a second generation version of tetrathiomolybdate, a compound licensed from the University of Michigan. ATN-224 has been shown to inhibit tumor angiogenesis and growth in pre-clinical models.
September 10, 2003: PRESS RELEASE: University of Michigan Drug developed for rare disease may help millions more as treatment for cancer, autoimmune diseases UMHS researchers leading dozens of studies on anti-angiogenesis drug
June 22, 2003: American Society of Clinical Oncology - 2003 Abstract A pilot trial of irinotecan, leucovorin, and 5-fluorouracil (ILF) combined with the anti-angiogenesis agent tetrathiomolybdate (TM) in metastatic colorectal carcinoma (MCRC) by Gartner, S. D. Merajver, Q. Pan, K. Griffith, G. Brewer, G. Hejna, M. Zalupski; The University of Michigan, Ann Arbor, MI.
May 23, 2003: PRESS RELEASE: Maine Medical Center Copper Chelation is a Promising New Therapy for Clogged Arteries - International Team Discovers that Blocking the Function of Copper Prevents Renarrowing of Arteries. Also see press release from Dartmouth Medical Center: Copper Chelation Holds Promise for Clogged Arteries, Team Finds
January 2003: NIH: NCRR Reporter
Research Highlights: Copper Deficiency Starves Tumors
Quotes from Dr. Brewer: “I expect that TM will be very effective in treating cases of metastatic cancer in which the tumors are still small.” “I think that TM has great potential for use with other agents, particularly if those agents reduce tumor size. Under those conditions, I think that TM will have a significant role in preventing regrowth.”
September 13, 2002: TM STATUS: TM is expected to get FDA approval for use in Wilsons disease within 2 years. Then it could be used "off label" for cancer. TM is now available from some compounding pharmacies with a doctor's prescription. TM alone may not be effective on tumors larger than about 2 mm (0.08"). TM appears to work synergistically with chemo and radiation. TM combined with low-dose chemo may be effective. Several Stage II TM trials are nearing publication.
September 11, 2002: PRESS RELEASE: September 6, 2002 from University of Michigan Laboratory study explains clinical promise of anti-angiogenesis cancer drug
August 28, 2002: AUDIO TAPE: You can order an audio tape about the January 2002 state of the art in TM research from National Audio & Video. The tape is of a talk by Brewer and Merajver at the January 2002 Nutrition Week conference and is entitled Angiogenesis, Cancer, and Copper. It costs $12.00 and is Tape Number: 10-02-89. Search for "Angiogenesis" in the list of conference talks to find the tape. You can also order by phone: 1.800.373.2952 or 303.292.2952 (9-5 MST) or by email at email@example.com
EMAIL LIST: There is a restricted membership Yahoo email list CuZnMail devoted to the discussion of issues related to copper reduction as a cancer therapy. For instructions on how to join the CuZnMail list, please email the list owner.
The purpose of this web page is to share some information on the use of the industrial chemical ammonium tetrathiomolybdate (TM) for treating many cancers. Recent medical research suggests that TM can be ingested to reduce the levels of copper in the body to a level that is adequate for normal health, but low enough to reduce the excess blood vessel growth that cancers require for growth. TM appears to have few side effects, and quality of life is reported to be high in comparison to most chemotherapies. I am not a doctor, or a medical researcher, but I have some recent direct experience with this new treatment, and I believe that my information may be useful to others in similar circumstances.
Under normal circumstances I would not seriously consider attempting do-it-yourself cancer treatment, but my recent experience suggests to me that that there are situations where it is a reasonable alternative. Desperate situations require desperate measures.
At any given moment there are thousands of people with cancers that have resisted the best treatments available, and their prognosis can be extremely poor. Recent advances in medical science suggest that major improvements in cancer treatment may be only a few years away, but it is unlikely that some patients can survive that long. For those patients, a treatment that might halt the progress of the cancer would be very helpful. TM treatment may offer some hope for this type of treatment.
MY EXPERIENCE WITH TM:
Here is my experience. In the fall of 1998 my twin brother Richard Saum was diagnosed with one of the worst types of brain cancer, GBM IV, and he was given about one year to live. He took advantage of the best medical treatment available including surgery, radiation and chemotherapy but none of these treatments offers a cure at present. As his condition grew worse, my family studied new medical research for potential breakthroughs, and we found one possibility in the work of Dr George Brewer at the University of Michigan. This work was described in a number of popular articles such as:
Then a medical journal article came out on TM therapy to stop solid tumor growth.
