1st FOLFOX treatment and found out KRAS positive
Well, my dh just got disconnected from the pump today and completed his first round of FOLFOX. Avastin will be added next time. His side effects have been cold issues with eating and drinking. He can't even handle room temp. He drank room temp water and his throat closed up and he couldn't speak! It scared me! He also has this weird sensation when he chews. He also has been very tired and sleeping a lot. We also found out that he is KRAS G12V positive. Anyone have any experience with KRAS?
Comments
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Folfox
It's a hard combination and the oxi is a terrible one that is prescribed. The food sensation has been called "first chew syndrome" and your whole mouth feels terrible and tingles terrible. Almost like you ate a whole mouth full of sour candy. It is normal and it can last unfortunately for quite some time. The cold sensitivity is another thing that is very normal. Make sure he doesn't get in the cold section of a market or in places (if you live in warm climate) that have air conditioning. Also let him know that going in the refridge is going to be a problem now and he should be aware of sensitivity to this. I'm not able to help you with the the other issue, but please let us know if he is experiencing any other side effects or issues that we might be able to address. Wishing him the best through this treatment - it's hard and we are here to help him. Being disconnected from pump leaves you exhausted so be aware of that also.
Kim
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I find room temperature is a
I find room temperature is a bit on the cold for me as well after my IV drip treatment. Especially the immediate week after. Everything has to be heat up for me. The 2nd week on I can tolerate the room temperature.
One of our members, Mikenh, has some knowledge on KRAS. He may be able to answer that question for you.
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KRAS is a gene that provides
KRAS is a gene that provides the code for making a protein, KRAS, which is involved primarily in controlling cell division. This protein is part of the MAP kinase signaling cascade (RAS/RAF/MEK/ERK) that relays chemical signals from outside the cell to the cell's nucleus and is primarily involved in controlling cell division. KRAS is an enzyme (a GTPase) that converts a molecule called GTP into GDP. When KRAS is attached (bound) to GDP, it's in its "off" position and can't send signals to the nucleus. But when a GTP molecule arrives and binds to KRAS, KRAS is activated and sends its signal, and then it converts the GTP into GDP and returns to the "off" position.
When mutated, KRAS can act as an oncogene, causing normal cells to become cancerous. The mutations can shift the KRAS protein into the "on" position all the time. KRAS mutations are common in pancreatic, lung and colorectal cancers. These KRAS mutations are said to be somatic, because instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous.
Tumor mutation profiling performed clinically at the MGH Cancer Center has identified KRAS mutations across a broad-spectrum of cancer types. The highest incidence of KRAS mutations have been found in pancreatic cancer (70%), colon cancer (30%), lung cancer (25%), cholangiocarcinoma (15-20%), acute myeloid leukemia (15-20%) and endometrial cancer (15-20%). Across the other major tumor types, KRAS mutations have been found in less than 10% of cases that have been tested.
Source: Genetics Home ReferenceThe KRAS G12V mutation arises from a single nucleotide change (c.35G>T) and results in an amino acid substitution of the glycine (G) at position 12 by a valine (V).
There is no clear association between activating KRAS mutations and poor prognosis in colorectal cancer. This may be attributed to allele-specific differences, as the KRAS G12V mutation has specifically been associated with worse survival. In addition, the presence of BRAF mutations significantly worsens the prognosis and clinical trials looking for the effect of KRAS on long-term outcomes should control for this factor.
Currently, the presence of KRAS mutations in colorectal cancer is used more as a negative marker of treatment selection. Based on FDA guidelines, metastatic colorectal patients harboring a KRAS mutation should NOT be treated with the anti-EGFR agent cetuximab or panitumumab, regardless of EGFR expression status. Furthermore, preclinical studies have strongly indicated that clinical BRAF inhibitors should NOT be used in the treatment of KRAS-mutant colorectal cancer, due to unexpected compensatory mechanisms.
The role of KRAS mutations in predicting response to other targeted therapies has not yet been determined. While it remains unclear whether KRAS mutation will predict response to current MEK and/or ERK inhibitors being tested in clinical trials, a combination therapy approach that additionally targets the PI3K/AKT/mTOR or insulin growth factor receptor pathways may confer more robust treatment effects.0 -
There is a National
There is a National Institutes of Health Clinical Research Study on KRAS G12V for patients with the HLA-A 1101 Allele that is currently recruiting patients and information is at https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2017-C-0113.html and they are using an immunotherapy approach. This is only for Stage 4 unresectable patients and the patient has to have the HLA-A 1101 Allele. There's a similar trial for my cancer, G12D, and I'm going to get tested for the required Alleles as a backup for my current standard treatment.
