https://www.youtube.com/watch?v=sq8Hmv81yBs&feature=youtube_gdata_player
Tuesday, February 25, 2014
Monday, February 24, 2014
Brody is Home
Brody finally got to come home from the hospital today after a very long and rough week. He is feeling at least 10,000 times better than he did a week ago and is very happy to be home. I think he missed his dogs (Chewy and Tori) the most. He was telling us about several dreams he had about Chewy and Tori last night and hugging them was the first thing he wanted to do when he got home.
Jaden, myself and our friends Carolynn and Mirissa Corthell worked on a special surprise for Brody last night. Brody is a big Minecraft fan and has been asking for a "Minecraft room" the last couple of months. We all worked late last night to give him a Minecraft room as a surprise welcome home gift. Our friend, Michelle Roush, brought by a green and black balloon bouquet for his Minecraft room this morning. Jaden couldn't wait to show Brody the surprise. Brody was tired when he got home and enjoying the dogs so we had to have Jaden wait a bit to show him. Jaden finally convinced him that there was something really awesome he needed to show him upstairs. Brody can't walk very well right now and didn't want our help getting upstairs to checkout what had Jaden so excited, so he decided to crawl up the stairs. Jaden was so proud to show his brother the surprise and happy to see how much Brody liked it. I took a video of Brody seeing his new room. I will try to post it later.
Brody is feeling better but does still have several frustrating and difficult things to be dealing with right now. His groin is still very swollen and painful. He has leg pain, weakness in his legs, and belly pains that come and go. (belly pains are much less frequent and severe though). He gets tired and short of breath easily. He has regained control of his bladder and bowel function again. We are so thankful for this and that he is not in so much pain.
Brody will continue with radiation treatments Monday through Friday for the next few weeks and will be at Toledo Hospital for labs, check-ups, and blood, and platelets as needed on Mondays, Wednesdays, and Fridays. Every 3 weeks, he will repeat the days of chemo he just finished. Now that Brody's colon is no longer distended, he will also be getting the bevacizumab every other week too.
We are all so happy to be home again with Brody and to see him happy and acting like himself again. It has been a tough week and we are glad to be through it. It would've been much more difficult if not for the help of so many. Thank you to all of our friends and family that have helped us in so many ways this week. I don't know what would do without this support.
Friday, February 21, 2014
Brody Had Another Good Night and is Showing Signs of Improvement
Brody did not complain of any belly pains last night. He ate some peaches and popcorn and drank some chocolate milk while watching Brer Rabbit. He was enjoying his popcorn a little too much for my comfort level though. I had to make him stop eating it. I was afraid he was going to make himself sick eating too much of it at once. He was NOT happy about that. He would've eaten the entire bag if I had let him. Also, before going to sleep his belly was huge (it looked even more distended and as though that situation was getting worse). I was very worried when going to bed that he was going to be miserable after attempting to eat and that the distention would get worse rather than better. But, quite the opposite started happening. Each time I had to wake up Brody to have him pee, his belly appeared and felt to be getting less bloated and distended. Also, each time I woke him up when I checked his pull-ups there was no stool in them. For the past several days he has had NO control of bowel fuction and his pull-ups would always have leaked stool in them. Not last night though and so far not this morning either. And, he had to wake me to tell me he had to go poop! I helped him to the potty and he was able to hold it until he got on the potty!
I went to sleep last night so worried and with virtually no hope left and this morning I see the light of a little sliver of hope. Hope keeps you going; without it, I don't know how to get through.
Thursday, February 20, 2014
Started Radiation Therapy
Brody had a "relatively" good day compared to earlier in the week. His belly is still distended but his pain was well managed today. He has not gotten any Morphine since last night and has been taking the oral bentyl capsules that ease up his "gut cramps" so while he does have occasional belly pain, it isn't for too long or too severe..
He was supposed to get blood today due to low hemoglobin yesterday, but his hemoglobin came up some so they didn't have to give it. His color and dimeanor was much improved today too.
He played games with Jaden and got his chemo and watched "The Tooth Fairy". Then he was taken over to Flower Hospital and did his radiation therapy. The session lasted about 20 to 30 minutes and according to the nurses/technicians, he did great-- he has to lay perfectly still in a body mold they made earlier in the week-- they use lasers shining on his body (the tatoo marks they made on tuesday) to align the machine with his body so they can precisely aim the radiation at the tumor in his spinal column-- the radiation part lasts about 15 to 20 minutes-- 14 more sessions to go (they operate monday through friday)so he will be done in 3 weeks-- his appointments are all in the afternoon vs when he was 4 years old and they made him go at 7:15 in the morning.
When we go back over to Toldeo Hospital, Brody watched Monsters University and finally ate a little bit of food... he hasn't had anything to eat that he could keep down since Sunday, he has been drinking chocolate milk occassionally. He did eat a gummi "car" yesterday-- today he ate a couple pieces of canned sliced peaches and 4 peanut butter crackers out of a vending machine (that is what he wanted) and has so far tolerated them well... he just sent Trish out to get him some "movie" popcorn.
As mentioned previously-- is biggest issue is bowel control and also he doesn't really notice when his pull up has stool in it either so he has been going through alot of pull ups-- hoping the radiation therapy starts helping with this soon. Kid has amazingly tolerated this-- we explained to him why this is happening that it is not at all his fault-- he isn't crazy about mom and dad cleaning him up but he has suffered from "raw butt" before and knows that is a lot worse--
We finally got our "Hamster" problem taken care of-- there are 4 more hamsters that need to be adopted but one of the parents in our boys cub scout troop has taken them and said we have enough to deal with now and she will find homes for them (there were 7 needing homes but she found homes for 3 of them already).
Another issue right now is Geordi- he woke up with a sore throat this morning. I checked his temperature this morning and it was ok-- I gave him some motrin and grape juice and he said it felt better before he got on the school bus.... we got a call from the school nurse today that he had a fever..... took him to the doctor and he tested positve for Strep... so he is on antibiotics and is going home with Trish's dad tomorrow. Hopefully he will recover quickly.
Thats about all I can think of now-- thanks for all the words and prayers-- (most of these we get on facebook nowadays)....
Bill
He was supposed to get blood today due to low hemoglobin yesterday, but his hemoglobin came up some so they didn't have to give it. His color and dimeanor was much improved today too.
He played games with Jaden and got his chemo and watched "The Tooth Fairy". Then he was taken over to Flower Hospital and did his radiation therapy. The session lasted about 20 to 30 minutes and according to the nurses/technicians, he did great-- he has to lay perfectly still in a body mold they made earlier in the week-- they use lasers shining on his body (the tatoo marks they made on tuesday) to align the machine with his body so they can precisely aim the radiation at the tumor in his spinal column-- the radiation part lasts about 15 to 20 minutes-- 14 more sessions to go (they operate monday through friday)so he will be done in 3 weeks-- his appointments are all in the afternoon vs when he was 4 years old and they made him go at 7:15 in the morning.
When we go back over to Toldeo Hospital, Brody watched Monsters University and finally ate a little bit of food... he hasn't had anything to eat that he could keep down since Sunday, he has been drinking chocolate milk occassionally. He did eat a gummi "car" yesterday-- today he ate a couple pieces of canned sliced peaches and 4 peanut butter crackers out of a vending machine (that is what he wanted) and has so far tolerated them well... he just sent Trish out to get him some "movie" popcorn.
As mentioned previously-- is biggest issue is bowel control and also he doesn't really notice when his pull up has stool in it either so he has been going through alot of pull ups-- hoping the radiation therapy starts helping with this soon. Kid has amazingly tolerated this-- we explained to him why this is happening that it is not at all his fault-- he isn't crazy about mom and dad cleaning him up but he has suffered from "raw butt" before and knows that is a lot worse--
We finally got our "Hamster" problem taken care of-- there are 4 more hamsters that need to be adopted but one of the parents in our boys cub scout troop has taken them and said we have enough to deal with now and she will find homes for them (there were 7 needing homes but she found homes for 3 of them already).
