GIST Support WikiThis page is for information related to Bevacizumab (Avastin) and Sutent, one of the combination trials under Clinical Trial Drugs. Feel free to add your own experiences with the trial in the comments section or any other links to useful resources.
[edit] Basic Information
Manufacturer: Bevacizumab (Avastin) is manufactured by Genentech. Sunitinib (Sutent) is manufactured by Pfizer.
Molecular Targets: Bevacizumab targets VEGF, the angiogenesis growth factor
Trial: Phase I trial of this drug combination is underway - follow this link
GIST Support International website page: link here
[edit] Comments from Trial Participants
Kevin - 27th April 2008 (original attempt at posting in the beginning of March, but that one was lost - let's hope this one gets saved properly).
As far as i know, i'm the first person to try the combination of Sutent and Avastin with GIST (no GIST patients are registered with the trial in Cleveland). I thought i would share my results and experiences with you cus it might be helpful to others here.
A bit of background info on my case: First i live in Sweden - so i have full medical coverage in a technically advanced medical system, but not always the best doctors (although my current onc is good, and there are a lot of good nurses). I was diagnosed with GIST (8.5 cm tumor in the stomach) on July 21st 2005 (and it only took 6 months and 6 doctors to find it!). A DNA analysis (which i had to send off for analysis myself) showed an exon 11 deletion mutation. Mid August i started on Gleevec at 400mg (my own initiative - not the doctors). 13 months later it was upped to 800mg when the latest scan showed rapid growth (800mg made no significant difference). Surgery on November 29th 2006 to remove a 21 cm tumor as well as my entire stomach (but since they ruptured the tumor and didn't get clean margins they spread the problem significantly). DNA analysis (my initiative again) of the tumor section i sent off showed a secondary mutation at T607I. Back on Gleevec in June 2007 after several new tumors developed (this was my mistake - i should have started Gleevec directly after surgery). Failed in early October 2007 after tumor growth had cut off my ability to swallow. Started on 37.5mg of Sutent which fortunately was able to shrink the large tumor blocking my intestines. Unfortunately, a PET/CT scan one month later showed that 5 of my 8 tumors were still growing rapidly.
Sutent + Avastin: At this point (early November 2007) i convinced my doctor to try adding Avastin (5mcg per kilo body weight given intravenously every 3rd week) to my treatment with Sutent. Avastin and Sutent both include VEGF inhibitors, but they work in different ways. In theory, they could compliment each other and make a good combination. The next scan i had (in the middle of December) gave somewhat positive results. There was still activity in the tumors, but they hadn't increased significantly in size. The most recent scan (at the beginning of march) wasn't as positive. Some tumors had shrunk, but several were agressively growing, including 4 new ones (making 12 all total) that hadn't appeared on my scan before. Oh well, i did get 5 extra months from these medicines, so that's good. What wasn't so great were all the side effects.
Sutent + Avastin Side Effects: The combination of Sutent + Avastin may be useful for anyone with multiple mutations, but do be aware that the side effects are quite extensive. Here are the one's i had as well as the ways i found for dealing with them.
- Feet - Ouch! Very painful when walking. The soles of your feet become very sensitive. It turns out the worst of it is caused by these hard multi sided sharp white sand like buildups underneath your callous. I found that by soaking my feet in warm water a really long time i could use my thumb nail to scrape off the areas and the sharp stones would come out. At first i dug them out with a sharp sterilized blade on dry feet, but the soaking trick worked a lot better. Various skin/hand creams helped with the sensitive skin in general (got the best effect by switching them around). What didn't work was Biafine emulsion. Neither did a menthol based emulsion.
- Skin - very sensitive. Hot water, pressure (like playing guitar or walking), scratching - all these became quite painful at times. It was worst with my hands and feet, but pretty much everything was effected.
- Mouth - very sensitive. Forget spicy foods, garlic, onions, mint, and adult tooth pastes - they all had to be cut out. I ended up using 3 different children tooth pastes (Tom's Silly Strawberry, Aim Holly Hobbie, and something here in Sweden by Pepsodent), but none of them did a very good job of cleaning my teeth.
- Splitting at the edge of my mouth. Used ChapStick and a couple of other lip balms, but it only alleviated the worst of it, it didn't eliminate the splitting.
- Mouth - dry and swollen. Never found anything for this.
- Bloody Nose. Happened all the time, especially in the morning.
- Strange sinus pressure headaches.
- Stuffy in the head. Kind of like when you have a cold, but without the runny nose.
- Itchy. Sometimes this drove me nuts, especially on the legs. No amount of scratching helped (it often made it worse). Hand creams helped somewhat. Locoid didn't help at all.
- Weak. My muscular strength seemed to be seriously affected. Not sure why.
- Fatigue. Was tired most of the time.
- Extra sleep - up to 12 hours a night. I would sleep 30+ hours after each infusion of Avastin (once every 3 weeks).
