It was two years ago that I first began talking with Dr. Kaelin about possible participation in a clinical trial. I am forty-one years old. I have had six brain surgeries and one on my cervical spine. My right arm is partially paralyzed -- it moves, but I have no clear idea of where it is, and I can’t trust its grip. My pancreas is completely displaced with cysts, causing me serious digestive issues. And of course I have a number of small brain and spinal tumors, and a couple of kidney lesions . . .

The most worrisome tumor is one the size of a grape in the ventricle area of my brain. It does not cause symptoms, and it has room enough to grow to the size of a pecan before it causes me any problems, but it’s in the thinking area of the brain so I really would like it not to grow at all. I would really love to avoid any more surgery. I’d love to have a drug that would keep these tumors from growing. Shrinkage would be ideal, but I’d settle for keeping them just the way they are. But even if it didn’t help me -- even if I could only help them learn the pros and cons of a new drug and develop a better one for my daughter and other young people coming along
-- I would be glad to have contributed to our knowledge and hopefully helped to lay the groundwork for the right drug in the future.

It was in that spirit that I approached Dr. Kaelin and began the process of enrolling in his clinical trial. We began the interviewing process by phone and fax. And in the midst of it all the drug company cancelled the trial. They had discovered some potential long-term negative effects in their testing on dogs that they did not like, so they "pulled the plug" on the trial.

The sense of devastation was intense. It felt like shattered hope. But then in discussing it with friends I realized that they had done the right thing. As great as my disappointment was, how much worse would it have been to take a drug and have some awful side effect that worsened my health? I had to be grateful that they had the honesty to admit up front that this drug was not yet right. Dr. Kaelin assured me that there were other drugs "in the pipeline" -- it was as if they did not yet have quite the right recipe, but they were still working on a number of similar drugs, and were using this same technology to check for long-term effects before they got to human trials. It was disappointing, but in another sense also comforting.

In January 2003 Dr. Dan George of Dana-Farber Cancer Institute, working in collaboration with Dr. Kaelin, called me to say that the drug was now ready to go, and they were carefully approaching clinical trials. Additional studies suggested that the side-effects seen with long term administration in some animal species was unlikely to translate into humans. Phase I trials have gone well, and Phase II trials with prostate and kidney cancer are encouraging.

He asked if I would go through the evaluation process, to see if I would qualify. They had to make sure that any issues that needed surgery were taken care of first, and that I met all the other criteria. He needed copies of records and scans, family history, hours of detailed interviews by phone. In addition, I would need to go to Boston for two and a half weeks of onsite tests. If I qualified, they would send me home with the pills, but I would need to come to Boston once a month for a year.

It was a big commitment of time and money too. I talked with my family and my pastor, and prayed about it. I also spoke with my neurosurgeon. Dr. Sanford, a pediatric neurosurgeon, has done every one of my brain and spinal surgeries since I was nineteen. He read over the protocol and said he thought it was a good idea. If this drug could postpone another surgery, or keep me from needing it at all, it would be a blessing. He immediately wrote a letter to Dr. George, recommending me for the protocol and offering his cooperation.

My daughter clinched it. "What if this drug helps you to feel better and never have any more surgeries and live to be a great grandmother?"

With the backing of my family, my surgeon, and my friends, I began to tackle the logistics. Through the VHL Family Alliance I got the name of Mercy Airlift (see following article). They asked if this transport was needed for a life-threatening condition. We said yes. They organized free airplane tickets for myself and my father to travel to Boston for the evaluation. Mercy will help once every six months, and Southwest has low-priced fares to Hartford or Providence. My grandmother lives in Hartford, Connecticut, and we thought we could commute from there. VHLFA volunteers in Boston offered housing if we wanted it. So off we went to the big city.

We arrived February 6, and were greeted by a snowstorm. Commuting 100 miles from Mississippi to Memphis is one thing. Commuting 100 miles from Hartford to Boston in February is another thing altogether. We commuted from Hartford for three days and were totally exhausted before we accepted the offer of Boston-based housing during the week, and drove back to Hartford for the weekends. February broke snowfall records in Boston -- more than 30 inches of snow fell during my visit.

It was quite an adventure at the hospitals too. There are five hospitals in the Harvard Cancer Center -- Dana Farber Cancer Research Institute, Joslin Diabetes Center, Brigham & Women’s Hospital, Beth Israel Deaconess Hospital, and Massachusetts General Hospital (MGH). Each one is doing the detail work on one part of the research. I had tests at each. Four of the five are in the same part of town, just blocks apart. The MGH testing was done in Charlestown, not far from the U.S.S. Constitution, the oldest ship in the U.S. Navy, launched in 1812.

The testing was similar to the routine I went through at NIH. They did thorough tests on every part of my body, making sure they had a detailed record of every bit of VHL involvement. Most tests were the standard VHL clinical tests, but when they came to a tumor they intend to track for the study, they switched to the "research routine" which is a much more painstaking analysis of the tumor, its size and characteristics, and in particular the blood flow to and from the tumor. This meant longer MRIs. For the spinal MRIs they had a television mounted inside the tube showing a movie with subtitles to help pass the time.

I guess the most important thing it takes to be part of a clinical trial is patience. You have to be flexible, be on call, and roll with changes in the scheduling. It’s a trial, after all, and I was the first patient in the trial, so they were learning as they went along. One day they called and asked me to come a day earlier than planned, another day they asked me to stay home and come the following day. I kept my senses of humor, curiosity, and adventure too, and chatted with the staff or whatever other patients were nearby. I met some lovely people. I learned a lot too. The radiologist went over the results with me immediately following the scans, and I got to watch the G.I. test on the monitor. Everyone was very nice and clearly highly skilled. Everyone from the nurses to the maintenance people assured me I was in "the best place." On Valentine’s Day I found a card my husband had tucked into my suitcase, full of love and hope.

Half-way through the testing, they called to say we had hit a snag. My metanephrines were 291. According to the protocol, participants’ meta-nephrines must be no higher than 290. I sat out the day waiting for them to get clearance from the drug company to proceed at this level. It seemed an insignificant deviation to me, but in order for the data from the study to be meaningful, they have to follow the protocol exactly. They did get approval, but it was an anxious day for me. To come all this way and be ruled out for one stinking point! But then it was resolved and we proceeded.

So at the end of two weeks of testing, I am officially enrolled in the study! I start the drug on Monday, have MRIs Tuesday and Wednesday, and then go home with the pills. Five pills a day, stay away from grapefruit, and come back in a month. They want my local doctors to do some blood tests in between and fax them the numbers, and they’ll see me in March. It will take a full year to get the final results from this trial, and meanwhile there are other trials going on with other drugs. It seems a long time since our whole family sat with Dr. Zbar’s researcher the 1990, drawing blood from everyone in the room to try to locate the genetic cause of VHL. But at last we are seeing some potential therapies emerge from all the research! I hope to have some very good news to share next year!

Dr. George is accepting VHL patients who have asymptomatic CNS hemangioblastomas (hB) and have had at least one prior neurosurgical procedure and do not currently require surgical intervention, OR have symptomatic CNS hB which can not be successfully treated with standard therapy, OR have retinal hB causing impairment in visual function (visual acuity, contrast sensitivity, visual field, or color vision), which cannot be successfully treated with standard therapy. If you are interested in exploring this further, please call Judy or Stephanie at 617-632-5068. Eligibility criteria are listed at

http://clinicaltrials.gov/ct/gui/show/NCT00052013?order=1

As printed in the VHL Family Forum 11:1, March 2003. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org.