Another issue right now is Geordi- he woke up with a sore throat this morning. I checked his temperature this morning and it was ok-- I gave him some motrin and grape juice and he said it felt better before he got on the school bus.... we got a call from the school nurse today that he had a fever..... took him to the doctor and he tested positve for Strep... so he is on antibiotics and is going home with Trish's dad tomorrow. Hopefully he will recover quickly.
Thats about all I can think of now-- thanks for all the words and prayers-- (most of these we get on facebook nowadays)....
Bill
Brody had another good night
Brody did well again last night. His belly pain was not too bad and he slept well except for Mom having to wake him up and make him pee every couple of hours. He still can't empty his bladder fully and does not get a sensation that his bladder is full and he needs to pee. So, we gotta have him go every couple hours to keep him from becoming fluid overloaded. He also does not have control of bowel fuction right now either. Each time we have him go pee, his diaper is usually full of very loose stools. So each time we have to wake him up to go pee it's also a cleaning him up process too. It is hard for him to get any solid sleep through all of this obviously. So far, knock on wood, his bottom has not gotten very sore. We are coating his bottom very heavily with bag balm to keep his skin protected.
Brody remains in good spirits through all of this. It's amazing how much he tolerates and yet still he is a basically very happy child. He is a very tired boy too right now and is sleeping most of the day and night. When he does wake up though, he usually has a smile on his face.
He was glad to spend some awake time with his Papaw and brother Jaden yesterday. They watched Cars 2 together until Brody fell back asleep. Brody was asking in the middle of the night if Papaw got to watch the whole movie and wanted to know if he liked it. He says, "Papaw likes cars, trucks, and tractors, I bet he liked it." Papaw will have to let him know today what he thought of the movie.
My dad has been helping us out this week with watching Geordi and Jaden. He has them busy keeping up with chores at home for us too. He has them doing laundry, vacuuming, cleaning bathrooms, cooking, and cleaning the kitchen. They are taking care of all our numerous pets and of course doing their school work. Geordi and Jaden are being very big helpers this week and my dad is helping them realize how many little things they can do around the house that add up to be very helpful for the whole family. My boys are growing up so fast.
Wednesday, February 19, 2014
Brody's Surgery Went Well Today and He is Feeling Okay
Brody's surgery went well this morning and he has felt pretty good most of the day.
He started chemo today and is handling it good so far.
Brody's hemoglobin is low already from the chemo he had last week. So he will be getting blood tomorrow.
Brody will start radiation treatments to spinal column tomorrow and continue on with chemo for next 4 days.
Brody has been able to eat small amounts of solid food today and has been drinking some chocolate milk.
Tuesday, February 18, 2014
Slight Change of Plans
It has been decided to not use bevacizumab along with the cyclophosphamide and topetecan due to fear of bowel perforation. Brody's colon is majorly distended and stretched thin. The risk is too great to use the bevacizumab.
Brody Continues to Feel Better than Yesterday
Brody continues to feel much better today than he did yesterday. He has been sleeping most of the day as his medications to keep him comfortable also make him very sleepy. He is still having some belly pains but they are not as severe nor nearly as frequent either.
Brody had scans done this morning as part of his radiation planning session. These scans showed that his tumor has "obviously gotten bigger." And, it is obstructing parts of his GI tract. It has encircled the rectum. His large intestine (colon) and rectum are especially distended.
Brody will be starting a new chemo regimen today. He will be in the hospital for at least the next 5 days as he starts this. He will be taking Topotecan, Cyclophosphamide, and Bevacizumab. He will get the Topetecan and Cyclophosphamide each day for 5 days. He would get this days 1 through 5 of a 21 day cycle. The Bevacizumab would then be given also every other week.
Brody will continue to receive anti-nausea and pain medications to keep him as comfortable as possible. He also is still receiving Decadron to reduce the inflammation in the colon and in spinal column area.
It is hoped these changes will help take the pressure off his colon and rectum and make him feel much better.
He will be starting radiation treatments to his spinal column very soon too. Possibly looking at Thursday for this but do not know for sure yet.
He is still having biopsy surgery early tomorrow morning.
If these attempts to get the pressure off the colon and rectum do not work then we may soon be facing the decision as to whether to get a colostomy. At this point, surgery is not option to remove the tumor until we can find a chemo regimen that keeps the tumor from growing rapidly. Otherwise we will be right back to the same point we are right now rather quickly.
These have been some especially tough and very emotional days for me. Lots and lots of tears. I am at least managing not to cry in front of Brody though. I'll give myself a big pat on the back for that.
All of Brody's doctors and nurses have been wonderful and compassionate through this whole ordeal. We aren't the only ones shedding tears. So are they. Everybody is doing everything they can to help. It is so hard though that we all seem so powerless to stop this awful disease. CANCER SUCKS!!!!
Quick Update - Brody had a good night
Brody had a good night last night. The morphine, Bentyl, and nausea meds kept him comfortable. Thank goodness!!
He has the "sparkle" back in his eyes this morning too.
He was transferred from Toledo Children's Hospital this morning to Flower hospital so we can get the ball rolling with radiation treatments. These treatments will be at Flower. After we are done here Brody will head back to Toledo Children's Hospital.
Brody has surgery early tomorrow morning to get new biopsy of his tumor and healthy tissue biopsy too. These will be used for molecular profiling to help better guide chemotherapy moving forward. It may take up to 2 months for these results to come back though.
Monday, February 17, 2014
Brody is NOT Doing Well (Horrible Belly Pains)
Brody has endured more pain in the last 2 days than he has ever experienced. And, believe me, he has endured some serious pain. For the last 2 days he has not been able to eat or drink anything and has been having horrible and extreme belly pains. I took him into the hospital last night. They admitted him and started him on IV fluids and IV anti-nausea medicines. We could hear his belly gurgling and the pains were coming and going. So, we thought Brody was having problems with stool getting stuck/moving through his GI (gastrointestinal) tract and that his pains were from a stool obstruction. So we were very hesitant to give him morphine and other medications for the pain that could slow down the GI tract and make it even more difficult to resolve this situation. It has been awful watching him suffer so bad and not be able to do anything to help him feel better. He has had much shorter pains like this many, many times in the past and these would ultimately end when Brody finally had a significant bowel movement. Yesterday and today though the pains were far more frequent and intense and we were moving on to days of waiting for it to finally resolve with no luck. This evening Brody finally got an abdominal X-Ray to check for blocked stools. But, there was no signs of this. Instead, it looks like the tumor is causing a mechanical obstruction of his bowel.
Brody's tumor is blocking the normal peristalsis of Brody's GI tract. (Peristalsis in the gut or GI tract are series of wave-like muscle contractions that move food to different processing stations in the GI tract). The tumor is blocking the gut from being able to complete the "wave." This results in extreme pain each time the gut is blocked from completing it's series of wave-like muscle contractions.
Since we now know that he does not have impacted stool (blocked stool), we are now able to start giving Brody medication that slows down the GI tract and helps stop some of the muscle contractions in the gut. We are hoping starting these will help Brody feel much more comfortable. He just finally received morphine by IV and bentyl by IM injection this evening to help with all of the pain he has been endearing. Then, he is continuing to get zofran, benadryl, and lorazepam for the nausea.
I spent last night at the hospital with Brody and tonight Bill is staying with him. (One of us still needs to take Geordi and Jaden home in the evenings and then get them each ready for the next day....tonight I am wishing I would have asked a friend to help us out with Geordi and Jaden because I really would rather be at the hospital right now....tomorrow my dad is coming up to help out with Geordi and Jaden though....Bill and I should both be able to stay with Brody tomorrow night). Brody just got his first dose of IV morphine when I was leaving the hospital with Geordi and Jaden this evening. Bill texted that Brody was still having some belly pains when he was awakened. He got his first dose of Bentyl about an hour after I left and Bill said that Brody went back to sleep after this shot. Hopefully, he is able to stay asleep tonight and not be awakened all night by horrible belly pains. I am praying for a peaceful night for Brody (and, of couse, a miracle healing too).
