10 years of HOPE

10 years ago today, Gleevec was approved as a first line treatment for leukemia. What a revolutionary change that was! Targeted therapies have continued to be explored, allowing cancer to be attacked without significant toxicities to patients. Imagine how you would feel if you finally had HOPE again after a cancer diagnosis. That is what Gleevec did for so many!

http://www.cancer.gov/newscenter/pressreleases/2001/gleevecpressrelease

Read the original press release above.

The Birth of a Miracle

If you have ever wondered how a wonder drug like Gleevec gets developed, here is more ifnormation from one of the oncologists behind that drug.  This article made me think about the trial that Hans is entering for Ariad and the impact it may have on the future of CML treatment.

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November 3, 2009
A Conversation With Brian J. Druker, M.D.
Researcher Behind the Drug Gleevec
By CLAUDIA DREIFUS

Dr. Brian J. Druker, 54, an oncologist at Oregon Health and Sciences University and a Howard Hughes Medical Investigator, is one of three winners this year of the Lasker-DeBakey Clinical Medical Research Award, often called the “American Nobel Prize.” Dr. Druker shared the honor with Nicholas B. Lydon, a former researcher for Novartis, and Charles L. Sawyers of Memorial Sloan-Kettering Cancer Center, “for the development of molecularly targeted treatments for chronic myeloid leukemia, converting a fatal cancer into a manageable chronic condition.” Here is an edited version of a conversation that took place last month in New York:

Q. WHAT WAS LIFE LIKE FOR PEOPLE WITH CHRONIC MYELOID LEUKEMIA, OR C.M.L., PRIOR TO YOUR RESEARCH?
A. Life was pretty miserable. If you were over 40, the main therapy was interferon, which prolonged life for maybe a year in perhaps 20 to 30 percent of patients. Interferon made the patients feel awful — like the worst flu. The only other hope was a bone-marrow transplant for younger patients. The problem there was that the death rate in the first year was 25 to 50 percent.
C.M.L. patients were always difficult to see because both of us knew that the clock was ticking and there was virtually nothing that we could do about it.



Q. It must have been depressing to be an oncologist under those circumstances.
A. When I started my training in the 1980s, you rarely cured people. You felt, “if I can give my patient extra time, I’ve been successful.” But I could see there was a transformation of cancer treatment on the horizon thanks to breakthroughs in biochemistry and genomics. I wanted to be part of that, which is why I was a physician-researcher.
The way I’d been trained, cancer was seen as something like a light switch that was stuck in an “on” position. You were given a baseball bat, which was chemotherapy, and told to knock the light out with the bat. I thought, “Why don’t we just try to figure out why the light is stuck on, then we can fix it without breaking everything.”
So I started my laboratory career studying the regulation of cell growth — what turns the switch on, what helps it shut down. And that’s how Gleevec is different from earlier chemotherapies, which basically poisoned every cell in the body in an attempt to kill the cancer. Gleevec turned off the light switch and only killed the cancer cells.



Q. How did the idea behind Gleevec first come up?
A. By the late 1980s, C.M.L., though rare, was a cancer that scientists knew a lot about. We knew, for instance that a chromosomal abnormality existed in every C.M.L. patient. We knew that this abnormality created an enzyme that caused the uncontrolled growth of cancer cells. If you put this enzyme into animals, they got leukemia.
So in 1988, Nick Lydon, who led a drug discovery group at a pharmaceutical company that eventually became Novartis, came to talk to me. He was interested in developing drugs to block a family of cellular enzymes implicated in several cancers. I said to him: “If you want to develop targeted chemotherapies, C.M.L. is the disease to study. We know the most about it — and, if we can figure out a way to block this enzyme, we can turn off the cancer switch.”
So in Nick’s lab at the pharmaceutical company, he began screening for agents that worked on C.M.L. He’d send me his best compounds. I found one, STI571, that was better than the others; it would kill every C.M.L. cell in a petri dish. By 1995, STI571 was a lead compound set for clinical development.



