• White Blood Cells, abbreviated "WBC"
• Red Blood Cells, abbreviated "RBC"
• Platelets

White Blood Cells = WBC
The WHITE BLOOD CELLS (WBC) are the cells that fight infection. The WBC is usually between 3,500 and 10,000. We shorten this to 3.5 to 10.0. There are 2 main types of WBCs:

• POLYS, also called "segs", "NEUTs" or "granulocytes"
• LYMPHS.

POLYS are the power cells that kill germs
POLYS fight bacterial infection and are the ones we are most concerned about when we look at your blood counts.
The blood technician puts part of your blood specimine in a special machine that counts he number of WBCs. During that, she makes a slide of your blood and counts the number of POLYS and LYMPHS (and a few other cells) in the first 100 cells she sees. This comes out as a percentage. We multiply the percentage of POLYS times the WBC to give us the ABSOLUTE GRANULOCYTE COUNT (abbreviated "AGC"). This number tells us how strong your defenses are.

AGC must be 1.5 or higher to get chemo
Your blood must have recovered to a level of an AGC equal to or greater than 1,500 (or 1.5) to receive your next dose of chemotherapy. We can hasten the AGC recovery by using "fertilizer" for them.

Fertilizer to increase the AGCs
The chemical our own body makes to "fertilize" the bone marrow cells that grow into the white blood cells is called G-CSF (the short form of Granulocyte Colony-Stimulating Factor). The trade name is "Neupogen" (said "NEW poh jen"). This is given as an injection with a very tiny needle, similar to an insulin shot into the tissue just under the skin (not into the muscle), for a number of days during the time when the white blood count is low. This medicine is very expensive, and there are very specific guidelines for when it should be used.

The lowest AGC tells me how strong the chemo was
The time of lowest counts is somewhere between days 10 to 18 after starting each cycle of chemotherapy. That is why I usually like to check a blood count on day 14. I want the AGC on that day to be somewhere between 500 and 1000 to make sure that you are getting enough chemotherapy but not too much. Chances for infection are greater when the AGC is less than 500. However, many patients have counts much lower than that and do not get infection or fever.

Red Blood Cells = Hemoglobin (Hgb)
The Red Blood Cells (RBCs) are really just tiny bags of hemoglobin that float in the plasma liquid. The purpose of the hemoglobin is to carry oxygen to the cells. The normal hemoglobin level is anywhere from 12 to 14, but most people do quite well if the Hgb is 10 or greater. HCT stands for HEMATOCRIT. It is another way of measuring the amount of red blood. It is generally three times the Hgb.

With chemotherapy, most people do not generally run a normal Hgb, but there is nothing dangerous about that usually. If your Hgb is 8.0 or less, you will probably feel very tired and run down and may have some shortness of breath. We generally give blood transfusions if a person has symptoms at that level. However, if I see that the RBCs remain low, I will prescribe "fertilizer" for the RBCs.

"Fertilizer" to increase the Hgb
The chemical our own body makes to "fertilize" the bone marrow cells that form red blood cells is called "erythropoietin" (said "a RITH row POH it ten"), or just "Epo" (said "EE poh"). It is also given as an injection under the skin similar to an insulin shot. However, this is usually given only three times a week and is continued even during chemotherapy. This medicine is also very expensive, and there are very specific guidelines for when it should be used.

Platelets: "Stick 'em up!"
PLATELETS are the little particles in the blood that circulate and plug up any leaks. The normal platelet count is from 150,000 to 450,000. We abbreviate this to 150 to 450. Most people do not have any problems unless the platelet count drops below 20 to 30. Some drugs cause more lowering of the platelet count than others. We generally require the platelet count to be at least 100 before starting each cycle of chemotherapy. No platelet growth factor--yet! Scientists are perfecting the "fertilizer" for platelets. It will be available in the next year or two.

A sample blood count report (Can you calculate the AGC?)

Test	Result	Normal	Test	Result	Normal
WBC	5.0	3.6 - 9.6	Hgb	11.5	12.1-17.2
Lymph%	40	20 - 51	Hct	36	36 - 50
Gran%	60	42 - 75	Plt	177	200 - 386

• fuel-gasoline, not just any kind, only for cars. Airplane fuel won't work.
• an engine to push
• your foot on the accelerator signaling the engine what to do
• a clear road ahead to drive on

If any of these aren't working right, then your car won't "go". Having regular bowel movements requires the same things:

• fuel-bulk and liquid in the diet
• a pusher-that's your colon muscles
• a signal to the colon-that's the brain
• an open path: that's your intestines

If any of these things aren't working right then you won't "go" either. The most common things that go wrong in patients with cancer are:

• WRONG FUEL
• PUSHER can't push effectively

THE PROBLEM with WRONG FUEL: The small intestines take the food from the stomach, where it is usually pretty juicy, add more digestive juices and send it to the COLON or Large Intestine. The COLON is like a big dryer. It sucks all the water out of the stool. This is part of the way humans learned how to survive without being in water. The longer the stool stays in the colon, the more dry and hard it becomes. If it stays there long enough, it becomes tiny little round balls.

NEXT PROBLEM: Pusher can't push effectively
Have you ever seen a kitten nursing? With her paws she pushes first on one side and then on the other of the mother's nipple to squeeze out the milk. The colon works that way too. It is a long tube with muscles that go around it like bracelets. One muscle bracelet squeezes down and the muscle bracelet right next to it stretches open. This happens over and over again down the whole length of the colon's muscle bracelets. This allows the stool to be pushed through to the rectum.