Saturday, February 15, 2014
An Update
Brody has had a rough few days. He was admitted for chemo on Tuesday. He received the high dose IV cyclophosphamide, Mesna, Temsirolimus, and vinorelbine. He handled it all okay Tuesday night. He didn't have a lot of nausea and did not vomit Tuesday night. He was released on Wednesday morning in just enough time for us to travel to Flower hospital to meet with his radiation oncologist there. Brody had an MRI done on Monday of the spine. The radiation oncologist reviewed this latest MRI and let us know that radiation therapy to this region is certainly doable for Brody since his previous radiation treatments were not in this area and fortunately the area that needs treated now can withstand large doses of radiation. The risks and side effects sound fairly minimal for treating in this area too. (Certainly far less than previous treatments he went through). The MRI was also sent to Cincinnati Children's Hospital. The radiation oncologist and neurosurgeon there reviewed the MRI and concurred that radiation treaments ASAP would be the best next step for Brody. Brody has continued to have problems emptying his bladder and has been experiencing swelling again in his groin (especially after receiving cyclophosphamide). The swelling is fortunately, much better today compared to Wednesday and Thursday. Brody was very nauseated on Wednesday and Thursday. He had problems being able to eat anything without throwing up. He also started having a lot of pains in his left leg on Wednesday and Thursday. The nausea and the pains in his left leg were much better today though. He felt okay most of the day but did have periods of moderate belly pains off and on all day today. His leg was not hurting him today while sitting or resting but he was unable to walk on it.
Brody really wanted to go bowling this afternoon and to go see the Lego Movie. Neither of these excursions worked out today though. He kept having too much pain in his belly. Also, Brody didn't want to try bowling from his wheelchair. He cannot walk very well at all right now and would not have been able to bowl today without being in a wheelchair.
Brody's hair has started falling out again recently. He was getting upset today about how much and how quickly his hair was falling out. He was more annoyed with the pieces falling in his face and onto his tablet he was playing with than he was about actually losing his hair again. He finds the falling out process to be more annoying than just being bald again. We may be shaving his head for him again soon so he won't be so annoyed by it.
Brody is scheduled on Tuesday this next week for his radiation planning session. During this session they will make molds to hold Brody's body perfectly still for each of his upcoming radiation treatments. He will need to lie perfectly still for about 45 mins per session. They are planning to do 15 sessions. We are hoping that he will be able to start the actual radiation treatments very soon. We are not sure how long the delay will be between the planning session and the radiation treatments. We are hoping the radiation treatments will work quickly to shrink Brody's tumor out of the spinal column and that Brody will begin to feel much better. Many of his recent symptoms are believed to be due to the tumor in this location.
Brody will have surgery on Wednesday this next week to obtain biopsy samples. These will be sent to GeneKey in California. (please see previous posts about what GeneKey will do).
After the biopsy surgery, he will head up to the oncology wing for chemo again. He will not need to stay overnight for this one though. It will just be the temsirolimus and vinorelbine.
Brody has certainly felt better today than he did on Wednesday and Thursday. Let's hope tomorrow he will feel even better than today.
Sunday, February 9, 2014
Feeling much better
Just a quick update-- I (Bill) have been bad about posting in the Blog lately.
Brody has been feeling good since Friday evening. He was "tooting" a fair amount that afternoon so we are hoping his bellyache was from some extreme gas-- he ate a couple of skyline chili cheese coneys on thursday (2 at Cincinnati Childrens, and 2 more on way home) so we are hoping this was the source of his bellyache. Yesterday he felt good. He slept in as planned and he skipped his bowling league (I took Jaden-- Geordi was at a winter boyscout camp) and then yesterday afternoon we took Brody & Jaden to see "the nut job"which he liked a lot.
Last night we watched "The Blues Brothers" which he really likes. He gets a kick out of all the car crashes and likes the music for the most part.
His groin swelling has been well controlled so we have been easing up on waking him up at night to every 3 to 4 hours-- but during the day we try to make him pee every 30 minutes (set timers) so we don't get back to the point of him having to get up every 2 hours at night.
Overall he feels well most of the time and he has learned to adapt to what is his (our) new normal.
We got another few inches of snow last night and Brody expressed some interest in sledding yesterday on the way back from the movies (we drove past a nearby sledding hill) so if he is up to it we are going sledding in few hours.
Thanks again for everyones prayers, thoughts, & wishes.
Bill
Brody has been feeling good since Friday evening. He was "tooting" a fair amount that afternoon so we are hoping his bellyache was from some extreme gas-- he ate a couple of skyline chili cheese coneys on thursday (2 at Cincinnati Childrens, and 2 more on way home) so we are hoping this was the source of his bellyache. Yesterday he felt good. He slept in as planned and he skipped his bowling league (I took Jaden-- Geordi was at a winter boyscout camp) and then yesterday afternoon we took Brody & Jaden to see "the nut job"which he liked a lot.
Last night we watched "The Blues Brothers" which he really likes. He gets a kick out of all the car crashes and likes the music for the most part.
His groin swelling has been well controlled so we have been easing up on waking him up at night to every 3 to 4 hours-- but during the day we try to make him pee every 30 minutes (set timers) so we don't get back to the point of him having to get up every 2 hours at night.
Overall he feels well most of the time and he has learned to adapt to what is his (our) new normal.
We got another few inches of snow last night and Brody expressed some interest in sledding yesterday on the way back from the movies (we drove past a nearby sledding hill) so if he is up to it we are going sledding in few hours.
Thanks again for everyones prayers, thoughts, & wishes.
Bill
Saturday, February 8, 2014
An Update and What We Learned at Cincinnati Children's Hospital Thursday
Thursday, we met with a pediatric oncologist, radiation oncologist, and pediatric surgeon at Cincinnati Children's Hospital. We decided to consult with their team regarding how best to proceed regarding Brody's treatment. We chose Cincinnati Children's due to the larger number of clinical trial options available for recurrent rhabdomyosarcoma. They certainly seem to have a greater number of options for us than anywhere else right now. I have been very impressed indeed by the care and attention we received from Cincinnati Children's. It's a great hospital with an absolutely exceptional pediatric hematology/oncology team.
The tumor board at Cincinnati Children's Hospital reviewed Brody's case this week. The meetings we had Thursday were to discuss the group's findings and conclusions with myself, Bill, and Brody. My mom and dad traveled with us to the hospital Thursday and did a great job keeping Brody entertained and happy when the doctors were discussing items that may not be the best news for little Brody to hear at this point. I am quite glad my parents were able to do this for us. Some of the discussions we had to have were definitely not ones I wanted Brody to hear.
