PET Scan Results

We saw Dr. Sharma today, the oncologist after the 2 1/2 hour PET scan. Although I have not seen the written report yet, this is what was found: Curtis has cancer in lymph nodes in his lungs, more in his abdomen and possibly in his liver. They also did genetic testing to see how well his genes will respond to chemotherapy. His genes look very good and they expect he will respond well. They also provided information about a clinical trial of Everolimus (RAD001, Afinitor) to be used with Folfox (5FU, Oxaliplatin, Leucovorin) and Avastin. We go back tomorrow morning for blood work and to do tests for the clinical trial. The oncologist said that he thinks Curtis has a 60-70% of the cancer responding to this chemo. After 2 months (or 4 cycles) of chemo, they will do another PET scan to see how he is responding. He will go in for 6 hours of infusion of Leucovorin, Oxaliplatin and Avastin. He will go home with the infusion ball of 5FU for 46 hours and will have a home health nurse come and de-access his port. He should start this week. Here is information about how each chemotherapy drug works:

How 5-FU works:
Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue.   "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition.  Cancerous cells lose this ability.  Cancer cells no longer have the normal checks and balances in place that control and limit cell division.  The process of cell division, whether normal or cancerous cells, is through the cell cycle.  The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).
The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division.  Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division.  If the cells are unable to divide, they die.  The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink.  They also induce cell suicide (self-death or apoptosis).
Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific.  Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific.  The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective.  This is why chemotherapy is typically given in cycles.
Chemotherapy is most effective at killing cells that are rapidly dividing.  Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The "normal" cells will grow back and be healthy but in the meantime, side effects occur.  The "normal" cells most commonly affected by chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea, and/or hair loss.  Different drugs may affect different parts of the body.
5-FU belongs to the category of chemotherapy called antimetabolites.  Antimetabolites are very similar to normal substances within the cell.  When the cells incorporate these substances into the cellular metabolism, they are unable to divide.  Antimetabolites are cell-cycle specific.  They attack cells at very specific phases in the cycle.  Antimetabolites are classified according to the substances with which they interfere.

How Avastin works:
Monoclonal antibodies are a relatively new type of "targeted" cancer therapy.  Antibodies are part of the immune system.  Normally, the body creates antibodies in response to an antigen (such as a protein in a germ) entering the body.  The antibodies attach to the antigen in order to mark it for destruction by the body's immune system.  In the laboratory, scientists analyze specific antigens on the surface of cancer cells (target) to determine a protein to match the antigen.  Then, using animal and human proteins, scientists work to create a special antibody that will attach to the target antigen.  Antibodies will attach to matching antigens like a key fits a lock.  This technology allows treatment to target specific cells, causing less toxicity to healthy cells.   Monoclonal antibody therapy can be done only for cancers in which antigens (and the respective antibodies) have been identified.
Avastin works by interfering with the process of angiogenesis by targeting and inhibiting human vascular endothelial growth factor (VEGF).  VEGF is a cytokine (a small protein released by cells that have specific effects on the behavior of cells) which when it interacts with its receptors in the cell leads to new blood vessel formation or angiogenesis.

How Oxaliplatin Works:
Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue.   "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition.  Cancerous cells lose this ability.  Cancer cells no longer have the normal checks and balances in place that control and limit cell division.  The process of cell division, whether normal or cancerous cells, is through the cell cycle.  The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).
The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division.  Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division.  If the cells are unable to divide, they die.  The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink.  They also induce cell suicide (self-death or apoptosis).
Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific.  Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific.  The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective.  This is why chemotherapy is typically given in cycles.
Chemotherapy is most effective at killing cells that are rapidly dividing.  Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The "normal" cells will grow back and be healthy but in the meantime, side effects occur.  The "normal" cells most commonly affected by chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea, and/or hair loss.  Different drugs may affect different parts of the body.
Chemotherapy (anti-neoplastic drugs) is divided into five classes based on how they work to kill cancer.  Although these drugs are divided into groups, there is some overlap among some of the specific drugs.  The following are the types of chemotherapy:
Oxaliplatin is classified as an alkylating agent.  Alkylating agents are most active in the resting phase of the cell.  These drugs are cell-cycle non-specific.  There are several types of alkylating agents.

How Afinitor Works:
Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells.  To date, cancer treatment has focused primarily on killing rapidly dividing cells because one feature of cancer cells is that they divide rapidly.  Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects. 
Targeted therapy is about identifying other features of cancer cells.  Scientists look for specific differences in the cancer cells and the normal cells.  This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects.  Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells. 
There are different types of targeted therapies, defined in three broad categories.  Some targeted therapies focus on the internal components and function of the cancer cell.  The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die.  There are several types of targeted therapy that focus on the inner parts of the cells.   Other targeted therapies target receptors that are on the outside of the cell.   Antiangiogenesis inhibitors target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.
Researchers agree that targeted therapies are not a replacement for traditional therapies.  They may best be used in combination with traditional therapies.  More research is needed to identify which cancers may be best treated with targeted therapies and to identify additional targets for more types of cancer. 
Afinitor is an inhibitor of mTOR.  mTOR inibition blocks the translation of genes that regulate cancer cell proliferation.  It also results in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor (VEGF).