This squeezing process works best if the stool has the consistency of oatmeal. If the stool is hard and in little marble sized pieces, it can't "squirt" or squeeze it along. The little hard balls sit. Sometimes these balls clump together and form a huge hard rock that is very difficult to move along. The "muscle bracelets" of the colon get so stretched out that they can't squeeze down. The big mass of stool barely moves except by gravity and the jostling that comes with activity.

When this big rock finally gets to the rectal area-OUCH, the rectal tissues may not be able to stretch enough to let it pass through. This big rock stretches and tears the lining of the tube (we call these tears "fissures"). The colon's reaction to this pain is to clamp down and make it EVEN HARDER to push the stool through.

ANOTHER PROBLEM: The muscle bracelets are drugged.
Another reason the colon's muscle bracelets can't work is because the muscle bracelets are literally "drugged". One of the side effects of our best pain killer medications is to put the muscles of the colon to sleep. The stronger the pain killer, the more constipation it causes.

WHAT CAN WE DO ABOUT THIS? Lots!

• Get enough bulk or "fiber" in the diet. Fiber comes from fruits and vegetables. Sometimes it's hard to eat enough of them, especially if you don't feel well.

A good way to add fiber is from products like Metamucil or Citracel or PerDiem. I personally prefer the PerDiem because it's easier to take (not gritty) and less messy.

• Drink 6-8 glasses of non caffeinated liquid a day. The fiber will "bulk up" the stool and prevent it from becoming hard marbles only if there is enough water available to keep it about as soft as oatmeal.
• Take Senokot-S tablets. This will counteract the effects of the pain killers on the muscle bracelets of the colon.

Begin with 1 or 2 tablets twice a day. This can be increased up to 4 tablets twice a day. Because Senokot-S causes the muscle braclets to wake up and squeeze, it can cause cramps. If you take too much, it can cause diarrhea. That's why we usually start out with only 1 or 2 twice a day until we know what dose your body needs.

• Be as active as your condition allows. Excercise of any kind-walking, bicycle riding, etc-helps the bowels push the stool as well. Our bodies were made to be active. We just don't work as well when we sit around.
• Get your pain controlled. When we are in pain, our bowels just shut down. The whole body just focuses on getting rid of the pain. Even though the pain meds can cause constipation, it will be less if the pain is controlled.
• Review all your medicines with me. You may have a medicine that adds to the constipation. Sometimes we can change it to another medicine that might not be as constipating.
• Let me check your blood tests for other problems. High calcium, low thyroid, high blood sugars from diabetes, etc., can also add to constipation. These are usually easy to fix.
• Use Lactulose syrup. My nickname for this is "Liquid Plummer". It always works. 3 Tablespoons every 4 hours until a bowel movement occurs. This medicine will cause bloating. Even though it is sweet, however, it is ok for diabetic patients to take because the sugar doesn't get absorbed into the blood. It stays inside the colon.
• We can try an enema. An enema will "flush" the stool from the colon. If the stool has become the big rock that blocks the passage, (we call this "impacted") we can slowly soften it with certain kinds of enemas ("Milk and Molasses" enemas work very well for this.)

Let's work together on this. We can always get things "going" again if we go through each of these steps.

Last updated on Nov 9, 2008

• All services are free
• Address: 9575 Katy Fwy, #428, Houston, TX 77024
• Phone: 713-461-0028
• Web address: www.cancare.org
• Email address: info@cancare.org

Cancer Counseling, Inc.

• Individual or family counseling
• Many locations throughout the city
• Initial 6 sessions are free
• Address: 4101 Greenbriar, #317, Houston, TX 77098
• Phone: 713-520-9873

American Cancer Society:

• 1-800-ACS-2345

• 5 fruits or vegetables a day
• Low saturated fats
• Appropriate number of calories
• Minimal intake of alcohol
• Calcium: 1000 to 1500 mg a day
• Multiple vitamin containing folic acid 400 mg daily
• 8 glasses of water or non-caffeine liquid daily

What about vitamin supplements?
Carefully controlled studies have shown that taking pills is not as good as eating the vegetables or fruits that contain the vitamins. With the exception of folic acid, all of the vitamins that we need come in foods that also contain other important chemicals that help to prevent or reverse cancer. Mom was right: "Eat your vegetables."

What about antioxidants?
The jury is still out for a final decision on that one. However, there is one study, the "Caret" study, which was done in patients who were heavy smokers and who were at risk for getting lung cancer. Patients who took supplements of Vitamin E and beta carotene actually got lung cancer and heart disease more often than patients who didn't take the vitamins.
Until we have more evidence, do as Mom says and "Eat your vegetables (and fruits!)."

What about herbs?
Most herbs are sold as "diet supplements" like broccoli, but are marketed as drugs. Broccoli never had to go through the Food and Drug Administration to prove that it was safe and neither do these herbs. However, many of these herbs contain ingredients that are really drugs. And they often cost as much as prescription medications.

The folks who sell these medications may be well-intentioned and really believe what they are telling you. However, even if these chemicals are "natural" like broccoli, it doesn't mean that they are safe and effective. Petroleum is natural but is certainly not safe or effective to take internally.

The FDA has just recently removed another "diet supplement" from public access because further testing has shown that when the body breaks this product down it is converted into a poison which was banned many years ago. Taking these diet supplements, therefore, is a little bit like playing "Russian Roulette"-you just don't know what might happen. So-enjoy your vegetables and fruits!

Last updated on Nov 9, 2008

Depression

Depression Affects More Than 17 Million Americans
	You are not alone–we can help. This is not a character defect! Your brain is low on vital chemicals. There are VERY EFFECTIVE medicines You won't "get hooked" & they don't have bad side effects. It gets better!

Depression Checklist
If you've had any of these 2 weeks or more, please .