The oncologist at Cincinnati Children's Hospital told us several things we really did not want to hear. We learned that Brody's tumor has now infiltrated into the spinal column and there is a suspicious spot on his lung that may be tumor but they aren't sure yet. We were informed that the tumor board at Cincinnati Children's Hospital considers Brody's cancer to be incurable and that it is extremely unlikely that Brody will beat cancer. (This is not the first time we've been told this but it still hurts to hear it again). We were told that we had pretty much done every standard treatment for recurrent rhabdomyosarcoma and that his tumor has been exposed to a tremendous arsenal of chemotherapy agents but yet his tumor still continues to progress. He reassured us that Brody's treatment regimens have been absolutely appropriately chosen. He let us know that we have basically three options as far as chemotherapy at this point: 1) Phase 1 trials, 2) No further Chemotherapy (and possibly no further treatment other than comfort care, 3) Treatment not within a clinical trial. He assured us that any of these options would be appropriate for Brody and it's a very tough decision to make as to how to proceed at this point. He let us know that surgery and radiation treatments may still be an option for Brody too. But the important question is whether or not we should put Brody through another surgery and radiation treaments again. Will it provide him with any significant improvement in quality of life? It's hard to say this is something worth pursuing knowing that the tumor cannot be completely removed surgically and that it will certainly continue to grow and recur. It's more reasonable to consider if a chemotherapy option is found that significantly slows or stabilizes the disease and that we could expect a significant increase in the amount of time and quality of life for and with Brody. It was also discussed that radiation treatments could be done to the spinal column area to decrease the size of the tumor in that area to help improve Brody's symptoms. Fortunately, although Brody's tumor has entered the spinal column, it is not yet touching the spinal cord. Radiation treatments would not be possible around the spinal cord. We were surprised to learn that the radiation oncologist at Cincinnati Children's Hosptial still felt Brody could benefit from radiation treatments. When Brody's tumor recurred, it came back growing right in the pins that were used to mark where exactly to deliver his previous radiation treatments. The tumor was concentrated in an area that was known to have been hit very hard with radiation already. But we were told that sometimes, radiation treatments may still work anyway in cases like this. I guess we won't know until we try it. (Brody's radiation oncologist in Toledo did not feel that Brody's recurrent tumor would respond to further radiation treatments). We were also informed that if we decided surgical resection or debulking of as much as possible of Brody's tumor, that the radiation oncologist would have the surgeon place a "sleeve" to pull the bowel away from the area where the tumor is removed. He would want to do this so that radiation treatments could follow after Brody has healed from surgery to the area the tumor had been before surgery. The bowel cannot withstand very large doses of radiation and so if they can pull the bowel away from this area then they could provide higher amounts of radiation treatments.
The oncologist at Cincinnati Children's Hospital discussed each of the Phase 1 trials he felt would be most appropriate for us to consider for Brody. Two of them would be offered at Cincinnati Children's and one of them is offered in Columbus, Ohio at Nationwide Children's Hospital.
The first trial the oncologist told us about combines the novel drug, Crizotinib with conventional chemotherapy. The trial number is ADVL1212. He felt this trial may be of particular interest for us to consider because the conventional chemotherapy used in it is a combination Brody has not yet tried. The "conventional chemotherapy" in this trial is the combination of Topotecan and Cyclophosphamide. Brody has, however, taken Irrinotecan which is very similar to Topotecan. And, Brody has taken A LOT of Cyclophosphamide. Brody was not taking cyclophosphamide though while he was on irrinotecan. He was taking Vincristine and irrinotecan together. The tumor grew very quickly when he was on this combination. So, initially I was not very enthusiastic about this trial even though it did add a novel drug with some exciting potential for treating rhabdomyosarcoma into the mix of agents that Brody has been exposed to before or exposed to a very similar drug. Crizotinib is a medication that is one I have been certainly wanting to have Brody try but I was hesitant about the idea of the combination of Topetecan and Cyclophosphamide due to Brody's lack of response in the past to irrinotecan and that he has been taking cyclophosphamide for a long time and yet the tumor is growing. (I do think it would be growing a lot faster without the cyclophosphamide though). After giving it some more thought though, I do think this trial is one that is worthy of consideration for Brody. There have been cases of tumors responding to Topotecan that did not respond to Irrinotecan. In fact, there are trials that combine both of these drugs into the same regimen even though they are very similar medications since if a tumor is resistant to one it may not still be resistant to the other. So maybe Topotecan is worth a try. Crizotinib is a tyrosine kinase inhibitor, which inhibits anaplasitc lymphoma kinase (ALK), Hepatocyte Growth Factor Receptor (HGFR, C-MET), and Recepteur d'Origine Nantais (RON). ALK gene abnormalities due to mutations or translocations may result in expression of oncogenic fusion proteins (eg, ALK fusion protein) which alter signaling and expression and result in cellular proliferation and survival in tumors which express these proteins. ALK expression is found in 15-32% of embryonal rhabdomyosarcomas and 45-81% of alveolar rhabdomyosarcomas. (Brody has embryonal rhabdomyosarcoma). Because ALK is normally only expressed in embryos and neonatal brain tissue, any expression after birth in any tissue other than brain tissue is abnormal. The N-methyl-N-nitroso-guandine human ostesarcoma transforming gene (MET) receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. This is more of a potential target in aveolar rhabdomyosarcoma than in embryonal rhabdomyosarcoma. Over-expression of MET/HGF is more common with aveolar rhabdomyosarcoma. Interestingly, though in other cancers (glioblastoma, for example) patients that have been exposed to bevacizumab (which Brody has taken this for over a year), the MET/HGF pathway plays a critical role in invasion (metastasis) when vascular endothelial growth factor (VEGF) has been inhibited. Bevacizumab is a VEGF inhibitor. Blocking VEGF is a mechanism to block angiogenesis (formation of new blood vessels....tumors can't continue to grow if they can't form new blood vessels to supply them). HGF is a protein that controls the growth and movement of cells. VEGF can decrease HGF signaling. So if VEGF is inhibited by Bevacizumab, there is increased HGF signaling through its receptor MET. For patients with glioblastoma it was found that combining VEGF inhibition and MET inhibition allowed patients the benefits from bevacizumab without developing more invasive tumors. Because, VEGF and HGF/MET signaling pathways are active in a variety of tumors, this combined treatment strategy may also apply to other types of cancer. Since Brody's tumor has been exposed to a VEGF inhibitor (bevacizumab) for quite some time, maybe now the HGF signaling through MET is amplified in his tumor? This, as explained, can lead to increased potential for metastases. A means to block MET/HGF signaling may be very important in treating Brody's tumor. Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to MET. Both receptors are involved in cell proliferation, migration, and invasion, and there is evidence that both are deregulated in cancer. A small-molecule dual inhibitor of RON/c-Met has the potential to inhibit tumor growth and could therefore be useful for the treatment of patients with cancers where RON and/or c-Met are activated. So, anyhow, I am interested in possibly pursuing this trial for Brody. However, the trial is currently closed. The oncologist at Cincinnati Children's said if we decide we should want to participate in this trial, to let him know and our name can be added to the waiting list for it. He explained that this trial will open back-up again but he could not give us a timeline for when this would happen.
The second trial the Cincinnati oncologist told us about is a Phase 1 trial study of TEM-1 antibody, MORb-004 (IND# 103821) now known as Onutuxizumab, in children with relapsed or refractory tumors. The study number is ADVL1213. The oncologist explained that Onutuxizumab is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosailin to play a key role in tumor growth and new blood vessel formation in numerous cancer types. He also cautioned that unfortunately only about 60% of rhabdomyosarcoma cells express endosailin. He stated, "it would be more encouraging if it were more ubiquitous in rhabdomyosarcoma." But he also stated, "60% is also not insignificant." This trial is also not open at this time but we can be added to a waiting list for when it opens should we decide to pursue this option.
The third Phase 1 trial explained to us is no longer offered at Cincinnati Children's Hospital but is still offered at Nationwide Children's Hospital in Columbus, Ohio. This trial uses the oncolytic virus HSV-1716 which is a mutated version of the herpes simplex virus which has been demonstrated to selectively infect cancer cells rather than normal cells. Here is a link with information on this trial.
http://clinicaltrials.gov/show/NCT00931931
The Cincinnati oncologist explained that unfortunately so far the human clinical trials have not been nearly as exciting as the pre-clinical and animal studies. It has not yet cured any of the children that have participated in this trial. And, so far there has only been one child with rhabdomyosarcoma that has participated in this trial. This was a 13 year old who received this treatment back in 2010. A phase 1 trial is a dose-finding trial though. Maybe the correct dose has not yet been given? Phase 1 trials start with low doses and then work upwards. The trial enrolls three children at a time and tests the effects of one dose on each child. If that dose is tolerable then the next set of 3 kids receive a higher dose. It could be more effective as dosages increase. At least I really hope so, anyway. That would be seriously awesome if it worked one day.