Q. So Gleevec was on its way?
A. Not quite. Gleevec was a completely different class of drugs than what was used against cancer. Most researchers thought it wouldn’t work. Then, in 1996, before we were about to go to trials, Nick’s company merged with another, and he left. Gleevec was now caught in the changeover. I lobbied with the new executives. After some ambivalence, they agreed to go forward with Phase 1 trials. I think they felt it wouldn’t work and they could get rid of us afterwards.
But during clinical trials we saw this miracle: Once the patients were up to effective doses, we got a 100 percent response rate.



Q. Had that ever happened before in a clinical trial?
A. No. Never. You’d see patients where interferon wasn’t working, and they’d been issued a death sentence. Suddenly, all their hopes for the future were restored, and, with minimal side effects! This was around 1999, and the Internet chat rooms were just beginning. Patients in the trials began talking to each other like they’d never done before. I’d see a patient, and I’d read about it on the Internet that night: “few side effects,” “100 percent response.” Patients would come to me and say, “My doctor has never heard of this drug.” I’d never written it up. I hadn’t presented the data. Their doctors thought I was a charlatan. For a lot of people, Gleevec was simply too good to be true. But these once-dying patients were getting out of bed, dancing, going hiking, doing yoga. The drug was amazing.
Now the drug company had to make another decision. They hadn’t made enough drugs for a large-scale Phase 2 trial. But patients knew about Gleevec, and many more wanted to be included in the trials. Through the Internet, they generated a petition that landed on the C.E.O.’s desk, asking for greater access. That’s how Phase 2 was rapidly expanded.



Q. YOUR FRIEND AVICE MEEHAN OF THE HOWARD HUGHES MEDICAL INSTITUTE SAYS THAT YOU HAVE THE MOST AMAZING PERSEVERANCE. IS THAT WHAT IT TOOK TO MAKE GLEEVEC HAPPEN?
A. I think I’m more perseverance than smarts. There’s a basketball player who says, “Hard work beats talent when talent doesn’t work hard.” Well, I work hard. I understood that this project was too good to give up on. My patients needed me to do something to help them. I did everything I could by getting them a drug I thought would work.
When the drug looked like it was finally going to be approved, I was interviewed by a reporter from People magazine, Alexandra Hardy. She asked, “Who are your good friends?” I said: “I don’t have any. I work, eat, sleep, go to the gym.” She said: “You’re pathetic. You’ve got no balance in your life.”
Well, there is now. Alexandra and I got married, and we have three wonderful children.


Q. Gleevec was ultimately proved effective against two cancers, right?
A. Ten. It’s now F.D.A.-approved for 10. Gleevec went to market for a small disease, 50,000 patients, and it later got tested for other things. It’s now used by 200,000 patients worldwide.


Q. Do you see any of that?
A. I don’t see a penny, though that never was an issue for me. When I obtained the compound, it was already patented. I wasn’t going to get to test it if I tried to put my mark on it. I wanted to work on it because I thought it was going to be the way to treat C.M.L.



You know, my patients were people who’d been told “to get their affairs in order” because they were going die soon. And now some of them play with grandchildren they’d thought they’d never live to see. That’s worth more than money.

Thank You Novartis!

At his last doctor's visit, Tyler learned about a great program sponsored by Novartis, the manufacturer of both Gleevec and Tasigna. Apparently the company will actually cover some of the copay's for the next few months. While the copay is only $35 per month (thank goodness for medical insurance!!), we are still happy to have someone else pick up the bill for a few months.

Many of our readers may know someone else touched by blood cancers. If your friends/family are taking Gleevec or Tasigna, you might have them look into this copay assistance program too.

Where Should You Start if you are Diagnosed with Leukemia?

These are our thoughts of things to think about when diagnosed with leukemia, although many of these would apply to any serious illness:

1. Visit the Newly Diagnosed section of the Leukemia and Lymphoma Society website: http://www.leukemia-lymphoma.org/all_page?item_id=4221 They have checklists and information aimed at helping people in your shoes.

2. Find an oncologist who really listens to you and explains things to you in English. Then make sure you like his nurse, because you spend a lot of time with the oncology nurses!

3. Likely treatment that you would go on for leukemia are Hydrea (Hydroxurea) and Gleevec (for CML) or Induction Therapy (Cytarabine or Ara-C) (for AML or ALL). Tyler's been through both, so we can answer any questions you have about our experiences on those medications.

