LOS ANGELES, CALIFORNIA (PRWEB) September 02, 2003 –- "Targeted Etanercept for Treatment-Refractory Pain Due to Bone Metastasis: Two Case Reports," is the title of a new medical article published in the August 2003 issue(volume 25, No. 8, 2003, pp.2279-2288) of the peer-reviewed medical journal Clinical Therapeutics and written by Edward Tobinick, MD, medical director of the Institute for Neurological Research in Los Angeles. The treatments were conducted at the private INR® without outside support or sponsorship. The full text of the article is available online at the journal website, www.clinicaltherapeutics.com, and will be accessible without charge for about the next 30 days.

"It is fascinating that this new therapeutic agent appears to have the potential to ameliorate not only the bone destruction that occurs in rheumatoid arthritis, but also the pain which accompanies bone destruction when certain cancers metastasize to the spine", said Dr. Tobinick. "The scientific basis for this new off-label use is experimental evidence that suggested that drugs of this class (TNF-alpha antagonists) may inhibit the biologic activity of osteoclasts(cells that lead to bone resorption), and that osteoclasts may be the mediators of malignant bone destruction. What came as a real surprise, however, was the rapidity, extent, and duration of the pain relief experienced by both treated patients."

The working hypothesis is that delivery of etanercept in anatomic proximity to the site of spinal metastasis ("targeted administration") results in a high local concentration of the drug, allowing it to have a therapeutic paracrine effect. It is postulated that TNF-alpha released by cancer cells stimulates osteoclasts to invade and resorb the surrounding bone, which results in release of tumor growth factors from the bone. Etanercept may interfere with this cycle by interrupting tumor-induced osteoclast activation.

Other recent pilot studies have also suggested that etanercept may have a role in cancer treatment (see abstracts presented at the American Society of Clinical Oncology meetings: abstract 83, 2002, "A phase II trial of etanercept, a tumor necrosis factor inhibitor in recurrent ovarian cancer" and abstract 2374, 2003, "Pilot study of recombinant human soluble tumor necrosis factor receptor (P75) fusion protein etanercept in patients with relapsed cutaneous T-cell lymphomas").

"The Clinical Therapeutics article presents preliminary, open-label results which require confirmation. Although it is premature to make any generalized treatment recommendations, further study is urgently called for, preferably utilizing a placebo-controlled, randomized, double-blind design, because of the unmet clinical need of this class of patients," said Dr. Tobinick.

A multi-center trial of etanercept administered systemically for the treatment of cancer-associated weight loss is currently underway (National Cancer Institute protocol NCI-P02-0232). In view of the dramatic clinical responses to targeted etanercept documented in this new article from the INR it is hoped that multi-center clinical trials under the auspices of the National Cancer Institute will be initiated without undue delay.

FURTHER BACKGROUND:

This potential new clinical use for etanercept joins other new, off-label uses of TNF-alpha inhibitors which have been discussed in recently published articles:

“Perispinal TNF-alpha inhibition for discogenic pain,” E. Tobinick and S. Davoodifar, Swiss Medical Weekly 2003;133:170-177. Abstract and full text at www.smw.ch.

“Targeted etanercept for discogenic neck pain: uncontrolled, open-label results in two adults,” E. Tobinick, Clinical Therapeutics 2003 April;25:1211-1218.

"Tumor necrosis factor-alpha antibody, infliximab, used to manage severe sciatica,” J. Karppinen, Spine 2003 April 15;28:750-754. Abstract and full text at www.spinejournal.com.

In addition, abstract OP0018 presented at the Annual Congress for European Rheumatology, EULAR 2003, on June 19, 2003, entitled "Efficacy of etanercept in the treatment of acute sciatica", authored by S. Genevay MD, S. Stingelin MD, and C. Gabay MD, from the Division of Rheumatology, University Hospital Geneva, Geneva Switzerland provides additional independent scientific support for the use of etanercept for the treatment of sciatic pain associated with disc herniation, a treatment modality pioneered by the INR in Los Angeles several years ago. In the U.S. this use of etanercept, detailed in several of the patents listed below, is licensed exclusively to the Institute for Neurological Research in Los Angeles.

The use of etanercept, infliximab and other recombinant DNA medications for the treatment of pain due to cancer metastasis to bone and other neurological disorders is protected by multiple U.S. patents and by a recently issued Australian patent, all of which have been awarded to Dr. Tobinick(see below). Please note that these medications have not been proven to be either safe or effective for these new off-label uses. These medications can have adverse effects. Please see the manufacturers' prescribing information for a discussion of approved indications and adverse effects.

Partial list of U.S. Patents awarded to Edward Tobinick, M.D.:

1. 6,015,557 Tumor necrosis factor antagonists for the treatment of neurological disorders. Filed March 23, 1999, issued January 18, 2000.
2. 6,177,077 TNF inhibitors for the treatment of neurological disorders.
3. 6,379,666 TNF inhibitors for the treatment of neurological, retinal, and muscular disorders.
4. 6,419,934 TNF modulators for treating neurological disorders associated with viral infection.
5. 6,419,944 Cytokine antagonists for the treatment of localized disorders.
6. 6,423,321 Cytokine antagonists for the treatment of sensorineural hearing loss.
7. 6,428,787 TNF inhibitors for the treatment of retinal disorders.
8. 6,471,961 Interleukin antagonists for the treatment of neurological, retinal and muscular disorders.
9. 6,537,549 Cytokine antagonists for the treatment of localized disorders, filed April 25, 2001, issued March 25, 2003.
10. Australian patent 758,523 Tumor necrosis factor antagonists for the treatment of neurological disorders, issued July 3, 2003.

This press release was issued by Edward Lewis Tobinick, MD, A Medical Corporation which conducts a private medical practice at the INR. Edward Lewis Tobinick, MD, A Medical Corporation is solely responsible for the contents of this press release. The contents of this press release are for educational purposes only and should not be construed as treatment recommendations for any of the clinical disorders discussed. Further information is available on the website: www.nrimed.com.