We also discussed a little more about the pros and cons of molecular profiling and gene sequencing of cancer cells. I posted in a previous blog post about the opinions concerning this topic of the Cincinnati oncologist. He is not overly impressed so far with the information gained from doing this. Nonetheless he did send a previous biopsy sample of Brody's to have some focused molecular profiling done. He expects the results on this within 2 months and hopes it will provide some useful information to guide decisions later on down the road for us. We did talk to him about having GeneKey do the complete genome on a new biopsy sample. He did not feel that this would provide us with usable information. Basically he felt it would be too much information and that the likelihood is small of drugs being available to act on the pathways that may be shown to be involved in Brody's tumor. I do understand that there is a huge chance that we will not be able to get actionable information from proceeding with GeneKey. But, I can't not try. So I will likely move forward with this analysis anyway.
The news yesterday that Brody's tumor has now infiltrated the spinal column was startling, scary, and certainly surprised us. Apparently each of his CT scans since September show the tumor now within the spinal column. And, unfortunately each scan since September shows it getting a little bigger in this space with each scan. The radiologist at Cincinnati Children's Hospital made this discovery when reviewing the CT scans sent from Toledo Children's Hospital. Nobody from Toledo Children's Hospital had told us that Brody's tumor had infiltrated the spinal column. The Cincinnati team did tell us that it was an "easy miss" not to see it and at first their team did not see it either. In the most recent CT scan it appears there is significant pressure on the nerves within the spinal column. Brody has been having symptoms consistent with these nerves being under pressure. These include: inability to fully empty his bladder, intense shooting pains in his left leg, muscle spasms, and incontinence. He has been having trouble emptying his bladder fully for the past 3 weeks. We have to tell Brody to try to go pee every 30 minutes during the day and then we are now up to letting him go about every 4 hours overnight (compared to every 1 to 2 hours overnight, this is a blessing). If Brody doesn't keep up with this frequency he becomes fluid overloaded and unfortunately the excess fluid tends to accumulate in his groin area. This has caused him very significant discomfort. Three weeks ago Brody was having issues with bowel incontinence. This fortunately has improved and has not been a problem for the past 2 weeks. His muscles spasms seemed more frequent three weeks ago compared to the past 2 weeks too. Of special importance to noticing this, is that Brody received high dose IV cyclophosphamide in addition to temsirolimus and vinrelabine that he normally receives weekly. The cyclophosphamide may have made a difference if we go by symptoms. Also, his bladder emptying started to improve about 5 to 6 days after the cyclophosphamide dose. Then it was stable for awhile and then started becoming more problematic recently (and by recently, I mean just before being due for his next round of IV high dose cyclophosphamide). This makes me think maybe we don't have full resistance to cyclophosphamide and that is still somewhat effective.
Brody has also been having more frequent episodes of random and intense pain in his abdomen. He says these are not his usual pains but different and worse than his "normal" belly pains. He frequently has problems with gas pains, constipation, diarrhea, and nausea. These are fairly normal belly pains for Brody. But lately, he has had a lot more episodes of belly pains that are very intense pain located at the top of his abdomen in the center just below his heart. This morning was a heart wrenching drive into the hospitial as Brody's belly was hurting very bad and he was screaming and crying all the way, "Mommy, please help me!!! Mommy, Mommy, Mommy, It HURTS!! My Belly!!." He was in obvious tremendous pain and I could not do anything to make it stop. Then he started vomited too. It was awful! The vomiting was on top of the pain. The pain was not because he had to vomit. He was still in a lot of pain even after vomiting. Somehow, the pain just finally stopped. Thank Goodness!! This episode lasted for about 45 mins this morning but believe me it felt more like 5 hours to me. I can't imagine how long it must have felt for Brody. I was then physically ill from the stress of the whole event. After Brody finally was better, I was so sick from the stress of it all that I ended up vomiting three times myself before I finally calmed down. I was in utter panic inside. Brody regularly has multiple belly pains each day. But for him, he considers it part of his normal daily life and he is able to cope with them and bare it expecting it to soon go away. He is tremendously strong and a brave young boy with regards to this. Today was different. He was in a panic too and so scared. It was obviously not like anything he normally deals with each day. (He doesn't make a big deal of vomiting either and he didn't today when it was happening on top of all the pain he was experiencing either). He has had some shorter (couple of minutes) episodes of worse than normal pains the past couple of weeks. These were scary too but not like today. I was especially panicked after hearing all the news yesterday at Cincinnati Children's. My mind was going places I did not want it to go. I was thinking, "This is it! It's over! We are going to lose him and watch him suffer terribly first and not be able to do a thing about it!" I fear the suffering far more than his death. Seeing your child go through so much pain is so incredibly awful! I don't have the words.
Yesterday, I talked with our oncologist at Toledo Children's Hospital. He was surprised too to learn that Brody's tumor has infiltrated the spinal column. It was not in the radiologist reports and is not entirely obvious. This knowledge especially helps explain why Brody has had such trouble lately with emptying his bladder. Without knowing this, we were getting very suspicious that it was the temsirolimus he had recently started that was causing the problems. Looks like this is likely not the culprit now.
Temsirolimus is a promising biological in the "war" against rhabdomyosarcoma. Temsirolimus inhibits mTOR signaling, halting the cell cycle at the G1 phase in tumor cells. Cells that are stuck in G1, cannot divide. mTOR inhibition also exhibits anti-angiogenesis activity by reducing levels of HIF-1 and HIF-2 alpha (hypoxia inducible factors) and vascular endothelial growth factor (VEGF). The mTOR pathway has been demonstrated to be aberrantly activated in rhabdomyosarcoma. Temsirolimus also inhibits the Hedgehog pathway. Activation of the hedgehog pathway has been implicated in the development of a variety of cancers. Abnormal activation of the pathway probably leads to development of disease through transformation of adult stem cells into cancer stem cells that give rise to the tumor. A recent study showed that approximately 30% of embryonal rhabdomyosarcomas contain an altered Hedgehog pathway signature consistent with activation of the pathway. (In contrast, the hedgehog pathway is not known to play a significant role in aveolar rhabdomyosarcoma). Since temsirolimus may be targeting some attractive targets in Brody's tumor, I do not want to stop giving Brody this medication as long as he is tolerating it okay and we suspect it may be helping.
The combination of temsirolimus, topotecan, and cyclophosphamide have been used together tolerably. Since Brody has not tried using topotecan and cyclophoshpamide both together and he has been tolerating temsirolimus fine, we have decided to try switching Brody over to using these three medications in combination rather than the vinorelabine, temsirolimus, and cyclophosphamide he is using now. I spent some time researching yesterday various doses and schedules of this combination that have been used especially with respect to the topotecan and cyclophosphamide together. Numerous doses and schedules have been shown to be ineffective in rhabdomyosarcoma when using topotecan and cyclophosphamide together. However, I did find a study that had very encouraging results when using a set dose of cyclophosphamide and topotecan on days 1 thorugh 5 of a 21 day cycle. We will be sure to follow the dosing and schedule of this study for Brody's regimen. (There is a Phase 1 trial in San Francisco for recurrent rhabdomyosarcoma that combines Sirolimus (the active metabolite in temsirolimus), topotecan, and cyclophosphamide. After reviewing what doses and schedules have been used and studied for topotecan plus cyclophosphamide, I would definitely not want to enter this trial. It will be using doses and a schedule of topotecan plus cyclophosphamide that will likely not be effective. The trial will use all lower doses than what has been seen to be effective and do it orally at home every day rather than larger doses for 5 days every 21 days). So our plan is to switch over to this chemo regimen I have just described. We are hoping this will at least help stop the tumor from continuing to get larger (stabilize the disease again). (If this regimen does not work....I do have other chemo regimen ideas that I certainly think are worth trying. And, I know our oncologist here in Toledo is certainly brainstorming some "outside of the box" ideas too).