4. Take your medications carefully. Our doctors say that about 50% of people don't take the medication as prescribed, but it can make a big difference in the state of your disease.

5. Avoid any sports with a risk for contact until the doctor tells you your spleen is normal

6. Stay healthy otherwise - diet, exercise, adequate sleep.

7. Have someone other than each other that you can talk to. Sometimes it is easier to share your fears and frustrations with someone other than your partner.

8. Let family and friends support you. It takes a bunch of weight of your shoulders AND theirs! In fact, it sometimes is good to have a mental list of the things that others can do because many will ask and want to help in any way they can.

9. Remember that some people out there might be uncomfortable hearing about your illness. It's nothing personal; it's just that they have their own issues.

10. We recommend a blog as a central way to communicate to those who want to know what is going on. Ours has been an incredible blessing to us and our loved ones both. If you don't want a blog, you might look itno CaringBridge sites.

11. Go together to all of the doctor appointments. Two pairs of ears hear better than one pair.

12. Apply for FMLA at both jobs, so that you can go to doctor's appointments without risking your job in any way.

13. Resolve any non-mortgage debt you have as quickly as you can, so that you don't have any extra financial worries as you fight your illness.

14. Take the drugs if getting a bone marrow aspiration or biopsy. Tyler had 2 bone marrow aspirations before he started getting conscious sedation and he still remembers how much they can hurt.

15. Have hope that your treatment will work. Oftentimes our minds can will our bodies to work or not, based on our mood.

16. Cry over the disappointments for a day and then get up and fight again.

17. Live every moment and celebrate every day together!


We know that many others have faced similar challenges and welcome you to add your own comments about your first steps for dealing with a diagnosis like this.

A Good Week, but now some concerns...

We had a very good honeymoon and will fill you in more on that front in a later message, but for now I thought it more important to get the news out about Tyler's health. On Monday, December 17th, we had an appointment with Dr. M to get the results of the Bone Marrow extraction from the 12/4 and the Gleevec level test that Novartis (the manufacturer) was offering from Dec 7th.

After being off Gleevec for a full week, we were hoping that Tyler's platelet count had climbed back up into a more comfortable range. Unfortunately, Monday's test showed that he had actually dropped to 21 for his platelets and his White Blood Cell count had climbed to 52000. This is a bad sign and, an in combination with the Gleevec Level in his blood, indicates that his disease is no longer responding to his chemotherapy drug.

The doctor also discovered that Tyler had a temperature of 101-102 and an ear infection and recommended that he check into the hospital that night to get both of those things under control with intravenous antibiotics.

He is switching Tyler's medicine to Sprycel (the next generation of drug after Gleevec) as soon as the hospital pharmacy can get some and we'll hope for a positive response to that. They do say that Tyler will most likely need a transplant now to fight his disease. We hope to learn more over the next few days.

He doesn't feel really sick, so he is resting fairly comfortably in a private room. I think his biggest challenge will be boredom, so I'm taking a stack of movies to him tonight. Frequent score updates will be helpful for any NFL games being played this week (although I'm hoping he will be out in time to watch them).

Thank you for the prayers being said on his behalf and for the calls and e-mails sharing love and support. He is currently at Steven's Hospital, in Edmonds, in Room 802 if you want to call or come by. Visiting hours are 2pm - 7pm and we expect to be at the hospital for a few days this week, if you decide you want to visit.

Thanks!

Mandy

Wow! We've had more than our share of trials recently. It all began on Halloween (Tyler's birthday) and we've been battling different issues since then.

Probably one of the most challenging is the fact that our mini has been totaled (from a minor collision) due to some damage of the engine block. Tyler was hit by a lady entering a road from a parking lot on Halloween evening. He was completely stopped and she just never saw him there. He's been fighting with the insurance company this week to get fair compensation from them for our vehicle.

So... We are in the market for a vehicle. Ideally, it will be something that is reliable and handles well in the snow. Other than that, we are somewhat flexible.