Preclinical and in vitro studies have determined that copper is an important cofactor for angiogenesis. Tetrathiomolybdate (TM) was developed as an effective anticopper therapy for the initial treatment of Wilson's disease, an autosomal recessive disorder that leads to abnormal copper accumulation. Given the potency and uniqueness of the anticopper action of TM and its lack of toxicity, we hypothesized that TM would be a suitable agent to achieve and maintain mild copper deficiency to impair neovascularization in metastatic solid tumors. Following preclinical work that showed efficacy for this anticopper approach in mouse tumor models, we carried out a Phase I clinical trial in 18 patients with metastatic cancer who were enrolled at three dose levels of oral TM (90, 105, and 120 mg/day) administered in six divided doses with and in-between meals. Serum ceruloplasmin (Cp) was used as a surrogate marker for total body copper. Because anemia is the first clinical sign of copper deficiency, the goal of the study was to reduce Cp to 20% of baseline value without reducing hematocrit below 80% of baseline. Cp is a reliable and sensitive measure of copper status, and TM was nontoxic when Cp was reduced to 15-20% of baseline. The level III dose of TM (120 mg/day) was effective in reaching the target Cp without added toxicity. TM-induced mild copper deficiency achieved stable disease in five of six patients who were copper deficient at the target range for at least 90 days.
I showed the article to my brother's doctors and they agreed that the treatment was unlikely to harm him and they prescribed the blood tests that would be necessary to track the TM treatment progress. At that time TM was not available for medical use. I obtained some reagent grade TM (ammonium tetrathiomolybdate) from a chemical supply house and weighed it into the required doses. Unfortunately he did not have the 2-3 months that it typically takes for TM to lower copper levels to the recommended 20% of baseline copper levels as measured by the marker levels of serum ceruloplasmin (Cp).
Before starting TM, both my twin bother and I had our Cp levels tested: mine was 28 and his was 38 (36% higher than mine) Note that copper is so pervasive in most foods that it is impossible to reduce copper levels by diet alone. Liver and shellfish are the only foods that should be avoided by patients trying to lower their copper levels.
Here is the Cp tracking from my brother until he died. He had weekly blood draws and we had no problem with getting a prescription to add Cp and hematocrit (Hct) tests weekly. Hct is tracked to make sure that the TM is not causing anemia:
The data above shows that it took my brother almost a month to get down to my (normal) Cp level. Note that TM does not appear to be successful in lowering copper levels in all patients. And there is no published data of its results against brain tumors. But according to the theory, it should work on all cancers tumors.
I found that Dr Brewer's Stage I Trial of TM article had all the information I needed to use TM. I do not know if there are more recent papers on TM. I contacted Dr Brewer for help but he did not provide any assistance. Fortunately his paper is quite comprehensive.
There is an excellent recent TM how-to article
We had no trouble getting our doctors to assist us with TM therapy by providing the necessary prescriptions. We showed them all the information we had and they did not see how it could harm him. I myself took TM for a few weeks to see its effects, and the only side effect I experienced was black stools as the TM drew the copper out of my body.
Here is my rationale for trying TM:
I only wish that we had found out about anti-angiogenesis treatments like TM earlier when my brother was still healthy and had the time required to get his copper level down to the recommended level. I would suggest that everyone in similar circumstances should consult with their doctor about adding a copper reduction technique to their cancer treatment program.
Pace of TM Research? Since TM is an industrial chemical that was not invented and patented by a drug company, there appears to be little incentive for private funding of research on TM as a cancer treatment. Without market competition we should only expect government research, and if there are no political pressures, then we might expect rather slow progress in future TM related research.
Third World Chemotherapy? Of the six billion inhabitants on planet earth, about 2 billion live on less than $2 per day, and about 1 billion live on less than $1 per day. Any cancer treatment for these people would have to cost less than $1 per day and require little or no assistance by medical professionals. I think a case can be made that TM might be an important part of a solution to this problem. Today TM is available from some US pharmacies for about $300 for a one month supply or $10 per day. However, TM can be obtained from chemical supply companies like Strem Chemicals or Sigma Aldrich in 99.9% pure form of ammonium tetrathiomolybdate for about $10 per gram. Of course they do not sell it for human consumption. However, if we assume that human grade TM could be made and distributed in the third world for about the same price, and the typical daily dose is 120 mg, then the daily cost of TM could be about $1 per day. Perhaps the third world has more incentive than the first world to perform the clinical trials necessary to establish the efficacy of TM as a treatment for cancer?