- Diarrhea. It was really bad. I was on the toilet 7 or 8 times a day. Used Imodium but it only helped somewhat and it would cause intestinal cramping if i used it too many days in a row.
- Burning butt syndrome. Seriously burned whenever i shit. It was really painful, especially after i developed cracks in my anal area. Applying a creme with 5% Urea after each toilet round helped somewhat.
- Yellow urine. Actually, it was almost orange. Just so you know, it causes permanent stains.
- Watery sperm. Actually, it was like there wasn't any sperm at all in the semen.
- Sore teeth and gums. Felt like my teeth were coming loose.
- Dry nose. So dry it was painful, especially after sleeping. Water was all that seemed to help.
- Changed taste. Salt tasted worse, but sweet things actually tasted better. Got a serious sweet tooth cus that was what tasted best.
- Sweaty hands and feet - constantly. The sweating even left a tacky residue after itself. I had to clean my computer mouse and keyboard several times. Except for when exercising i never sweated in my hands and feet before.
- Lost voice. I had little or no voice for 80 - 90% of the time i was on Sutent + Avastin. I found i was good for an hour or so a day of talking. Any more than that required one of more days of silence to recover.
- Occasional cramps of hands and feet. Kind of like when you are on Gleevec, only these were pretty mild and only lasted a few seconds - not like the several minute long cramps your entire leg or back nightmares i got several times a day on Gleevec (eliminating Pectin and Raspberries from my diet radically reduced this Gleevec related problem).
- Rashes. Got these red blotchy type of rashes in places where my clothes rubbed on me or anyplace i would scratch. Hand cremes helped a little.
- Red skin. Whenever i did any kind of strenuous activity (which was very mild in comparison to my pre-treatment days) i would turn all red in my skin. Think tomato.
- White hair - all hair. Gives you some idea of how you might look if you manage to live a decade or two longer.
- Reduced creativity and inspiration. Doing practical work was fine, but stuff requiring creativity and inspiration was detrimentally affected. Not too great if you are a musician.
Ok, so that's the list. Enough to scare anyone considering trying this! Yeah, it was brutal, but i never felt like it was more than i could bear. All in all i felt handicapped, but not incapacitated.
Next step - Tasigna and beyond: First off, i think that a cocktail approach is the most promising (and brutal) in controlling advanced GIST, but as that is totally experimental at this stage choosing drug combinations is a difficult dilemma. So, at the moment i'm running a quick rotation game. That is, keep rotating TMDs that provide partial mutation blocking in hopes that nothing gets too big and kills you. I'm currently on Tasigna in hopes of blocking the exon 11 deletion mutation (and maybe a few others) in some of the most aggressively growing tumors (and mine are really really aggressive - even when i was on 800mg of Gleevec it was 44 mitoses/50Hpf). However, it's only temporary since Tasigna won't block the T607I mutation (too bad cus the side effects of Tasigna are minimal). Gonna see if i can convince my doctor to add Sutent cus Sutent would block T607I and hopefully the combination will block whatever other mutations i currently have (since i had zero wash out when switching from Sutent + Avastin to Tasigna i already have a pretty good idea of what i'll be facing in terms of side effects). If i can't do that then the next step is Nexavar (Sorafenib) which has shown some effect when people fail both Gleevec and Sutent. Would have liked to be on XL820 (which blocks 28 of the 29 identified GIST mutations) but i don't qualify for the trial (if you've tried anything other than Gleevec or Sutent they won't take you). If all these fail then it might be PTK787 (which so far has had a 70% success rate with Gleevec resistant tumors). I'm currently saving the HSP90 drug IPI504 (perhaps in combination with something else) as the last line of defense. Obviously, as other drugs emerge (and they are doing so very rapidly) then these plans will change. The trick is to stay alive long enough to keep ahead of the curve.
28 Jan 2008
Has Kevin told you that he is taking Avistan along with the Sutent and that it had an amazing and immediate positive effect? In mid November I thought from his condition just before he started the Avistan that death was very very close. Three days later he was a different person and all the fluid in his abdomen was gone as well. His weight has been a problem though because of the diarrhea associated with the drugs and his life long need for huge amounts of food to maintain his strength and weight. Consequently, he has really wasted away due to lack of adequate nutrition, although he says that he has gained a couple of pounds in the last week or so, thank goodness, because he has begun cooking again. Anyway, the tremendous positive response to Avistan combined with drugs being used for so many kinds of cancer makes me wonder why Kevin seems to be the only person with GIST who is receiving it. He is also not taking any breaks from the Sutent. I don't know how long this combination will continue to be effective, but the Sutent stopped working after only about 5 days and Kev went down hill very fast until he started the Avistan which he had to research and convince his reluctant onc. to try. What a shame all GIST patients and their doctors don't know about this wonder drug.
Thank you for all the information that you have provided to Kevin and so many other grateful, frightened, searching people. You are a real blessing!
Sincerely, Janie Flatt (Kevin's mom)