The other challenge that we are currently facing is a slight blip in Tyler's health. We went in to Dr. M's office on Tuesday for a bone marrow aspiration. This was pretty much a 3 month follow up from his last bone marrow test to see how his body has been responding to the Gleevec. His blood test that day revealed a low platelet count, which is one of the danger signs for Ty. He's been hovering in the upper 100's (175-190 range) for several months, but this test showed him down at 106. The normal range is 150-400 for platelets.

I asked the doctor if we needed to be worried about anything for our upcoming trip and he immediately got worried. We have decided that the mere thought of a week away with me stresses Tyler out completely, so his body's response is just his way of trying to avoid a honeymoon.**

Thankfully the doctor got the hint that we were going on our honeymoon regardless and came up with some alternate strategies. Tyler went in for another blood test this morning to see if Tuesday's test was in error. Unfortunately, today's test showed that his platelets dropped down to 86 and his white blood cell count had climbed from 7400 to 12400. Target range for his white blood cells is 4800-10800.

The doctor has taken him off Gleevec for the duration of our trip, but we DO get to head out of town. We could use some prayers that his platelet count climbs back up and he responds well to the Gleevec when he goes back on next week. We don't tell you this to worry you while we are out of town and unavailable; just a message to keep all of you up to date on our crazy life.

On the upside, we are flying to Miami TOMORROW to begin our long awaited honeymoon. We'll be cruising on the Carnival Valor to Belize, Cozumel, Grand Cayman Island, and Honduras. It's going to be so very great for us to get away and spend some quality time together over the next week. We'll take a bunch of pictures of the beautiful places we see and share some of them online when we return.

Much love to you!

Mandy

**Tyler's theory is that the stress of talking to Farmer's Insurance Agents has caused the unusual spike in his WBC and drop in platelets. Also, the bone marrow extraction involves a needle penetrating his sternum, so he thinks that wound may cause some of the white blood cell spikes.

So.. We've had some blog confusion on our end. Tyler wrote up a great (I assume) post about getting the test results, but it didn't get posted for all to read. Sorry for making you wait. Thankfully, my sister called and reminded me that I was letting you all down. I guess Tyler and I need to come up with something more interesting to talk about, so we aren't always waiting for doctor's visits or test results. Perhaps we could post our fantasy results each week! ;)

Anyways, the doctor's visit for the bone marrow results went okay. Dr M said that Ty is down to only 1 in 50 cells with the Philadelphia chromosome, which is a great improvement.

On the down side, the doctor was disappointed in those results. He was hoping we would be at complete remission by this point. He gave Tyler the option of increasing his daily dosage to 800mg of Gleevec or continuing at 600mg and retresting again in a few months. The standard dosage is actually 400mg, but our doctor said that patients who are able to tolerate a 600mg dosage achieve better long term results, so he started Tyler off there. Ty has handled that dosage with only a few symptoms, so it was a good decision.

There is concern, however, that if we increase is dosage to 800mg, that he might experience more side effects from the drug. Tyler opted to stay with the 600mg dosage, to make sure that he is able to continue working full time unhampered by side effects.

I think we were both a little unsettled after the doctor's appointment, but pleased that Tyler seems to be making progress still. Our next visit is right before our vacation to Mexico, so hopefully he gets good results from that. I'll be surprised if the doctor continues to see us every month. The recent blood tests have been pretty steady, so unless they are using the more sensitive tests each month, there wouldn't be too much to test on.

Thanks for your continued support, the prayers, and the friendship!

Mandy

New Drugs on the Horizon

More about Gleevec
This comes from a mailing list I belong to, but is interesting in terms of the drugs to watch for over the next decade:
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It's hard to believe how far we've come in CML treatment in just 10 years. To think that 10 years ago, we had little to hope for other than the horrors of Interferon but now the number of drugs that are being developed to treat CML is at a point where it's actually hard to keep up with all the information.

In case any of you are interested in learning more about the drugs that are being investigated. Here is a list of a few that I was able to find.

1) Sprycel. This drug is now approved in many countries and is also known as Dasatinib or "the BMS drug". It's a dual bcr-abl and Src inhibitor and many of our list members are already taking it.