1. The Anti-Aromatase Agents only work in women whose ovaries are no longer working--that is POST-Menopausal women.
2. Exemestane (Aromasin™) is been tested and approved for SPREAD or "metastatic" (stage IV) breast cancer. Clinical trials are currently being done to compare it to Tamoxifen for early stage "adjuvant" (stages I, II, or III) breast cancer.

This link gives other interesting and detailed information about Exemestane. ellence.com

Last updated on Nov 9, 2008

Faslodex™
see Fulvestrant

TOP

Fulvestrant, (Faslodex™)
This is the first of a whole new class of antihormone drugs nicknamed "SERD"--not to be confused with NERDs!. SERD is an acronym that stands for Selective Estrogen Receptor Downregulator.

The Estrogen Receptor (ER) is a special molecule attached to the one GENES on the CHROMOSOME number 17. The ER is activated by a two step process: First, a molecule of Estrogen attaches or "binds" to the special grove in the molecule. Second, it pairs up with another ER that has its Estrogen molecule. These paired molecules are called "dimerized". This "ER Dimer" activates genetic switches that turn on the cell processes of growth, division, even anti-aging!

The SERD damages the ER so it neither "binds" the molecule of estrogen nor "dimerizes". The cell can't divide or grow and is susceptible to aging and (Yay anti-cancer power!) DYING. This is how the SERDs kill cancer cells that require estrogen to grow.

This link to the website sponsored by AstraZeneca, the makers of Fulvestrant (Faslodex™) shows a little animated cartoon how this works.

Fulvestrant (Faslodex™) is given as an injection into the buttock muscle once every 28 days. The link faslodex.com has lots of other important information about Fulvestrant.

Last updated on Nov 9, 2008


Granisetron
see Kytril™


Herbs

• Information on herbs from Memorial Sloan-Kettering Cancer Center

• Persons who are considered "high risk" of getting complications from the flu are over 65, children 6 to 23 months, pregnant women in the 2nd or 3rd trimester during flu season, nursing home patients with chronic diseases such as cancer, especially spread or "metastatic" cancer and receiving chemotherapy or radiation, diabetes, emphysema, chronic bronchitis, and asthma heart failure.
• Healthy patients receiving adjuvant chemotherapy for breast cancer are not at an especially high risk, but it is certainly reasonable to get a flu shot. Children younger than 9 years getting the vaccine for the first time.
• Healthcare workers and household contacts of high risk patients should also get it early.

WHAT IF I GET THE FLU BEFORE I GET MY VACCINATION?
If you get flu symptons before you are vaccinated OR if you get symptoms less than 2 weeks after vaccination (before the vaccine has had time to increase your antibody levels), then you may benefit from treatment with one of the following drugs:
For Type A Virus Infection only:

• Amantadine (Symmetrel is the trade name) 200 mg daily until all flu symptoms have resolved Side effects from Amantadine could be sleeplessness, lightheadesness, nervousness, difficulty concentrating. Much rarer are hallucinations and seizures. The persons who are most likely to have these serious side effects tend to be older patients who are taking other medications that can affect the brain such as drugs for Parkinson's Disease, antihistamines, and anticholinergic drugs. For elderly patients or patients with decreased kidney or liver function, the dose is reduced by half—only one pill a day.
• Ramantidine 100 mg twice a day for 7 days. Rimantadine is much less likely to have side effects.

For Types A & B Infection Symptoms

• START WITHIN 48 HOURS or it will not work! PILL--Oseltamivir (Tamiflu is the trade name) is a 75 mg tablet twice daily for 5 days to after exposure or onset of symptoms The dose must be reduced if the kidneys are not functioning at over 30% of capacity.
• NASAL INHALER--Zanamivir (Relenza is the trade name) is an inhaler that is taken as 2 inhalations twice daily for 5 days Note that persons who already have asthma or bronchitis might find this inhaled medication irritating to their airways. These persons should take the pill instead.

FOR PREVENTION IF YOU CANNOT GET THE VACCINATION

• Amantadine (Symmetrel) 200 mg daily continuing for at least 10 days.
• Rimantadine (Flumadine is the trade name) 100 mg twice a day or 200 mg once a day for a maximum of 42 days can prevent flu infection with the A-type virus in 70-90% of patients Oseltamivir (Tamiflu) 75 mg daily for up to 42 days.
• The nasal inhaler is not approved for prevention.

GENERAL MEASURES FOR "THE FLU" What mom always told you...

• Rest
• Drink plenty of fluids chicken soup really does help
• Take Tylenol or Aspirin or Ibuprofen (Motrin, Advil) if ok with Dr Macheledt or Dr Holmes for the pain and fever
• Gargle for your throat. 1 teaspoon of salt and 1 teaspoon of baking soda in a quart of water can be soothing.
• Tea and honey
• Be patient it should be over in 2 weeks!

WHEN DO I NEED ANTIBIOTICS?
If you get a BACTERIAL infection

• The flu is caused by a virus, antibiotics (which work against bacteria) are not helpful. However, for some patients the flu virus can damage the lining of the respiratory tract and make it easier to get a bacterial infection. If you develop a bacterial infection then antibiotics may be needed to treat this secondary complication.

WHAT TYPES OF BACTERIAL INFECTION CAN I GET?
Sinusitis--infection of the sinuses

• Symptoms: severe pain and pressure in the affected sinus (see below), often with a bloody or thick green/yellow mucous. Note that even a simple "cold" virus can cause this same thick green/yellow mucous, however. Sinuses are air-filled cavities in the bones of the skull and are located in the center of the skull (sphenoid), behind the forehead (frontal bone), between the eyes (ethmoid), behind the cheeks (maxillary).

