Disease-Free from Malignant Glioma after Cotara

A congratulatory email I sent to Dr. Patel at Med. Univ. of S.C.:

Oct. 10, 2005
To: Dr. Sunil Patel, Dept. of Neurological Surgery, MUSC
cc: Holly Auer, Charleston Post & Courier
cc: Dr. Henry Brem, Chairman, Scientific Res. Ctr., NABTT
cc: Dr. Stuart Grossman, Project Leader, NABTT
cc: Dr. Robert Lustig, Abramson CC, UPENN M.C.
cc: Dr. Randy.Jensen, Prof-Neurosurgery, Univ. of Utah
cc: Steven King, CEO, Peregrine Pharm.

Subj: Article, “MUSC Therapy Promising – 3.5 Years Later, Study Participant Shows No Sign of Brain Tumor”
By: HOLLY AUER - hauer@postandcourier.com
The Charleston Post & Courier - June 17, 2005
Link: http://archives.postandcourier.com/archive/arch05/0605/arc06172381169.shtml

Somehow Ms. Auer’s article this past June about Mr. Freddie Sanford’s Cotara miracle slipped under my radar (See Full Text below). This brave survivor is disease-free from brain cancer 3.5 years after Cotara treatment at the Med. Univ. of S.C. (MUSC) by Dr. Patel’s group. THANKS and CONGRATULATIONS to you Dr. Patel, and the other Cotara Ph2 PI’s, for laying the foundation, and BEST OF LUCK to the NABTT ( www.nabtt.org ) with FDA-Approved “Product Reg. Trial” which began 8-29-05 at 4 NABTT sites: Wake Forest Univ., Emory Univ., Univ. of Alabama at Birmingham and Univ. of Pennsylvania, Dr. Lustig of UPENN as PI.

8-29-05: NABTT Initiates Cotara Brain Cancer Trial at 4 sites:
http://www.investorshub.com/boards/read_msg.asp?message_id=7533714
NABTT Trial info: http://www.nabtt.org/protocols.htm#D
NCI Trial info: http://www.clinicaltrials.gov/ct/show/NCT00128635

Sincerely,
C.J.Gaddy, St. Simons Isl., GA

“MUSC Therapy Promising – 3.5 Years Later, Study Participant Shows No Sign of Brain Tumor” - The Post & Courier, Charleston, S.C.
Jun 17, 2005, by: HOLLY AUER - hauer@postandcourier.com
http://archives.postandcourier.com/archive/arch05/0605/arc06172381169.shtml
For nearly two years, the tumor in Freddie Sanford's head beat back every treatment doctors threw at it. Then he learned about a new surgically implanted medicine-delivery catheter that promised to cross the stubborn blood-brain barrier that makes treating brain diseases so tough.

He grabbed at the chance to join the Medical University of South Carolina study that was testing the new treatment. Days later, Sanford sat in a hospital bed as a lead box dripped radioactive poison into his brain, dispatched in hopes of destroying the tumor. Having exhausted the reach of surgery, radiation and chemotherapy, it was his last chance.

Three and a half years later, at 46, Sanford's still alive, making him a member of a very small group. A diagnosis of malignant glioma — the most common type of brain tumor that afflicts 9,000 people in the United States each year — is widely considered a death sentence. Without treatment, patients usually succumb within weeks, and only 4% live more than 5 years after their diagnosis.

Sanford already has passed that threshold, and scans of his brain show there's no tumor left. He was one of 51 patients to be treated over the past seven years at MUSC in a study with a "convection-enhanced delivery" of a drug called Cotara, the results of which are published in the new issue of the medical journal Neurosurgery.

The researchers, led by professor and clinical chairman of neurosciences Dr. Sunil Patel, found that survival rates jumped to about 10% when patients were treated with the catheter technique and the new drug, which has been fast-tracked for approval by the U.S. FDA. To patients such as Sanford, those statistics mean the difference between resignation to death and reason to hope.

