Been invited to join Lapatnib trial - should I?

I've been wondering about Lapatnib as well looked up side effects and info on this here is what I found. 

Lapatinib

Lapatinib 

(la-PA-ti-nib)

Trade name: TYKERB®

Chemocare.com uses generic names in all descriptions of drugs. TYKERB is the trade name for lapatinib. In some cases, health care professionals may use the trade name TYKERB when referring to the generic drug name lapatinib.

Drug type: Lapatinib is a targeted therapy.  Lapatinib is classified as a signal transduction inhibitor - tyrosine kinase inhibitor, inhibitor of EGFR and HER2. (For more detail, see "How this drug works" below).

What lapatinib is used for:

• Treatment of patients with advanced or metastatic breast cancer that is HER-2 positive, and have already had certain other breast cancer treatments.   (It is approved for this use in combination with the chemotherapy medication capecitabine)

Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How lapatinib is given:

• Lapitinib is a tablet to be taken by mouth.
• Tablets come in 1 dosage size, 250mg.
• Take lapitinib exactly as instructed by your doctor. 
• Lapitinib should be taken at least on hour before, or at least one hour after food (take total dose at the same time daily, dividing doses is not recommended).
• Do not eat or drink grapefruit products while taking lapatinib.
• If you miss a dose of lapitinib, take it as soon as you remember that day.  If you miss a day, do not double your dose the next day.  Just skip the missed dose.  Call your healthcare provider if you are not sure what to do.
• Your doctor may adjust your dose of lapatinib depending on how you tolerate the treatment.
• Store lapatinib tablets at room temperature between 59^o and 86^o (15^o to 30^oC).  Keep the container closed tightly, and out of the reach of children. 

Side effects of lapatinib:

Important things to remember about the side effects of lapatinib:

• You will not get all of the side effects mentioned below.
• Side effects are often predictable in terms of their onset, duration, and severity.
• Side effects are almost always reversible and will go away after therapy is complete.
• Side effects are quite manageable. There are many options to minimize or prevent them.

The following side effects are common (occurring in greater than 30%) for patients taking lapatinib in combination with capecitabine:

• Diarrhea 
• Hand-foot syndrome (Palmar-plantar erythrodysesthesia or PPE) -skin rash, swelling, redness, pain and/or peeling of the skin on the palms of hands and soles of feet.  Usually mild, has started as early as 2 weeks after start of treatment.  May require reductions in the dose of the medication. 
• Low red blood cell count (anemia) 
• Nausea and vomiting.
• Elevated liver enzymes (increased AST, ALT, and bilirubin levels).

These are less common side effects for patients receiving lapatinib in combination with capecitabine:

• Rash
• Low blood counts. Your white blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, and/or bleeding.
• Fatigue, tiredness
• Abdominal pain 
• Mouth sores  
• Heartburn
• Pain in arms, legs, back 
• Shortness of breath
• Difficulty sleeping 
• Dry skin

These are rare but serious side effects of lapatinib.

• Heart problems including decreased pumping of blood from the heart, or abnormal heartbeat can occur rarely. 
• Severe diarrhea, which may lead to dehydration.

This list includes common and less common, and severe side effects for those taking lapatinib. Side effects that are very rare -- occurring in less than about 10 percent of patients -- are not listed here. But you should always inform your health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100.5º F (38º C) or higher, chills (possible signs of infection)
• Palpitations or are short of breath.

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Diarrhea (4-6 episodes in a 24-hour period).
• Nausea (interferes with ability to eat and unrelieved with prescribed medication).
• Vomiting (vomiting more than 4-5 times in a 24 hour period).
• Tingling or burning, redness, swelling of the palms of the hands or soles of feet.
• Unusual bleeding or bruising
• Black or tarry stools, or blood in your stools.
• Blood in the urine.
• Extreme fatigue (unable to carry on self-care activities).
• Mouth sores (painful redness, swelling or ulcers).
• Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decrease amount of urine, or dizziness.

Always inform your health care provider if you experience any unusual symptoms.

Precautions:

• Before starting lapatinib treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, products containing aspirin unless your doctor specifically permits this.
• Lapatinib interacts with many common medications.  Be sure to notify your doctor before starting any new medications.
• Do not receive any kind of immunization or vaccination without your doctor's approval while taking lapatinib.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (lapatinib may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus.)
• For both men and women: Use contraceptives, and do not conceive a child (get pregnant) while taking lapatinib. Barrier methods of contraception, such as condoms, are recommended.
• Do not breast feed while taking this medication.