If we can find a chemo regimen that will stabilize the disease again, then we will proceed with surgery to debulk or remove as much of the tumor again as possible followed by radiation treatments. Then, we would continue with the chemo regimen that was found to stabilize the disease in hopes that it keeps the disease in check/prevents it from progressing for awhile. It is highly likely that even if we find a regimen again that stabilizes the disease again that this stabilization will most likely be only temporary. We are hoping we can at least find another way to gain more time with Brody. (However, I will always continue to keep clinging to that little sliver of hope that Brody will somehow beat this despite the odds. Miracles do happen. You just never know).
In the meantime we are also attempting to move forward with GeneKey. Finding a surgeon to do the biopsy and timing the biopsy without having to delay giving chemo is problematic right now though. Also, the lack of insurance coverage is an issue too. The procedure to obtain the fresh biopsy is not covered by insurance. We will have to pay for this and for the analysis by GeneKey. Our oncologist is actually consulting with neurosurgery at Toledo Hospital regarding the difficulty of obtaining a tissue sample from the tumor that is actively growing in the spinal column. He was thinking that maybe if we could go ahead and remove tumor from at least this area that it would help Brody feel better and we would have a fresh tissue sample to send to GeneKey at the same time. And, maybe we would then have the procedure covered by the insurance company too. I don't know about this option yet. This really depends on the risks involved. Our oncologist was attempting to get us scheduled this weekend for an MRI to evaluate better the tumor involvement in the spinal column to better make a decision regarding this option. Getting scheduled for this weekend did not happen though. We will have to wait and see what becomes of this on Monday. Currently we are just scheduled to start the new chemo regimen on Monday. But maybe we may end up doing an MRI, consult with neurosurgeon and then deciding whether to have surgery to remove the tumor from the spinal column at least. Obviously, this is a pretty big decision too if they say it's reasonably safe to attempt it.
Despite all the craziness of everything going on lately, Brody continues to remain in good spirits through it all. He knows that his tumor is getting bigger and that we are trying to find another way to stop it from getting bigger. We do not tell Brody that his doctors say it's not curable. We figure his chances of beating cancer are much better if he believes he will beat it. Right now that is what he believes. He talks about things he wants to do when he grows up.
It is so hard to hear him talking about things so far in the future. I want him to get to live his life and enjoy the things he wants to do. I don't want to think about going on with life without Brody here with us. I am so ANGRY!! Cancer is so unfair and cruel! I try to tell myself to just calm down and be thankful for all the wonderful times you have got to spend with Brody and be thankful that he is with you right now. Enjoy these moments! Stop worrying and crying over things you cannot control! It's hard though. So very, very hard! People ask me how I am doing all the time and how I am so strong and how I cope? I cope with it because I have no choice but to just do so. I keep functioning and going on because somehow I have to. I tell myself multiple times a day, "take a long deep breath in and slow deep breath out." "Focus on this moment and take things one step and one day at a time." "Deal with tomorrow, tomorrow." So, I am hanging in there but I just so wish cancer would just GO AWAY!
The tumor board at Cincinnati Children's Hospital reviewed Brody's case this week. The meetings we had Thursday were to discuss the group's findings and conclusions with myself, Bill, and Brody. My mom and dad traveled with us to the hospital Thursday and did a great job keeping Brody entertained and happy when the doctors were discussing items that may not be the best news for little Brody to hear at this point. I am quite glad my parents were able to do this for us. Some of the discussions we had to have were definitely not ones I wanted Brody to hear.
The oncologist at Cincinnati Children's Hospital told us several things we really did not want to hear. We learned that Brody's tumor has now infiltrated into the spinal column and there is a suspicious spot on his lung that may be tumor but they aren't sure yet. We were informed that the tumor board at Cincinnati Children's Hospital considers Brody's cancer to be incurable and that it is extremely unlikely that Brody will beat cancer. (This is not the first time we've been told this but it still hurts to hear it again). We were told that we had pretty much done every standard treatment for recurrent rhabdomyosarcoma and that his tumor has been exposed to a tremendous arsenal of chemotherapy agents but yet his tumor still continues to progress. He reassured us that Brody's treatment regimens have been absolutely appropriately chosen. He let us know that we have basically three options as far as chemotherapy at this point: 1) Phase 1 trials, 2) No further Chemotherapy (and possibly no further treatment other than comfort care, 3) Treatment not within a clinical trial. He assured us that any of these options would be appropriate for Brody and it's a very tough decision to make as to how to proceed at this point. He let us know that surgery and radiation treatments may still be an option for Brody too. But the important question is whether or not we should put Brody through another surgery and radiation treaments again. Will it provide him with any significant improvement in quality of life? It's hard to say this is something worth pursuing knowing that the tumor cannot be completely removed surgically and that it will certainly continue to grow and recur. It's more reasonable to consider if a chemotherapy option is found that significantly slows or stabilizes the disease and that we could expect a significant increase in the amount of time and quality of life for and with Brody. It was also discussed that radiation treatments could be done to the spinal column area to decrease the size of the tumor in that area to help improve Brody's symptoms. Fortunately, although Brody's tumor has entered the spinal column, it is not yet touching the spinal cord. Radiation treatments would not be possible around the spinal cord. We were surprised to learn that the radiation oncologist at Cincinnati Children's Hosptial still felt Brody could benefit from radiation treatments. When Brody's tumor recurred, it came back growing right in the pins that were used to mark where exactly to deliver his previous radiation treatments. The tumor was concentrated in an area that was known to have been hit very hard with radiation already. But we were told that sometimes, radiation treatments may still work anyway in cases like this. I guess we won't know until we try it. (Brody's radiation oncologist in Toledo did not feel that Brody's recurrent tumor would respond to further radiation treatments). We were also informed that if we decided surgical resection or debulking of as much as possible of Brody's tumor, that the radiation oncologist would have the surgeon place a "sleeve" to pull the bowel away from the area where the tumor is removed. He would want to do this so that radiation treatments could follow after Brody has healed from surgery to the area the tumor had been before surgery. The bowel cannot withstand very large doses of radiation and so if they can pull the bowel away from this area then they could provide higher amounts of radiation treatments.
The oncologist at Cincinnati Children's Hospital discussed each of the Phase 1 trials he felt would be most appropriate for us to consider for Brody. Two of them would be offered at Cincinnati Children's and one of them is offered in Columbus, Ohio at Nationwide Children's Hospital.
