1st FOLFOX treatment and found out KRAS positive

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

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 Reference

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.

https://targetedcancercare.massgeneral.org/My-Trial-Guide/Diseases/Colorectal-Cancer/KRAS/G12V-(c-35G-T).aspx

caregiver3 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.

When I talked to my Oncologist about the throat closing up, he told me that it is just the sensation and that the throat does not close up. So no chance of anything serious happening.  

Tru

www.medicalxpress.com/print431597643.html

caregiver3 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

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 Reference

The 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.

https://targetedcancercare.massgeneral.org/My-Trial-Guide/Diseases/Colorectal-Cancer/KRAS/G12V-(c-35G-T).aspx

 

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.