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Thank you so much for the info!Mikenh said:There is a National
There is a National Institutes of Health Clinical Research Study on KRAS G12V for patients with the HLA-A 1101 Allele that is currently recruiting patients and information is at https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2017-C-0113.html and they are using an immunotherapy approach. This is only for Stage 4 unresectable patients and the patient has to have the HLA-A 1101 Allele. There's a similar trial for my cancer, G12D, and I'm going to get tested for the required Alleles as a backup for my current standard treatment.
I appreciate you posting all of this info on KRAS! Sounds like it makes his cancer more complicated! The one thing that stood out to me was the worse survival in the G12V. That just means he will have to fight that much harder! So we need to ask for the further testing with the Alleles too. He is stage 4, right now we are supposed to meet with a liver surgeon hoping that his liver can be resected. The plan now is 3 months of FOLFOX with Avastin then a break then liver resection, but this depends on alot. He has already had his primary tumor in his sigmoid colon and rectum resected. It was blocking him off and we didn't know about the liver yet. He also has "possible" lung metastasis too but these haven't been confirmed. Again, thank you so much for posting all of this info, it helps alot!
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Problem with his eyes tooAnnabelle41415 said:Folfox
It's a hard combination and the oxi is a terrible one that is prescribed. The food sensation has been called "first chew syndrome" and your whole mouth feels terrible and tingles terrible. Almost like you ate a whole mouth full of sour candy. It is normal and it can last unfortunately for quite some time. The cold sensitivity is another thing that is very normal. Make sure he doesn't get in the cold section of a market or in places (if you live in warm climate) that have air conditioning. Also let him know that going in the refridge is going to be a problem now and he should be aware of sensitivity to this. I'm not able to help you with the the other issue, but please let us know if he is experiencing any other side effects or issues that we might be able to address. Wishing him the best through this treatment - it's hard and we are here to help him. Being disconnected from pump leaves you exhausted so be aware of that also.
Kim
I forgot to mention that he is also having an issue with his eyes. They have been tearing up and burning and making his vision funny. We can't figure out if it is a light sensation or from cold.
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Tearinesscaregiver3 said:Problem with his eyes too
I forgot to mention that he is also having an issue with his eyes. They have been tearing up and burning and making his vision funny. We can't figure out if it is a light sensation or from cold.
Teariness (lacrimation) is a known side-effect of 5-flurouracil (5-FU), one of the components of the FOLFOX regimen. I'm on FOLFIRI, which also has 5-FU, and I occasionally tear up.
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Some background links on theMikenh said:There is a National
There is a National Institutes of Health Clinical Research Study on KRAS G12V for patients with the HLA-A 1101 Allele that is currently recruiting patients and information is at https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2017-C-0113.html and they are using an immunotherapy approach. This is only for Stage 4 unresectable patients and the patient has to have the HLA-A 1101 Allele. There's a similar trial for my cancer, G12D, and I'm going to get tested for the required Alleles as a backup for my current standard treatment.
Some background links on the trial (note that you must have that particular Allele. It is hoped that other Alleles and mutations will be tested so that Immunotherapy options expand to other types of cancer but this is really early stages. These links mostly refer to MRAS G12D and the HLA-C 0802 allele but the same theory applies to the G12V study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178827/pdf/nihms836415.pdf
https://cancerriot.blogspot.ca/search?updated-max=2016-08-10T10:37:00-04:00&max-results=7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775432/pdf/nihms747004.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1878537/pdf/JCI0732446.pdf
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Bothcaregiver3 said:Problem with his eyes too
I forgot to mention that he is also having an issue with his eyes. They have been tearing up and burning and making his vision funny. We can't figure out if it is a light sensation or from cold.
They can tear up for both reasons. Eyes can become very sensitive especially in the sun. Make sure he wears a hat if sunny out. The drugs affect everyone different but I've had both problems. Hope it gets better.
Kim
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That happened to me aftercaregiver3 said:Problem with his eyes too
I forgot to mention that he is also having an issue with his eyes. They have been tearing up and burning and making his vision funny. We can't figure out if it is a light sensation or from cold.