RECENT NEWS AND CONFERENCES (LAST UPDATED SEPTEMBER 11, 2002):
September 6, 2002 Press Release from University of Michigan Laboratory study explains clinical promise of anti-angiogenesis cancer drug
PAPER in Neoplasia 2002 Sep-Oct;4(5):373-9
Suppression of Tumor Recurrence and Metastasis by a Combination of the PHSCN Sequence and the Antiangiogenic Compound Tetrathiomolybdate in Prostate Carcinoma.
Van Golen KL, Bao L, Brewer GJ, Pienta KJ, Kamradt JM, Livant DL, Merajver SD.
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0948, USA.
Plasma fibronectin-mediated invasion of human DU145 prostate cancer cell line was efficaciously inhibited in a rat tumor model by treatment with Ac-PHSCN-NH(2) peptide. Invasion of DU145 cells was stimulated by the PHSRN sequence of plasma fibronectin. However, PHSCN acts as a competitive inhibitor of PHSRN-mediated invasion. In the current study, we determined whether PHSCN could inhibit the recurrence and metastasis of DU145 tumors after excision of the primary tumor in an athymic nude mouse model. We demonstrated that mice treated thrice weekly with intravenous Ac-PHSCN-NH(2) peptide survived tumor-free for more than 30 weeks post-primary tumor excision, whereas their untreated counterparts succumbed to recurrence and/or metastatic disease in significantly less time. Because of the universal requirement for angiogenesis in solid tumor growth, we tested the efficacy of copper deficiency induced by tetrathiomolybdate (TM) to retard tumor growth in the Dunning prostate cancer model. Significant reduction in size of the primary tumor was observed in mice rendered copper deficient. We sought to reduce tumor growth at the primary and metastatic sites by combining the anti-invasion Ac-PHSCN-NH(2) peptide with TM. Improved survival, fewer metastatic lesions, and excellent tolerability were observed with the combination therapy.
PAPER in Neoplasia 2002 Mar-Apr;4(2):164-70
Radiotherapy and antiangiogenic TM in lung cancer.
Khan MK, Miller MW, Taylor J, Gill NK, Dick RD, Van Golen K, Brewer GJ, Merajver SD.
Department of Radiation Oncology, The University of Michigan Medical Center, Ann Arbor, MI 48109-0936, USA. firstname.lastname@example.org
Tetrathiomolybdate (TM) is a potent nontoxic orally delivered copper complexing agent under development for the last several years for the treatment of Wilson's disease. It has been shown to block angiogenesis in primary and metastatic tumors. Therefore, the combination of cytotoxic radiotherapy (RT) and antiangiogenic TM could target both the existing tumor and the tumor microvasculature in a comprehensive strategy. Using a Lewis lung high metastatic (LLHM) carcinoma mouse tumor model, we demonstrate that the combination of TM and RT is more effective than either used as monotherapy. We also show that their therapeutic effects are additive, with no additional toxicity. We show that TM has no significant cytotoxicity in vitro against LLHM tumor cells, further supporting the antiangiogenic mechanism for its action.
AVAILABILITY: TM is available from compounding pharmacies with a doctors prescription, although it is not an FDA approved drug for any disease yet. It does have orphan drug status.
One compounding pharmacy that offers TM at a discount to CuZnMail list members is:
Wayne Loveland, pharmacist
The Prescription Center
1907 West Avenue South
LaCrosse, WI 54601
toll free 800-203-9066
Email: Wayne Loveland.
Attenuon LLC is a San Diego-based pharmaceutical company that has obtained rights to TM from the University of Michigan and is working on FDA approval for TM's use as a cancer treatment. FDA approval for use of TM for Wilson's disease could come within the next year or two. (from Brewer's talk at Nutrition Week 2002)
Kerbel on Angiogenesis from March 1, 2002 BIOWORLD Today.
Nutrition Week 2002 February 23-27 in San Diego, CA. Brewer and Merajver spoke on Angiogenesis, Cancer and Copper. Audio tapes are available - search for "Angiogensis" in the list of tapes.
ISTERH International Society for Trace Elements in Humans.
Program for 2002 Conference in Quebec City, Canada, September 15-20***POSPONED DUE TO 9/11***, 2001.
Brewer, Brem, Kerbel and Merajver will probably speak in the rescheduled 2002 conference.
SOME LINKS I FOUND HELPFUL:
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COPPER REDUCTION EMAIL LIST
There is a restricted membership Yahoo email list CuZnMail devoted to the discussion of issues related to copper reduction as a cancer therapy. For instructions on how to join the CuZnMail list, please email the list owner.