2) Tasigna. This is widely available in trials around the world and is also known as AMN 107 or Nilotinib. It's a bcr-abl inhibitor much like Gleevec but more potent and again, a number of our list members are already taking it.

3) Bosutinib. This is another drug that is being used in trials around the world and is also known as SKI 606. It's a dual bcr-abl and src inhibitor.

4) INNO-406. This is a Bcr-Abl and Lyn-kinase inhibitor that is available at some of the bigger trial centers.

5) MK-0457. This is a drug that is being used to treat people with the dreaded T315I mutation. It's an aurora kinase inhibitor.

6) Homoharringtonine or HHT is actually an older drug that is also being used in various trials for the T315I mutation.

7) KW-2449 is an aurora kinase inhibitor that I don't know much about other than it's being trialed in a few of the bigger centers.

8) Lonafarnib is a farnesyl transferase inhibitor being used in some trial centers.

9) GX15-07MS is a drug that is being used in some centers for blast phase CML.

10) ON012380 is a drug that is supposed to be 10 times more potent than Gleevec and is being trialled in some Gleevec resistant patients.

I'm sure there are even more drugs out there in the pipe line that I've forgotten to mention but as you can see, we're living in very exciting times.

Here's a great website that lists some of the drug trials that are being done at MD Anderson if anyone wants to check them out further: http://tinyurl.com/2pnprg

And this site gives a brief summary of the Abl and Src inhibitors. http://www.medscape.com/viewarticle/559294_8

It's been a rough week for both of us. I woke up with a bad cold last Wednesday. I was feeling bad enough that I actually left work early and went home and climbed into bed. Tyler caught my cold (I think) by Saturday and just got worse and worse. It was reminiscent of the pneumonia he had just before the wedding. Tyler spent most of Sunday and Monday sleeping, which is very unlike him. He was also running a fever, so we called Dr. M's office on Monday morning and Tyler got a prescription for antibiotics.

On the third day of antibiotics he was feeling well enough to go back to work. When I checked with him this morning, he said he was better today. He still sounds congested, so that I don't recognize his voice on the phone, but he isn't coughing quite as much anymore.

It does make us a little bit nervous. We don't really know what medications he can take while on Gleevec, so it is tough to give him relief from his symptoms. They approved Tylenol for aches and pains, but we'll have to keep researching to find out what else he can take.

Tyler now promises to stay far away from me the next time I sick. I don't think he wants to go through this again. I guess that means I will have to take extra care with my health now too, so that I don't put either one of us at increased risk.

On a much more positive front, our friends Mark and Vicki just gave birth to their first child. We would like to officially welcome Collin to the world and we're hoping to be able to meet him in person soon.

That's the latest from our house...

Mandy

We had another appointment with Dr. McGee on Tuesday this week and are pleased to say that Tyler's blood counts are still in the normal range. In fact, the doctor is so pleased with Tyler's progress that we don't have a blood draw or doctor's appointment for a month. While we enjoy all of the wonderful people at our doctor's office, it is nice to be free of the commitment to stop in there every two weeks.

One thing that I found particularly interesting at this visit was Dr. McGee's discussion of the Generation 2 and 3 drugs for CML. While Tyler is responding very well to Gleevec, the drug companies are racing to come out with better and better drugs for this disease. They are currently running clinical trials on the Generation 2 drugs and finding that they work well for folks who were not responsive to Gleevec. As time goes by, we may see patients who have been responsive to Gleevec switching to the newer drugs. While the doctor didn't give us a specific time frame for when he might be making a decision for Tyler to make the switch, he seemed to indicate that it was indeed something we might expect in the next few years. It's hard for me to believe that another drug would be even better for Tyler. He's responded so well to this one and has had so few side effects, that I am hard pressed to imagine a less invasive drug.

On another note, we are thinking about starting a team for Light the Night -- a fundraiser for the Leukemia and Lymphoma society. Anyone can participate in the walk or by offering donations. If you don't receive an invitation in the next few weeks and are interested in participating or contributing, please contact either one of us.