Otitis--infection of the inner ear

• Symptoms: intense pain, a feeling of fullness, decreased hearing, possibly dizziness because the balance part of the ear may also get inflamed The inner ear gets infected because the flu virus causes swelling of the throat around the small tube, called the Eustachian tube, that connects to the inner ear. When this drainage part is plugged, the virus can multiply without being washed out and this causes inflammation and production of fluid

Bronchitis-- infection of the bronchial tubes

• Symptoms: cough accompanied by thick green/yellow phlegm that may have blood in it if the patient has underlying chronic bronchitis OR if blood from sinus infection drains into the secretion Some patients with asthma may need to increase their bronchodilator medicines and some patients who don't usually have asthma may need these medications temporarily if the airways become too irritable and go into spasm.

Pneumonia infection of the lungs, also called pneumonitis.

• Note that the virus itself can cause a viral pneumonia. Symptoms of viral pneumonia: Very high fever, shortness of breath, sometimes chest pain, and a dry, irritating cough. The dry cough is the key. The chest x-ray may show a "hazy" pattern, not a specific spot Symptoms of bacterial pneumonia: Same high fever, shortness of breath, sometimes chest pain, and cough. The cough however, usually produces a thick green/yellow phlegm that may have blood, just like with bronchitis. The chest x-ray usually shows a specific area or areas of infection.

WHERE CAN I GET THE FLU SHOT?
Your family doctor or internal medicine doctor may have it. Dr Susan Vogel told me that her office just got their supply in! The Houston Public Health Clinics. Your grocery stores and pharmacies: Randalls, Kroger's, Eckerds, Walgreens, etc—watch for signs when you go there in the next few weeks Our office does not have the vaccine yet. We'll keep you posted. When it arrives, we will initially innoculate our patients who are receiving chemotherapy or radiation for metastatic (spread) cancer. We cannot give the vaccine to persons who are not our patients or who are not receiving chemotherapy because our supplies will be limited.

Let's hope we ALL escape the flu this season!

Last updated on Nov 9, 2008

• surgery to remove lymph nodes. Often, patients may have mild swelling in the arm in the first week or two after surgery because their surgeon doesn't want them to exercise until the drains have been removed. This is a temporary lymphedema and usually returns completely to normal. The lymphedema that develops 1 or more years after the surgery, is the kind we are discussing here.
• radiation treatment to the lymph node area (called "axilla")
• an infection in the arm, hands, or fingers
• vigorous and repetitive sudden movements with the arm, such as excessive scrubbing, polishing, raking, hammering, or exercise with the arm such as lifting weights.
• new tumor in the axilla
• injury--cuts, bruises, sun burn, insect bites, pet scratches, auto accident, vigorous cutting of cuticles or cutting finger nails too short, a "hard" massage such as Rolfing or Shiatsu or Acupressure
• lifting heavy objects
• constricting clothes, jewelry, handbags
• significant weight gain
• extreme and prolonged changes of temperature, for example, sauna, hot tub, Jacuzzi, whirlpool, heating pad or ice packs

In most patients, this is a gradual process that generally affects the forearm or upper arm. It can progress and affect the hand and fingers.

What can I do to prevent lymphedema?
As you might expect, if you minimize or eliminate the causes, you can minimize your chances of developing lymphedema. Some tips include:

• take good care of the skin on your arm, hands, and fingers. Keep it clean and moisturized with a moisturizer with a neutral or acid pH--such as nivea, Eucerin. Dry skin carefully but thoroughly, especially between the creases of the fingers. Take off your rings and make sure the skin under them and the rings are completely dry before putting them on again.
• use rubber gloves(if you are not allergic to rubber) when doing any cleaning that involves use of detergents or cleansing agents. Do not expose your skin to these chemicals.
• use rubber gloves if you wash dishes by hand and have your hands in water for a long period of time. The detergent and water may excessively dry your skin, making it crack and more susceptible to infection.
• avoid getting sun burned. Use a sun screen with the highest sun protection factor (SPF of 30, 40, 50) you can find. Note that a regular t-shirt only has a SPF of 3 or 4 so it alone is not sufficient.
• Food preparation: use a food processor or cutting board when chopping. Do not use your finger or thumb as the cutting board. Be VERY careful when shelling shrimp or crawfish or eating lobster.
• use an electric razor for shaving in the armpit (axilla). It is less likely to cut you than a straight razor.
• clean any cuts on your hand or arm immediately with soap and water and a mild antibacterial ointment (you can get it without a prescription).
• maintain your proper weight through good diet including fresh fruit and vegetables, and moderate exercise regularly (4 to 5 times a week).

AVOID smoking and excessive alcohol.

• if you have a large breast, do not buy a prosthesis for the mastectomy side that is too heavy. This will cause your bra strap to put too much weight on your collar bone and on the lymph channels beneath it. This will cause more back-up of lymph fluid.
• elevate your arm above your heart whenever possible. Put it on a pillow beside you at night. Don't sleep with your head on your arm.
• watch for any signs of infection: redness, especially in a streak or vein-type pattern, pain, warmth, swelling, blistering. If these occur, call me or your surgeon immediately for antibiotics that may require admission to the hospital.

What can I do if I already have lymphedema?
There are a number of possible treatments.
The goal is to shrink the lymphedema as much as possible and to prevent any more stretching of the lymph channels.

• lose excess weight
• see a physical therapist who can:

1. measure the amount of lymphedema
2. fit you for a "compression garment"--this is like a support stocking for the arm. The Jobst® stocking is the usual brand prescribed.
3. give you physical therapy with a compression pump (no longer approved by Medicare, unfortunately) or manual decongestive treatment--she gives a special massage to your arm and teaches you and/or your significant other how to do it for yourself.