"It is scary, but when you're a cancer patient, you want to try everything," Sanford said, recalling his awe at sitting in a hospital room where everything was covered in plastic, his family forced to wait outside because his treatment was so toxic.

The Cotara research adds to a brain-cancer treatment arsenal that includes implantable chemotherapy wafers and balloons filled with radioactive medicine, all considered "little tiny baby steps" in the fight against a relentless disease, said Dr. Joseph Jenrette, professor and chairman of department of radiation oncology at MUSC.

The new treatment is especially novel because it links the ever-expanding field of drug development to the more sluggish research on drug delivery. "We were getting fancier and fancier molecules to treat with, but they were designed in labs and we had no way of giving them," Patel said. "Now we know we can."

By the time Sanford joined the Cotara study, his tumor had already robbed him of his ability to drive, his life at work as a civil engineer for Santee Cooper and his biking and sports games with friends. He was besieged by bizarre seizures that took the form of awful tastes and smells, fainting spells and horrible weakness.

Doctors already had removed a big chunk of the right temporal lobe of his brain, but again and again, the tumor grew back. His doctors hadn't talked much about the odds since he was first diagnosed, but he knew after two recurrences, his chances for survival were bleak.

At his last check-up, though, Sanford was told some words few brain cancer patients dare to even entertain: "I think you've beat the cancer," Patel told him.

The Cotara findings are expected to have use for many other brain diseases, including mental illness, a field where existing drugs are besieged by troublesome side effects and safety concerns. "This paper is sort of a landmark because it proves this technology works and is safe for the patient," Patel said. "It really opens the door for treating other diseases that involve the brain."

In the past, drugs used to battle brain tumors didn't penetrate the blood-brain barrier, which protects the brain from toxins floating through the bloodstream. Consequently, the medicine led to nasty side effects — hair loss, vomiting, diarrhea and constant weakness — with none of the intended benefit.

At most, Patel said, the drugs gave patients an extra week or two of life. Patients who got the Cotara treatment through a catheter implanted in the brain, however, got a uniquely targeted treatment. They reported few side effects, and the tumors disappeared altogether in a third of the surviving patients.

In a world where doctors must bargain with an almost certain death when designing treatments, that's a significant leap, Jenrette said. "We're still looking for the miracle in this," he said. "We try to be fair and honest when dealing with disease that's not fair and honest. This is a disease that you wouldn't wish for your worst enemy."
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6-1-05: Cotara w/CED Brain Delivery pub. in Neurosurgery Journal:
”Cotara Holds Promise for Treating Brain Cancer - P1/P2 Data Suggests Extended Survival in a Number of Patients"
http://ir.peregrineinc.com/phoenix.zhtml?c=74236&p=irol-newsArticle&ID=715495

June 2005: “Safety and Feasibility of Convection-enhanced Delivery of Cotara for the Treatment of Malignant Glioma: Initial Experience in 51 Patients”
Neurosurgery. 56(6):1243-1253, June 2005.
http://www.neurosurgery-online.com/pt/re/neurosurg/abstract.00006123-200506000-00009.htm
Patel, Sunil J. M.D.; Shapiro, William R. M.D.; Laske, Douglas W. M.D.; Jensen, Randy L. M.D., Ph.D.; Asher, Anthony L. M.D.; Wessels, Barry W. Ph.D.; Carpenter, Susan P. Ph.D.; Shan, Joseph S. M.P.H.
Abstract:
OBJECTIVE: We report the safety and feasibility of using convection-enhanced delivery to administer Cotara (Peregrine Pharmaceuticals, Inc., Tustin, CA), a novel radioimmunotherapeutic agent, to patients with malignant glioma.
METHODS: Between Apr. 1998 and Nov. 2002, 51 patients with histologically confirmed malignant glioma received Cotara by convection-enhanced delivery. Most patients (88%) were treated with Cotara targeting tumor volume-dependent, single or multiple administrations of activity ranging from 0.5 to 3.0 mCi/cm3 of baseline clinical target volume. Two weeks after infusion, single-photon emission computed tomographic imaging determined the spatial distribution of Cotara. Patients were followed for as long as 41 months (average follow-up, 5 mo). Safety was evaluated on the basis of incidence of procedure-related, neurological, and systemic adverse events. Feasibility was evaluated in a subset of patients on the basis of the correlation between the prescribed activity and the actual activity administered to the targeted region.
RESULTS: 51 patients, 37 with recurrent glioblastoma multiforme, 8 with newly diagnosed glioblastoma multiforme, and 6 with recurrent anaplastic astrocytomas, were treated. Average tumor volume was 36 +/- 27.6 cm3 (range, 5-168 cm3). Of the 67 infusions, 13 (19%), 52 (78%), and 2 (3%) delivered less than 90%, 100 +/- 10%, and more than 110%, respectively, of the prescribed administered activity to the targeted region. Treatment-emergent, drug-related central nervous system adverse events included brain edema (16%), hemiparesis (14%), and headache (14%). Systemic adverse events were mild. Several patients had objective responses to Cotara.
CONCLUSION: The majority of Cotara infusions delivered between 90 and 110% of the prescribed administered activity to the targeted region. This method of administration has an acceptable safety profile compared with literature reports of other therapeutics delivered by convection-enhanced delivery.