Self-care tips:

• Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• Follow regimen of anti-diarrhea medication as prescribed by your health care professional. 
• Eat foods that may help reduce diarrhea (for more information see -  managing side effects - diarrhea).
• Prevention of hand-foot syndrome. Modification of normal activities of daily living to reduce friction and heat exposure to hands and feet, as much as possible during treatment with lapatinib. (for more information see - managing side effects: hand foot syndrome).
• Keep palms of hands and soles of feet moist using emollients such as Aveeno^®, Udder cream, Lubriderm^® or Bag Balm^®. 
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
• To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed with 8 ounces of water.
• You may be at risk of infection report fever or any other signs of infection immediately to your health care provider.
• Wash your hands often.
• Use an electric razor and a soft toothbrush to minimize bleeding.
• Avoid contact sports or activities that could cause injury. 
• Avoid sun exposure.  Wear SPF 15 (or higher) sunblock and protective clothing.
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely.  You should discuss this with your doctor.
• Get plenty of rest. 
• Maintain good nutrition.
• If you experience symptoms or side effects, be sure to discuss them with your health care team.  They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and testing:

You will be checked regularly by your doctor while you are taking lapatinib, to monitor side effects and check your response to therapy. Periodic blood work will be obtained to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.

How lapatinib 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 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. 

Lapatinib belongs to the signal transduction inhibitor category of targeted therapies.  It particularly interferes with the protein-tyrosine kinases; Epidermal Growth Factor Receptor (EGFR[ErbB1]) and of Human Epidermal Receptor type 2 (HER2 [ErbB2]).

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

I'm just curious. When I asked my Onc about Tykerb, I was told they only give it to Stage IV metastatic patients.

There is a current clinical trial where they are giving Tykerb in conjunctin with Herceptin for earlier stage patients.  I believe they are tracking effects on reoccurance.  I am not certain what the exact qualifications are to participate.  Ask you onc to reserach the clinical trial and see if you qualify.   My onc started me on it a couple months after I finished up my  Taxotere and Carboplatin.   So I get Tykerb and Herceptin together.   For me, it is totally tolerable. 

Jennifer

Hi Lucy,

I'd go for it! I think it's a good opportunity and it certainly won't do you any harm.  Like you said, Lapatinib crosses the brain barrier, which H. doesn't.  I suspect in the future they will figure out that L + H is the course of treatment which works best for us HER 2+ girls.  I think your strategy of pulling out in future if you feel you need to, is a good one.  Let us know how it goes.

Lisa 

I believe this is the trial I was asked to participate in.The only reason I did not, was because of the AC and the heart problems associated with it in conjuction with herceptin.My onc felt there was less risk of heart trouble with the TCH. Jackie

Thanks to krcll who bumped this thread. 

I am in this lapatinib trial. I got assigned to the arm that receives lapatinib starting Aug 28. until I have my surgery, which I expect to be last week of December 09 or first week of January 2010.  I take 1250 mg of lapatinib daily.  I first did 4tx of AC and now am ready to start my 2nd of 4 cycles of Taxol.  I started the Taxol and lapatinib the same day.  After surgery I will switch to weekly Herceptin.

The first two weeks of lapatinib I had no SE. Since then I had diarrhea for about a week until I got the Imodium dose balanced between diarrhea and constipation.  I do get the tiniest bit of upset stomach after taking the lapatinib that I attributed to having to gulp down 5 large pills at once on an empty stomach and not being able to eat anything until 1 hour after taking the pills.

In the study I'm in there is no arm that allows for lapatinib only.  From the write up I read about the study, one of the reasons for trying lapatinib in early stage is that the cells can build a tolerance or resistance to Herceptin, but not so with lapatinib.  

I did not see any (longterm) downside to joining the study. Lapatinib works on HER2+, proven, so I am not lacking any treatment. The study will benefit future HER2+ ladies.  Since I got in the arm that is lapatinib pills first, the Friday I don't have a Taxol tx, is a Friday I don't have to go to the hospital, which gives me a two week break from being there. Another benefit is the lapatinib pills and tests are paid for by the study, which gives me a little bit of a financial break.  

Brenda26- Thanks so much for sharing your experiences! It makes me feel better about the Lapatinib alone arm. It is wonderful that it worked SO well for you!

YES....I was in a clinical trial that involved Lapatnib before I had my masectomy and am currently going thru TCH. My trial involved early stage use of Lapatnib with Abraxane. I responded quite well. My tumors both shrunk down. They were both 2cm. One shrunk down to about 1 cm and the other was hardly there anymore. The doctors were very happy. They told me the advantage of doing the Lapatnib was that you get a more advanced for of Herceptin at an earlier stage....as Lapatnib is usually given only to later stage cancers.....so why wouldnt I want to take advantage of that......plus...with a trial you still have to do the regular course of treatment, so I am now doing the Herceptin. I did get a horrible rash from the Laptnib, but dermitologist gave me something and it went away....other than that....just the usual dierreha and constipation dance.