The first trial the oncologist told us about combines the novel drug, Crizotinib with conventional chemotherapy. The trial number is ADVL1212. He felt this trial may be of particular interest for us to consider because the conventional chemotherapy used in it is a combination Brody has not yet tried. The "conventional chemotherapy" in this trial is the combination of Topotecan and Cyclophosphamide. Brody has, however, taken Irrinotecan which is very similar to Topotecan. And, Brody has taken A LOT of Cyclophosphamide. Brody was not taking cyclophosphamide though while he was on irrinotecan. He was taking Vincristine and irrinotecan together. The tumor grew very quickly when he was on this combination. So, initially I was not very enthusiastic about this trial even though it did add a novel drug with some exciting potential for treating rhabdomyosarcoma into the mix of agents that Brody has been exposed to before or exposed to a very similar drug. Crizotinib is a medication that is one I have been certainly wanting to have Brody try but I was hesitant about the idea of the combination of Topetecan and Cyclophosphamide due to Brody's lack of response in the past to irrinotecan and that he has been taking cyclophosphamide for a long time and yet the tumor is growing. (I do think it would be growing a lot faster without the cyclophosphamide though). After giving it some more thought though, I do think this trial is one that is worthy of consideration for Brody. There have been cases of tumors responding to Topotecan that did not respond to Irrinotecan. In fact, there are trials that combine both of these drugs into the same regimen even though they are very similar medications since if a tumor is resistant to one it may not still be resistant to the other. So maybe Topotecan is worth a try. Crizotinib is a tyrosine kinase inhibitor, which inhibits anaplasitc lymphoma kinase (ALK), Hepatocyte Growth Factor Receptor (HGFR, C-MET), and Recepteur d'Origine Nantais (RON). ALK gene abnormalities due to mutations or translocations may result in expression of oncogenic fusion proteins (eg, ALK fusion protein) which alter signaling and expression and result in cellular proliferation and survival in tumors which express these proteins. ALK expression is found in 15-32% of embryonal rhabdomyosarcomas and 45-81% of alveolar rhabdomyosarcomas. (Brody has embryonal rhabdomyosarcoma). Because ALK is normally only expressed in embryos and neonatal brain tissue, any expression after birth in any tissue other than brain tissue is abnormal. The N-methyl-N-nitroso-guandine human ostesarcoma transforming gene (MET) receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. This is more of a potential target in aveolar rhabdomyosarcoma than in embryonal rhabdomyosarcoma. Over-expression of MET/HGF is more common with aveolar rhabdomyosarcoma. Interestingly, though in other cancers (glioblastoma, for example) patients that have been exposed to bevacizumab (which Brody has taken this for over a year), the MET/HGF pathway plays a critical role in invasion (metastasis) when vascular endothelial growth factor (VEGF) has been inhibited. Bevacizumab is a VEGF inhibitor. Blocking VEGF is a mechanism to block angiogenesis (formation of new blood vessels....tumors can't continue to grow if they can't form new blood vessels to supply them). HGF is a protein that controls the growth and movement of cells. VEGF can decrease HGF signaling. So if VEGF is inhibited by Bevacizumab, there is increased HGF signaling through its receptor MET. For patients with glioblastoma it was found that combining VEGF inhibition and MET inhibition allowed patients the benefits from bevacizumab without developing more invasive tumors. Because, VEGF and HGF/MET signaling pathways are active in a variety of tumors, this combined treatment strategy may also apply to other types of cancer. Since Brody's tumor has been exposed to a VEGF inhibitor (bevacizumab) for quite some time, maybe now the HGF signaling through MET is amplified in his tumor? This, as explained, can lead to increased potential for metastases. A means to block MET/HGF signaling may be very important in treating Brody's tumor. Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to MET. Both receptors are involved in cell proliferation, migration, and invasion, and there is evidence that both are deregulated in cancer. A small-molecule dual inhibitor of RON/c-Met has the potential to inhibit tumor growth and could therefore be useful for the treatment of patients with cancers where RON and/or c-Met are activated. So, anyhow, I am interested in possibly pursuing this trial for Brody. However, the trial is currently closed. The oncologist at Cincinnati Children's said if we decide we should want to participate in this trial, to let him know and our name can be added to the waiting list for it. He explained that this trial will open back-up again but he could not give us a timeline for when this would happen.
The second trial the Cincinnati oncologist told us about is a Phase 1 trial study of TEM-1 antibody, MORb-004 (IND# 103821) now known as Onutuxizumab, in children with relapsed or refractory tumors. The study number is ADVL1213. The oncologist explained that Onutuxizumab is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosailin to play a key role in tumor growth and new blood vessel formation in numerous cancer types. He also cautioned that unfortunately only about 60% of rhabdomyosarcoma cells express endosailin. He stated, "it would be more encouraging if it were more ubiquitous in rhabdomyosarcoma." But he also stated, "60% is also not insignificant." This trial is also not open at this time but we can be added to a waiting list for when it opens should we decide to pursue this option.
The third Phase 1 trial explained to us is no longer offered at Cincinnati Children's Hospital but is still offered at Nationwide Children's Hospital in Columbus, Ohio. This trial uses the oncolytic virus HSV-1716 which is a mutated version of the herpes simplex virus which has been demonstrated to selectively infect cancer cells rather than normal cells. Here is a link with information on this trial.
http://clinicaltrials.gov/show/NCT00931931
The Cincinnati oncologist explained that unfortunately so far the human clinical trials have not been nearly as exciting as the pre-clinical and animal studies. It has not yet cured any of the children that have participated in this trial. And, so far there has only been one child with rhabdomyosarcoma that has participated in this trial. This was a 13 year old who received this treatment back in 2010. A phase 1 trial is a dose-finding trial though. Maybe the correct dose has not yet been given? Phase 1 trials start with low doses and then work upwards. The trial enrolls three children at a time and tests the effects of one dose on each child. If that dose is tolerable then the next set of 3 kids receive a higher dose. It could be more effective as dosages increase. At least I really hope so, anyway. That would be seriously awesome if it worked one day.
We also discussed a little more about the pros and cons of molecular profiling and gene sequencing of cancer cells. I posted in a previous blog post about the opinions concerning this topic of the Cincinnati oncologist. He is not overly impressed so far with the information gained from doing this. Nonetheless he did send a previous biopsy sample of Brody's to have some focused molecular profiling done. He expects the results on this within 2 months and hopes it will provide some useful information to guide decisions later on down the road for us. We did talk to him about having GeneKey do the complete genome on a new biopsy sample. He did not feel that this would provide us with usable information. Basically he felt it would be too much information and that the likelihood is small of drugs being available to act on the pathways that may be shown to be involved in Brody's tumor. I do understand that there is a huge chance that we will not be able to get actionable information from proceeding with GeneKey. But, I can't not try. So I will likely move forward with this analysis anyway.
The news yesterday that Brody's tumor has now infiltrated the spinal column was startling, scary, and certainly surprised us. Apparently each of his CT scans since September show the tumor now within the spinal column. And, unfortunately each scan since September shows it getting a little bigger in this space with each scan. The radiologist at Cincinnati Children's Hospital made this discovery when reviewing the CT scans sent from Toledo Children's Hospital. Nobody from Toledo Children's Hospital had told us that Brody's tumor had infiltrated the spinal column. The Cincinnati team did tell us that it was an "easy miss" not to see it and at first their team did not see it either. In the most recent CT scan it appears there is significant pressure on the nerves within the spinal column. Brody has been having symptoms consistent with these nerves being under pressure. These include: inability to fully empty his bladder, intense shooting pains in his left leg, muscle spasms, and incontinence. He has been having trouble emptying his bladder fully for the past 3 weeks. We have to tell Brody to try to go pee every 30 minutes during the day and then we are now up to letting him go about every 4 hours overnight (compared to every 1 to 2 hours overnight, this is a blessing). If Brody doesn't keep up with this frequency he becomes fluid overloaded and unfortunately the excess fluid tends to accumulate in his groin area. This has caused him very significant discomfort. Three weeks ago Brody was having issues with bowel incontinence. This fortunately has improved and has not been a problem for the past 2 weeks. His muscles spasms seemed more frequent three weeks ago compared to the past 2 weeks too. Of special importance to noticing this, is that Brody received high dose IV cyclophosphamide in addition to temsirolimus and vinrelabine that he normally receives weekly. The cyclophosphamide may have made a difference if we go by symptoms. Also, his bladder emptying started to improve about 5 to 6 days after the cyclophosphamide dose. Then it was stable for awhile and then started becoming more problematic recently (and by recently, I mean just before being due for his next round of IV high dose cyclophosphamide). This makes me think maybe we don't have full resistance to cyclophosphamide and that is still somewhat effective.
