Thursday, June 10, 2010

CCNU and Treating Canine Brain Tumors

On December 23, 1971, President Richard Nixon signed the National Cancer Act. This was soon designated as our national "War on Cancer". This act opened the door and financed a massive review of drugs synthetic and natural that might produce a positive result in the treatment of cancer. In response to this effort a massive amount of review material was generated that was available to the public at the NIH library in Bethesda, Maryland.

As we solidified our meager knowledge about brain tumors in dogs, Dr. Lisa Fulton, our gifted oncologist, and I realized that if we were going to attack these tumors, we would have to better establish the same multi-modal techniques available in human medicine. We had been performing CT scans since 1977 and MRI's since 1984. Being very selective with our cases, we were able to define intracranial masses with a new degree of certainty. We approached tumor removal and biopsy with trepidation but early post-operative surgical results were quite encouraging. Realizing that man and dog were quite different when surgical planning was on the table was quite a fascinating lesson. Radiation therapy was not readily available but was developing in the private veterinary sector quickly. It was available enough for us to call upon it if we thought this was the best choice. What we were missing was that chemotherapeutic agent that penetrated the blood brain barrier with manageable toxic side effects. All of the currently available agents did not penetrate this biological impasse that so carefully guarded the brain's home.

Fortunately President Reagan's act to remove cancer from the face of the earth put a huge amount of readily available knowledge in one place. Whenever I could get away from my growing Specialty Hospital (Veterinary Referral Associates, Inc., in Gaithersburg, Maryland), I went down to the hallowed halls of the NIH library in Bethesda and read article upon article about medicinals of all types, many of which would be explored and abandoned and never be heard of again. During one of these sojourns, I came across a drug called BCNU or Carmustine. Bis-chloronitrosurea is a nitrosurea that is actually related to "Mustard Gas" an agent used by the Germans against the British and French during World War One. Mustard Gas' nephews and nieces would in a peculiar turn of events become key players in the "War on Cancer"? There in Bethesda, I found that some of the original research on BCNU was performed on the dog and there was substantial information that it crossed the blood brain barrier. Not only were these effects exactly what we were looking for but it also had an oral analog, CCNU or Lomustine that could be administered in pill form. To develop treatment protocols from the available research was kind of like trying to guess how much weight a bridge can hold by jumping up and down upon it. The fact is that most of the dogs we wanted to treat were going to die in a few months without treatment and the owners were always made aware of our ignorance. Starting in about 1983, Dr.Fulton and I determined a dosage protocol that was well tolerated and at least by anecdote seemed to extend our patient's lives. The real breakthroughs were to come when we had biopsy material and long-term followup, with autopsies, once our patients died. In the world of veterinary medicine these numbers are always small. Our ability to pull multiple centers together to get real statistically relevant numbers has been stymied by our culture.

In 1990, Lisa and I published the first paper on the use of CCNU in the dog. It continues to be one of numerous primary chemotherapuetics used in dog cancer treatment today. It has a significant place in the treatment of canine brain tumors.

We have yet to erase the frustration of treating canine brain tumors but we certainly have one more bullet in our arsenal.


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