• keep your arm elevated above your heart whenever possible
• be alert for any possible infections and treat them immediately.
• avoid a high salt diet

Can I take any medicine to shrink my arm? What about fluid pills?
Unfortunately, there are no pills that can "dry out" the arm. Fluid pills (diuretics) dry out the entire body, not just the arm. They may work temporarily, but are not a long term solution.

Last updated on Nov 9, 2008

• Health Insurance Portability and Privacy and Accountability Act
  

PAIN-Less is More! Myths about pain: Good for the soul Builds character Real (wo)men don't complain The truth about pain: IT HURTS Wears you down Makes everything else worse Keeps you from doing your stuff

• x-rays, blood tests, exams

 - Treat the cause, if possible

• change chemo or hormones
• radiation
• surgery

 - Use pain medicines

• Long acting
• Short acting

LONG ACTING Pain Medicine

• Sometimes called "Contin" for Continuous
• Lasts 8 to 12 hours
• Only have to take pills 2 or 3 times
• CONSTANT amount in blood
• Pain won't wake you up at night
• BUT-amount in blood is low enough so you won't feel sleepy

SHORT ACTING Pain Medicine

• Sometimes called "IR" for Immediate Release
• "Rescue"s you from pain that "Breaks Thru"
• Acts within minutes
• But doesn't hang around to make you sleepy

Goal of Pain Control

• Keep pain level 3 or less
• Need to take rescue medicines only once or twice a day

Other Notes

• Prevent constipation: Senokot-S _ tabs 2-3 times a day
• Drink 6-8 glasses of non-caffeine liquid daily
• Dry mouth: Artificial saliva liquid or spray

What does it do? How does it work? The cells in the body that need estrogen do their jobs have receptors for it called “estrogen receptors (clever, eh?)” or “ER” for short. Think of them as a “mouth” on the cell. (There may be MANY mouths or ERs on the cell. The more, the better!) Estrogen is made in 3 main places: 1) the ovaries, if you are premenopausal; 2) the placenta, if you are pregnant; 3) the fat (surprise!), if you are postmenopausal. Estrogen travels in the blood and when it passes cells with “ER”, the ER grabs it. The ER with Estrogen goes to the chromosomes where it acts as a “fertilizer” to make the cell grow. Remember how pregnancy causes the breasts to enlarge? The estrogen from the placenta was grabbed by the ER on the breast cells and 1 cell divided into 2 cells, 2 into 4, etc to prepare for making milk.

• To prevent breast cancer if higher than average risk; P1 Trial showed: 50% less, 70% if atypical ductal/ lobular hyperplasia
• To prevent cancer returning in women with IN SITU cancer that is sensitive to estrogen (“ER positive”)
• To prevent cancer recurrence in early stage (I, II, III) invasive (or “infiltra-ting”) breast cancer, ER positive. Early stage means the breast cancer was only in the breast or the nearby lymph nodes in the armpit (“axilla”), or under/above the collarbone.
• To treat breast cancer ER positive that has spread (“metastasized”); “stage IV.”

What is the dose of tamoxifen?
20 mg a day .
Tamoxifen is made in 2 pill strengths (20 mg and 10 mg) AND in a liquid form.

How long do you take tamoxifen?
For prevention (#1, 2, 3 above), 5 years.
For treatment (#4 above), as long as it works unless you have bad side effects.

Anything special about taking it? NO

1. Take it any time of day. If take it at night, may have less chance of nausea.
2. Can take with food or on empty stomach. BUT, usually less nausea if take with food.

What if I forget to take it?
Take it the next day to “catch up”. Take one in the morning and one at night. You need to try to keep the blood levels high enough to block the estrogen in your body from feeding the tumor.

What about side effects?
GOOD SIDE EFFECTS “benefits”

1. Prevent osteoporosis in postmenopausal
2. Lowers cholesterol

BACKGROUND
Why tamoxifen has GOOD side effects . Recall, tamoxifen “looks like” estrogen to the breast ER, but when it “docks” inside the ER, the shape of the molecule is different from estrogen so it clogs the ER and no estrogen can get in. Other cells in the body ALSO need estrogen such as: BONE cells, LIVER, UTERUS, VAGINA & URETHRA (the tube from the urinary bladder to the outside), SKIN, HAIR. The BONE and the LIVER ER are not as “picky” about the shape of tamoxifen as the breast cell ER is. BONE and LIVER cell ER can “fit” the tamoxifen molecule (kind of like fitting a triangle into a square hole), so it acts LIKE estrogen to strengthen bones strong & lower cholesterol. So, tamoxifen has GOOD (“estrogen-like”) effects .

What are the BAD side effects?
There are 2 typesof BAD side effects.