Brody has also been having more frequent episodes of random and intense pain in his abdomen. He says these are not his usual pains but different and worse than his "normal" belly pains. He frequently has problems with gas pains, constipation, diarrhea, and nausea. These are fairly normal belly pains for Brody. But lately, he has had a lot more episodes of belly pains that are very intense pain located at the top of his abdomen in the center just below his heart. This morning was a heart wrenching drive into the hospitial as Brody's belly was hurting very bad and he was screaming and crying all the way, "Mommy, please help me!!! Mommy, Mommy, Mommy, It HURTS!! My Belly!!." He was in obvious tremendous pain and I could not do anything to make it stop. Then he started vomited too. It was awful! The vomiting was on top of the pain. The pain was not because he had to vomit. He was still in a lot of pain even after vomiting. Somehow, the pain just finally stopped. Thank Goodness!! This episode lasted for about 45 mins this morning but believe me it felt more like 5 hours to me. I can't imagine how long it must have felt for Brody. I was then physically ill from the stress of the whole event. After Brody finally was better, I was so sick from the stress of it all that I ended up vomiting three times myself before I finally calmed down. I was in utter panic inside. Brody regularly has multiple belly pains each day. But for him, he considers it part of his normal daily life and he is able to cope with them and bare it expecting it to soon go away. He is tremendously strong and a brave young boy with regards to this. Today was different. He was in a panic too and so scared. It was obviously not like anything he normally deals with each day. (He doesn't make a big deal of vomiting either and he didn't today when it was happening on top of all the pain he was experiencing either). He has had some shorter (couple of minutes) episodes of worse than normal pains the past couple of weeks. These were scary too but not like today. I was especially panicked after hearing all the news yesterday at Cincinnati Children's. My mind was going places I did not want it to go. I was thinking, "This is it! It's over! We are going to lose him and watch him suffer terribly first and not be able to do a thing about it!" I fear the suffering far more than his death. Seeing your child go through so much pain is so incredibly awful! I don't have the words.
Yesterday, I talked with our oncologist at Toledo Children's Hospital. He was surprised too to learn that Brody's tumor has infiltrated the spinal column. It was not in the radiologist reports and is not entirely obvious. This knowledge especially helps explain why Brody has had such trouble lately with emptying his bladder. Without knowing this, we were getting very suspicious that it was the temsirolimus he had recently started that was causing the problems. Looks like this is likely not the culprit now.
Temsirolimus is a promising biological in the "war" against rhabdomyosarcoma. Temsirolimus inhibits mTOR signaling, halting the cell cycle at the G1 phase in tumor cells. Cells that are stuck in G1, cannot divide. mTOR inhibition also exhibits anti-angiogenesis activity by reducing levels of HIF-1 and HIF-2 alpha (hypoxia inducible factors) and vascular endothelial growth factor (VEGF). The mTOR pathway has been demonstrated to be aberrantly activated in rhabdomyosarcoma. Temsirolimus also inhibits the Hedgehog pathway. Activation of the hedgehog pathway has been implicated in the development of a variety of cancers. Abnormal activation of the pathway probably leads to development of disease through transformation of adult stem cells into cancer stem cells that give rise to the tumor. A recent study showed that approximately 30% of embryonal rhabdomyosarcomas contain an altered Hedgehog pathway signature consistent with activation of the pathway. (In contrast, the hedgehog pathway is not known to play a significant role in aveolar rhabdomyosarcoma). Since temsirolimus may be targeting some attractive targets in Brody's tumor, I do not want to stop giving Brody this medication as long as he is tolerating it okay and we suspect it may be helping.
The combination of temsirolimus, topotecan, and cyclophosphamide have been used together tolerably. Since Brody has not tried using topotecan and cyclophoshpamide both together and he has been tolerating temsirolimus fine, we have decided to try switching Brody over to using these three medications in combination rather than the vinorelabine, temsirolimus, and cyclophosphamide he is using now. I spent some time researching yesterday various doses and schedules of this combination that have been used especially with respect to the topotecan and cyclophosphamide together. Numerous doses and schedules have been shown to be ineffective in rhabdomyosarcoma when using topotecan and cyclophosphamide together. However, I did find a study that had very encouraging results when using a set dose of cyclophosphamide and topotecan on days 1 thorugh 5 of a 21 day cycle. We will be sure to follow the dosing and schedule of this study for Brody's regimen. (There is a Phase 1 trial in San Francisco for recurrent rhabdomyosarcoma that combines Sirolimus (the active metabolite in temsirolimus), topotecan, and cyclophosphamide. After reviewing what doses and schedules have been used and studied for topotecan plus cyclophosphamide, I would definitely not want to enter this trial. It will be using doses and a schedule of topotecan plus cyclophosphamide that will likely not be effective. The trial will use all lower doses than what has been seen to be effective and do it orally at home every day rather than larger doses for 5 days every 21 days). So our plan is to switch over to this chemo regimen I have just described. We are hoping this will at least help stop the tumor from continuing to get larger (stabilize the disease again). (If this regimen does not work....I do have other chemo regimen ideas that I certainly think are worth trying. And, I know our oncologist here in Toledo is certainly brainstorming some "outside of the box" ideas too).
If we can find a chemo regimen that will stabilize the disease again, then we will proceed with surgery to debulk or remove as much of the tumor again as possible followed by radiation treatments. Then, we would continue with the chemo regimen that was found to stabilize the disease in hopes that it keeps the disease in check/prevents it from progressing for awhile. It is highly likely that even if we find a regimen again that stabilizes the disease again that this stabilization will most likely be only temporary. We are hoping we can at least find another way to gain more time with Brody. (However, I will always continue to keep clinging to that little sliver of hope that Brody will somehow beat this despite the odds. Miracles do happen. You just never know).
In the meantime we are also attempting to move forward with GeneKey. Finding a surgeon to do the biopsy and timing the biopsy without having to delay giving chemo is problematic right now though. Also, the lack of insurance coverage is an issue too. The procedure to obtain the fresh biopsy is not covered by insurance. We will have to pay for this and for the analysis by GeneKey. Our oncologist is actually consulting with neurosurgery at Toledo Hospital regarding the difficulty of obtaining a tissue sample from the tumor that is actively growing in the spinal column. He was thinking that maybe if we could go ahead and remove tumor from at least this area that it would help Brody feel better and we would have a fresh tissue sample to send to GeneKey at the same time. And, maybe we would then have the procedure covered by the insurance company too. I don't know about this option yet. This really depends on the risks involved. Our oncologist was attempting to get us scheduled this weekend for an MRI to evaluate better the tumor involvement in the spinal column to better make a decision regarding this option. Getting scheduled for this weekend did not happen though. We will have to wait and see what becomes of this on Monday. Currently we are just scheduled to start the new chemo regimen on Monday. But maybe we may end up doing an MRI, consult with neurosurgeon and then deciding whether to have surgery to remove the tumor from the spinal column at least. Obviously, this is a pretty big decision too if they say it's reasonably safe to attempt it.
Despite all the craziness of everything going on lately, Brody continues to remain in good spirits through it all. He knows that his tumor is getting bigger and that we are trying to find another way to stop it from getting bigger. We do not tell Brody that his doctors say it's not curable. We figure his chances of beating cancer are much better if he believes he will beat it. Right now that is what he believes. He talks about things he wants to do when he grows up.
It is so hard to hear him talking about things so far in the future. I want him to get to live his life and enjoy the things he wants to do. I don't want to think about going on with life without Brody here with us. I am so ANGRY!! Cancer is so unfair and cruel! I try to tell myself to just calm down and be thankful for all the wonderful times you have got to spend with Brody and be thankful that he is with you right now. Enjoy these moments! Stop worrying and crying over things you cannot control! It's hard though. So very, very hard! People ask me how I am doing all the time and how I am so strong and how I cope? I cope with it because I have no choice but to just do so. I keep functioning and going on because somehow I have to. I tell myself multiple times a day, "take a long deep breath in and slow deep breath out." "Focus on this moment and take things one step and one day at a time." "Deal with tomorrow, tomorrow." So, I am hanging in there but I just so wish cancer would just GO AWAY!
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