That happened to me after first treatment (start my secodn next monday)- and my eyes stung badly when exposed to a little wind and sunshine
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i ws told to breath into my
i ws told to breath into my elbow or cupped hands in order to get warm air to my throat IF I shoudl get the throat issue- but so far I haven't had it- even with fridge cold drinks- but i do get the needle/tingling feelign in hands when handling cold stuff- perhaps take a drink and immediately breath into cupped hands for a few times- might help
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He is just now feeling better!
He started having more side effects. Sneezing and his nose pouring all the time. And add shortness of breath to the list. He was seen by a doctor today to check all that. They listened to his lungs and checked his nose and throat and ears out. Said it didn't seem like a cold and that some people can have side effects like this and it can mess with the mucus membranes or something like that. He is still very worn out even a week later. Looks like this could get rough for him.
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Thanks so muchMikenh said:Some background links on the
Some background links on the trial (note that you must have that particular Allele. It is hoped that other Alleles and mutations will be tested so that Immunotherapy options expand to other types of cancer but this is really early stages. These links mostly refer to MRAS G12D and the HLA-C 0802 allele but the same theory applies to the G12V study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178827/pdf/nihms836415.pdf
https://cancerriot.blogspot.ca/search?updated-max=2016-08-10T10:37:00-04:00&max-results=7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775432/pdf/nihms747004.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1878537/pdf/JCI0732446.pdf
for the links!! Great info!
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Very good background paper on Ras (K, N, H)Mikenh said:KRAS is a gene that provides
KRAS is a gene that provides the code for making a protein, KRAS, which is involved primarily in controlling cell division. This protein is part of the MAP kinase signaling cascade (RAS/RAF/MEK/ERK) that relays chemical signals from outside the cell to the cell's nucleus and is primarily involved in controlling cell division. KRAS is an enzyme (a GTPase) that converts a molecule called GTP into GDP. When KRAS is attached (bound) to GDP, it's in its "off" position and can't send signals to the nucleus. But when a GTP molecule arrives and binds to KRAS, KRAS is activated and sends its signal, and then it converts the GTP into GDP and returns to the "off" position.
When mutated, KRAS can act as an oncogene, causing normal cells to become cancerous. The mutations can shift the KRAS protein into the "on" position all the time. KRAS mutations are common in pancreatic, lung and colorectal cancers. These KRAS mutations are said to be somatic, because instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous.
Tumor mutation profiling performed clinically at the MGH Cancer Center has identified KRAS mutations across a broad-spectrum of cancer types. The highest incidence of KRAS mutations have been found in pancreatic cancer (70%), colon cancer (30%), lung cancer (25%), cholangiocarcinoma (15-20%), acute myeloid leukemia (15-20%) and endometrial cancer (15-20%). Across the other major tumor types, KRAS mutations have been found in less than 10% of cases that have been tested.
Source: Genetics Home ReferenceThe KRAS G12V mutation arises from a single nucleotide change (c.35G>T) and results in an amino acid substitution of the glycine (G) at position 12 by a valine (V).
There is no clear association between activating KRAS mutations and poor prognosis in colorectal cancer. This may be attributed to allele-specific differences, as the KRAS G12V mutation has specifically been associated with worse survival. In addition, the presence of BRAF mutations significantly worsens the prognosis and clinical trials looking for the effect of KRAS on long-term outcomes should control for this factor.
Currently, the presence of KRAS mutations in colorectal cancer is used more as a negative marker of treatment selection. Based on FDA guidelines, metastatic colorectal patients harboring a KRAS mutation should NOT be treated with the anti-EGFR agent cetuximab or panitumumab, regardless of EGFR expression status. Furthermore, preclinical studies have strongly indicated that clinical BRAF inhibitors should NOT be used in the treatment of KRAS-mutant colorectal cancer, due to unexpected compensatory mechanisms.
The role of KRAS mutations in predicting response to other targeted therapies has not yet been determined. While it remains unclear whether KRAS mutation will predict response to current MEK and/or ERK inhibitors being tested in clinical trials, a combination therapy approach that additionally targets the PI3K/AKT/mTOR or insulin growth factor receptor pathways may confer more robust treatment effects.There's a good paper on the history of Ras and the attempts to conquer it with drugs over the past 30 years and the reasons why those efforts failed. It also talks a little about the future though with few details. They do not talk about the NCI work. It's in the American Association for the Advancement of Science in the March 17, 2017 edition. It's also behind a paywall - you'd need access to a research library to read it.
There's another article, Drugging the 'undruggable' cancer targets in Nature, August 2017, Volume 17. I managed to get a PDF off the web but I don't have the link to the article where I can look at it for free anymore. It does talk about the NCI stuff.
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