#1) NUISANCE Side Effects

• HOT FLASHES L . About 3 of 4 women have them. In 1 of 4 they are very mild, but in 1 in 4 they are severe. Two types of medicines are proven to safely decrease hot flashes. Both of these medicines have effects on “nerve” cells because that’s where the hot flashes begin è nerve cells in the brain that check estrogen levels in the blood.
1. EFFEXOR XR® (Venlafaxine)-an antidepressant that affects the ADRENALIN (excitement, pleasure) and SEROTONIN (satisfaction, comfort) brain chemical pathways . Dr Charles Loprinzi @ the Mayo Clinic showed Effexor XR will decrease hot flashes by HALF. Main side effects: headache, blood pressure may increase, constipation, slight decrease in sex drive; weight gain is less.
2. GABAPENTIN (Neurontin®) an anti-seizure and nerve healing medicine. (We often use this to help the nerves that have been injured during mastectomy or removal of lymph nodes in the armpit. These injured nerves cause a “burning, numb” pain on the upper inner arm and sometimes the chest wall.) Main side effects: sleepiness (so we take it at night).
3. OTHER MEDICINES carefully tested by Dr Loprinzi that DID NOT WORK are: BLACK COHOSH, CLONIDINE, VITAMIN E, BELLERGAL (also called Bellamin
• Vaginal discharge. About 3 of 4 women who still have a uterus, will have this. It may be white, clear, or pink colored. You may need a “light days” pad.
• Weight gain was NOT a side effect ! In the trial which compared tamoxifen to a placebo (“blank” pill), 70% of the women in BOTH groups gained weight. So, the women were EQUALLY LIKELY TO GAIN WEIGHT IF THEY TOOK A BLANK PILL AS IF THEY TOOK TAMOXIFEN! Sadly, most of us gain weight as we age because we are LESS ACTIVE. Ask about our dietician!

#2 DANGEROUS Side Effects

• Blood clots in deep veins. Overall, 1%. BUT, blood clots were more likely in persons with “risk factors” such as:
1. NOT ACTIVE. A bubbling brook doesn’t get algae on it. But if you dam it up and make it a pond, it gets scummy. In the same way, our blood will thicken and clot if we are confined to bed or sitting without getting up for long periods of time.
2. SURGERY. Surgery turns on the clotting system so you don’t bleed. If you plan surgery, stop tamoxifen 2 wks ahead. If you need emergency surgery, stop tamoxifen & tell your doctor you’ll need a blood thinner shot .
• Uterus cancer . If you have a uterus and are not having periods, tamoxifen acts like a weak estrogen and can cause a build up of the lining of the uterus which can become cancerous. This is more common in women who already have higher levels of estrogen (fat cells make estrogen, so it is HEAVIER women who are most at risk). So, you must 1) tell your gynecologist you are taking Tamoxifen; 2) have a pelvic exam once a year or sooner if you have abnormal vaginal bleeding. The risk of uterus ca is increased about 3X from 1 in 1500 to 1 in 500.
• Stroke. This is not very common. About 1 in 200 women had a stroke. There are 2 types of strokes: #1) “hemorrhagic” caused by bleeding; tamoxifen decreased this kind. #2) “ischemic” (due to clotting); tamoxifen increased this kind.

OTHER MINOR EFFECTS:

• Nausea. Usually mild. Resolves in a few wks.
• Emotional ups/downs; irritability. Like a “PMS”. Resolves in a few weeks.
• Cataracts may mature faster. Doesn’t cause them but they may grow faster. Wear UV blocking glasses and sunglasses to decrease! Get eye exam

HOT NEW INFORMATION 12-06 :

see “ Tamoxifen Activation” Info Sheet

1) Tamoxifen will not “work” until your CYP2D6enzymes CONVERT IT to Endoxifen. Most of us have normal 2D6 enzymes; but if they are mutated, Tamoxifen won’t block the ER. I will test your “cytochrome P450 2D6 gene type”.

2) Even if you have normal 2D6 enzymes, they can be completely blocked by some drugs. Two strong blockers are Paxil®, Prozac®. Zyban® (Wellbutrin®) is a moderate blocker. See others on list. Please don’t take any medicines or herbs that could block the 2D6 activation of Tamoxifen. Please bring a list of ANYTHING you take when we visit.

Dr Holmes & Janice

Tamoxifen metabolism (activation) by CYP 2D6
Tamoxifen must be activated to kill cancer

Research has shown that tamoxifen needs to be changed (activated) within the body to a much stronger form of the medication in order to be fully effective in the treatment of breast cancer. This process is called metabolism. An enzyme in the body (CYP2D6) is an important part of tamoxifen metabolism.
 

What is your CYP2D6 genotype? We all have different types of CYP2D6 genes - ort of like hair color. A simple blood test (CYP2D6 genotyping test) may help predict your body’s ability to change tamoxifen (a relatively inactive medication) to endoxifen (a form of

• Ultra rapid metabolizer. Your body will very effectively change tamoxifen to its most active form, endoxifen. You are likely to experience hot flashes when taking tamoxifen.
• Extensive (normal) metabolizer. Your body will likely change tamoxifen to its most active form, endoxifen. You are likely to experience hot flashes when taking tamoxifen.
• Intermediate metabolizer. Your body will likely be able to change tamoxifen into it’s active form, endoxifen at a slightly reduced rate compared to women with ultrarapid or extensive metabolism of the CYP2D6 enzyme. You may experience hot flashes when taking tamoxifen.
• Poor metabolizer. It is unlikely that your body will be able to convert tamoxifen into it’s most active form, endoxifen. If you are a poor metabolizer of CYP2D6 enzyme, your doctor may suggest a different treatment or drug to treat your breast cancer.

The CYP2D6 blood test is one factor that can be considered in determining the best treatment for you. However, even if your test result is normal, there other untested, undetected or unknown genetic changes which may affect the effectiveness of cancer treatments.

Other medicines can affect CYP2D6
Drugs can also affect the ability of the body to change tamoxifen to endoxifen

Women taking tamoxifen should use caution when taking other medications (both over-the counter and prescription drugs) that are known to prevent the ability of the body to change tamoxifen to endoxifen. The list below shows some medications that may interfere with activation of tamoxifen.

Bottom Line
Many factors help doctors determine if tamoxifen will be helpful for you. One important factor is to determine if your body has the right kind of CYP2D6 to ACTIVATE tamoxifen to the cancer killing form, ENDOXIFEN.