I think we'll be participating in the Greenlake walk on September 15th, but Washington has walks organized in Tulalip (Sept 15), Olympia (Oct 6), and Tacoma (Oct 6). If you live in another state and want to walk, we can look up a walk in your area for you to join and still have you on our team! The walks start at 7pm, with registration an hour before that. The course is about 2.5-3 miles on a flat stretch, so you can be at any fitness level and still participate. Keep your eyes out for more information!

If you already know that you want to participate, please feel free to post a comment on the blog. It'll be fun for us to see that someone actually reads this!!

Thanks,

Mandy

Hello everyone, it is now June and things keep getting better every day! Earlier this week I had an ultrasound on my spleen to see if it had returned to its normal size. I received a call from the doctor yesterday and was told it had indeed returned to normal. This means that I can be active without worrying about damaging/puncturing my spleen.

I was able to join the soccer team last night for the first time since last november for outdoor soccer. It was such a great feeling to be out on the field again! I was able to play most of the game without getting too tired, but had to take several water breaks.

Work is also much better for me as my energy has increased steadily, and I feel I am getting close to 100% again. The chemotherapy medicine they are treating me with has been so amazing for me. Not only is it searching out and destroying the mechanism in my body that creates the "bad" white blood cells, but I feel better than I have in probably two years! I have minimal side effects with this medicine also, which is lucky because many people do have problems with side effects including nausea.

I have so many things to be thankful for, including all of you that have prayed for me, thought about me, and helped me get through this initial part of my battle with this cancer. I am so thankful to have Mandy in my life as she keeps me grounded and always looking forward to each day!

Take care,

Tyler

Entry for April 19

Today it has been exactly two months since I was diagnosed with CML. It seems much longer than that, because life seems so normal right now. I had expected it would have taken much longer to feel as well as I do now. The Gleevec is an amazing drug, and it brings me much hope that I will fully recover.

I have been extremely blessed to have Mandy by my side, as she has provided me with her energy and spirit! The only times I feel sad right now is when she goes off to play soccer. I really miss playing soccer, and being with our friends on the field.

My blood counts have been in the normal ranges mostly the last three times. I need to show normal ranges for a couple more weeks before Dr. McGee can scan my spleen and maybe give me the okay to play soccer again.

In the meantime, I really need to get some inspiration to hit the track, stationary bike, and swimming pool as we will be entering a mini-triathlon in June. (3mile run, 1/4 mile swim, and 12 mile bike ride)

Thank you all so much for your caring and prayers. I can feel them with me!

Tyler

Entry for April 12

T's tests yesterday showed that he is back in normal ranges for almost all of his blood counts. His platelets had climbed another 100 to 287, even though he started taking the Gleevec again over the weekend. Dr. McGee upped T's Gleevec dosage from 400mg per day to 600mg per day. Hopefully the blood counts will stay in normal ranges over the next several tests.

T has blood draws only for the next 2 weeks and then an appointment in the 3rd week. We're hoping for good news in all of the appointments! Overall, he seems to be feeling good. His job is tough now, but he seems to have the energy to keep up, so that is a good thing. We'll see how his energy level is after a full month of hard work and expected overtime.

Thanks to all for the prayers and well wishes. We sincerely appreciate every ounce of support from each of you!

On the newlywed front, things are GREAT! We are enjoying each other's company as much as ever. I'm so thankful that I waited for this wonderful man! We are still trying to finish up thank you notes, so if you haven't gotten one yet it is only because I ran out of cards with appropriate themes. I really wanted to share a wedding photo on the cards because I had liked that so much with my sisters' weddings. But it took us a long time to get pictures due to some challenges in our photographers' lives. We have gotten the pictures now and hope to finish up on making the next batch of cards. If you have known me long, you know that I'm a procrastinator so you probably aren't too surprised.

I guess that is all for today's note; I just wanted to share the latest results with you.

April 9th Post

Ty's latest test results showed that his platelet counts were back up into normal range. The doctor has authorized him to resume taking Gleevec, although he is only supposed to take a 400mg dose and not the 600mg dose he was taking before his sinus infection kicked in. He wasn't experiencing any side effects, other than the anemia and low platelet count, so I am hoping they will be able to up his dosage again soon. The 600mg dose is supposed to provide better results for those who are able to manage it.