NABTT Cotara Trial info: http://www.nabtt.org/protocols.htm#D
NCI Cotara Trial info: http://www.clinicaltrials.gov/ct/show/NCT00128635

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PS: The remarkable story of JEROD SWAN, who was treated with Cotara/TNT for Brain Cancer several years back. Hopefully he’s still alive, I’ve prayed often that he is. If you haven’t seen this, I think you’ll enjoy the read:
From KSL TV, April 19, 2002
http://web.ksl.com/dump/news/cc/uthealth/tumor.htm

“Experimental Drug Targets Brain Tumors”

A new experimental drug dubbed TNT acts like a smart bomb, which targets and destroys brain tumors without damaging normal cells. The University of Utah, along with 5 other medical centers, are about to begin the third stage of clinical trials on the compound. Science Specialist Ed Yeates shows us how it works.

Cotara is a molecule with two arms. One holds a radioactive substance, while the other searches out and grabs a hold of ONLY tumor cells. Once attached, the radiation, like dynamite, goes off.

Randy Jensen, M.D. / University of Utah Neurosurgeon: AND WE INFUSE IT SLOWLY OVER A COUPLE OF DAYS AND AS THE DRUG FILTERS THROUGH OR GOES BY THESE TUMOR CELLS, IT STICKS TO THE TUMOR CELLS AND GOES PAST THE NORMAL CELLS.

Jerod Swan, 24, from Vernal, Utah, was diagnosed with a brain tumor more than 4 years ago. He was one of 40 patients among five medical centers who got the infusion during phase II trials. His brain tumor was destroyed and has not returned.

JEROD SWAN, PATIENT: EVERYTHING I AM AND ALL I DO NOW IS BECAUSE OF IT YOU KNOW - AND I'M JUST VERY THANKFUL TO BE ALIVE.

Destroying brain tumors is not easy. But while even this drug does not succeed in all cases as it did with Jarod, it's a rare tool right now in the hands of neurosurgeons.

DR. JENSEN: MOST OF THESE DON'T EVEN WORK IN ANIMAL STUDIES AND THEY GET STOPPED WELL BEFORE THIS STAGE. TO MAKE IT INTO HUMAN TRIALS IS REALLY QUITE REMARKABLE.

The drug apparently has very few side effects. Even while its searching and destroying tumor targets, patients - as in this case - remain alert, talking to their families.

ED YEATES, SCIENCE SPECIALIST: NOW AS THE UNIVERSITY BEGINS STAGE III CLINICAL TRIALS, NEUROSURGEONS WILL SEE IF COTARA PROVES TO BE MORE EFFECTIVE ON PATIENTS WHO ARE IN THE EARLIER STAGES OF THEIR CANCER. ED YEATES, EYEWITNESS NEWS, SALT LAKE CITY. - April 19, 2002
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