For this reason, I’d like to check your CYP2D6 blood test to see if tamoxifen is the best medication for your breast cancer

Medications that Inhibit the CYP2D6 Enzyme
Below are lists of medications that affect CYP2D6 enzyme activity. The medications are organized by category of their use, with brand and generic names noted.

This list doesn’t have ALL the medicines that can affect CYP2D6, BUT, they contain some of the common ones.They are based on information contained in published research to date. There may be medications that affect CYP2D6 enzymes, which are not listed below. With advances in pharmacogenetic research, additional medications may be added to these lists.

As you know, I ALWAYS want to see the list of ALL your medications when we visit. BUT, please let me (Dr Holmes) or Janice know about any new medicines you are prescribed if you are taking tamoxifen.

These medicines WEAKEN CYP2D6
So it can’t ACTIVATE Tamoxifen to ENDOXIFEN, the cancer killer. Let me know if you are taking any of them.

Antidepressants + Tranquilizers

• Fluoxetine Prozac®, Sarafem®, also a component of Symbyax™)
• Paroxetine Paxil®)
• Buproprion Wellbutrin
• Sertraline Zoloft
• Citalopram Celexa Not per
• Escitalopram Lexapro Dr Flockhart
• Duloxetine Cymbalta
• Perphenazine (Trilafon®, also found in Triavil® and Etrafon®)
• Thioridazine Mellaril®)
• Chlorpromazine Haloperidol
• Clomipramine Doxepin
• Perphenazine (Trilafon®,in T riavil® and Etrafon®)

Heart medicines

• Amiodarone
• Ticlopidine (Plavix) à BUT, not really a big enough effect to be important
• Quinidine (Cardioquin®, Quinaglute Dura-Tabs®, Quinidex Extentabs®, Quinora®, Biquin™*)

Arthritis medicines

• Celexoxib

Stomach medicines

• Cimetidine ( Tagamet®, Acid-eze™*); Rantidine

Allergy medicines

• Chlorpheniramine
• Azela stine (Astelin®, Aller-eze™*)
• Diphenhydramine (Benadryl)
• Clemastine
• Terbinafine
• Hydroxyzine

Other

• Desmethylazelastine* (a metabolite of azelastine)
• Dexmedetomidine (sedative delivered by infusion) (Precedex™)
• Pergolide (Permax®, Celance™*)
• Midodrine
• Moclobemide
• Perazine (Taxilan®*)
• Pergolide (Permax®, Celance™*)
• Pimozide (Orap®)
• Ritonavir
• Perazine (Taxilan®*)
• Pimozide (Orap®)
• Cocaine
• Halofantrine
• Levomepromazine
• Metoclopramide
• Methadone
• Mibefradi
• Midodrine
• Moclobemide
• Perazine (Taxilan®*)
• Pergolide (Permax®, Celance™*)
• Pimozide (Orap®)
• Ritonavir
  

Frankie Ann Holmes, MD, FACP Janice Tran, RN, NP-C 909 Frostwood Dr #221 Houston, TX 77024-2305 BREAST CANCER Telephone 713-467-1722 Direct Fax 713-343-0324 My dear Patient:  I’m sending you a copy of the results of the blood test we did at my office a few weeks ago when we discussed new information about TAMOXIFEN.  The test is called “Cytochrome P450 2D6 Genotype.”  It shows us what genes you inherited from your mother and father for the enzyme “2D6” BACKGROUND:  Genes Each of us inherits two sets of chromosomes:  one from MOM and one from DAD.  The information on each chromosome is stored in packages called “genes”.  Genes are what make us who we are.  For example, hair color, skin type, whether we are tall or short.  Some genes, like hair or skin color, come in many different “colors” or forms (so we call them polymorphisms.  “poly” means many and “morphism” means form.  Just like skin color, where, for example, albino skin is very sensitive to sunburn but the skin of blacks is much less sensitive. Remember that we discussed new information about how Tamoxifen kills cancer?  It is amazing that we have been using this medicine since the 1970’s but in 2003 scientists accidentally discovered how Tamoxifen REALLY works.  This was not very well publicized until about 2005, and even then, we still didn’t understand completely what it meant for our patients.  The new discoverey was that Tamoxifen isn’t the molecule that actually fights cancer!  Tamoxifen must be converted into ENDOXIFEN by the liver enzyme 2D6.  ENDOXIFEN is the real cancer kill drug. The next discovery was that we all have different “types” of the enzyme 2D6.  We call this “polymorphisms” (see box insert).  The NORMAL 2D6 enzyme is named  *1.  So, if you got 2 normal 2D6 enzymes from your MOM and DAD, then your genotype would be CYP 2D6 *1 / *1. There are 2 types of ABNORMAL 2D6 enzymes.  One type doesn’t work at all.  We call this “loss of function” or “null”.  Some of the NULL types are:  *3, *4, *5, *5, *6, *7.  The second type of 2D6 enzymes only work weakly.  We call them “dysfunctional”.  Some DYSFUNCTIONAL types are:  *9, *10, *17, *29, *41. There is one other rare group of people who actually have MORE THAN TWO COPIES OF 2D6 GENE.  They are called ULTRA-RAPID METABOLIZERS. We analyze each of the gene types and that tells us how effectively Tamoxifen will be converted by your body.  If you have the EXTENSIVE METABOLIZER type, then Tamoxifen should work great for you.  If you have the POOR METABOLIZER type, then it won’t work for you.  I will not prescribe tamoxifen.  If you are already taking it, we will discuss other options.  If you are INTERMEDIATE, tamoxifen will work but it may not be quite as effective.  BUT WE ARE STILL NOT SURE ABOUT that.  Scientists are still studying this.  For now, tamoxifen is reasonable, but it is IMPORTANT NOT TO TAKE ANY OTHER MEDICINES THAT COULD INACTIVATE your NORMAL 2D6 enzyme.  The list of those medicines is on the information sheet I already gave you.  Important ones to avoid FOR ALL PATIENTS, are Paxil, Prozac, Wellbutrin or Zyban. CLASSIFICATION:  How effective your body converts or METABOLIZES Tamoxifen to Endoxifen. NAME GENES EXAMPLE EXTENSIVE  2 normal  *1 / *1 INTERMEDIATE 1 normal & 1 abnormal *1 / *4 POOR   2 abnormal *4 / *4 ULTRARAPID more than 2 copies of the normal genes   I will continue to update you on developments in this area.  Being at the “cutting edge” for your care is key for me.  Dr Holmes         ________________________________________

• Fever,
• Chills, feeling cold
• Rarely nausea, muscle aches, back pain
• Even less common: allergic reaction with low blood pressure can drop and breathing can be blocked.

LATE REACTION

• More fevers and chills that can happen 12 to 24 hours later
• Weaking of the heart muscle that can happen after the patient has received many doses of Herceptin™ (12 or more)

Can you prevent these side effects?
We can prevent the immediate side effects very effectively by giving medication BEFORE the Herceptin™ which we call "Premedication." The premedication is:

• Tylenol 650 mg by pill
• Benadryl 25 mg IV

Right now, we don't have any way to prevent the possible LATE effects on the heart. However, we know that most patients with a healthy heart won't get the muscle weakening effect. So, the first thing we do is to check the heart. Often we can estimate heart function just by physical examination and a chest x-ray. However, the standard of care that has been developed is to do a heart scan before or just shortly after we start the Herceptin™ and then after every 12 or so doses of it.

The reason the heart muscle cell is affected is because it has a HER-4 protein (a cousin to HER-2) that sometimes picks up the Herceptin™. This makes the heart muscle cell weak. If a lot of cells are affected some patients will get congestive heart failure (shortness of breath, swelling of the ankles). Most of the time this happens because the patient has some other cause for weakening of the heart muscle and the Herceptin™ was "the straw that broke the camel's back". Some of the other conditions or causes of a weak heart muscle are: treatment with doxorubicin (Adriamycin), treatment with radiation to the left side of the chest wall, high blood pressure or diabetes.

What happens if patients get allergic symptoms anyway?

• We stop the infusion.
• Give more Benadryl IV
• If shaking chills develop, we give Demerol 25 to 50 mg IV
• If the reaction is severe, we give cortisone type medicine IV

Most of the time, however, the symptoms are very mild if at all and we can just slow the infusion down and give the Benadryl and patients are ok. Sometimes this "infusion" reaction of fever or chills can happen later during the night that they receive the Herceptin™. This is not dangerous. However, you should:

• Take Tylenol 650 mg pill
• Take Benadryl 25 mg pill
• Don't stay alone after your first treatment

Who should receive Herceptin™?
The current recommendations from the FDA (the Food and Drug Administration) is that patients who have more than normal amounts of HER-2 protein on their tumor cells and who have spread ("metastatic") breast cancer are possible candidates.

All of the testing with Herceptin™ showed that it was most effective in patients whose breast cancer tumors made too much HER-2 protein. If the breast cancer cell only made the normal amount of HER-2, it didn't seem to work at all. For this reason, we only give Herceptin™ to patients whose tumors have HER-2 protein.

How do you know if your tumor has HER-2 protein?
The tumor must be tested for HER-2. This test is done in two different ways.

• IHC-- stands for "Immuno Histo Chemical". This is done by putting an antibody (not Herceptin™) on the tumor and examining the cells to see if they took it up. This is the most common and cheapest test. It is the test that was done to figure out which patients to treat during the early research studies.
• FISH--- stands for "Fluorescent In Situ Hybridization". This test actually checks the tumor cell chromosomes to see if chromosome 17, that makes the HER-2 protein, is present in more than the usual number.
• The FISH method is about four times as expensive as the IHC test and requires a special microscope that most laboratories cannot afford. This test is usually sent out to be done.

The good news, however, is that either one of these tests can be done on the pieces of tumor from the slides from previous biopsies or surgeries. If those aren't available, a new area of tumor can be biopsied and tested. There is a blood test that can sometimes be done, but it isn't as reliable if it is negative.

How effective is Herceptin™ against breast cancer?
Given by itself, Herceptin™ caused shrinkage of tumor in about 15% of patients, that is about 1 in every 7 patients.

However, when Herceptin™ was combined with Taxol, it caused shrinkage in about 1 in every 2 or 3 patients.

How long can patients continue to receive Herceptin™?
We really don't know the answer to that question. The early studies treated most patients until it stopped working. Later studies used a specific amount of Herceptin™ and combined it with chemotherapy. These later studies found that combining Herceptin™ with Adriamycin (doxorubicin, the red chemotherapy) caused about 1 in 5 patients to have weakening of the heart muscle. However, when Herceptin™ was combined with Taxol, the number of patients who got weakening of the heart muscle was low.

Right now we will use the Herceptin™ as long as it seems to be working, for patients with spread (metastatic) breast cancer.

There are a few patients who are receiving Herceptin™ and who don't have tumor spread. Most of these patients have had very aggressive tumors that did not respond very well to chemotherapy given before surgery. These patients will receive Herceptin™ only for a specific number of treatments, usually 12 to 18.

Last updated on Nov 9, 2008

• Wellness Center Information - Memorial Hermann Hospital