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GIST Support International - Gleevec Side Effects and Tips
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As a wife and caregiver, I have tried to compile some general information and answers to frequently asked questions on side effects of Gleevec used for treatment of unresectable or metastatic Gastrointestinal Stromal Tumors (GIST). My husband was randomly assigned the 800 mg dose in the Phase III Gleevec trial in 02/2001 and remained on that dosage till 07/2004.

Imatinib mesylate was originally known as STI571 but is now sold by Novartis as ‘Gleevec’ in the United States and as ‘Glivec’ elsewhere. Gleevec is generally the first line of treatment for patients with unresectable and/or metastatic GIST. Gleevec is reported to show tumor shrinkage or stability in about 67% to 85% of GIST cases. About 60% of patients show some shrinkage of tumors during the first few months of taking Gleevec, but tumor symptoms can subside even if only stability is achieved. Hearing the word ‘stable’ on a scan is very good news! Charts indicate by the 3rd year mark, approximately 75% of GIST patients have had some incident of relapse, although this does not necessarily mean complete failure of the drug. These patients might switch to a higher dose, or have surgery to treat one rogue (resistant) tumor, and then successfully continue on Gleevec. We have GSI members who entered the Gleevec trials in 2000, assigned the 400 mg dose, and continue to have stability to date! .

Larger size tumors are hypothesized to increase chance of eventual resistance to the drug because of a greater chance of developing new secondary mutations. Recent reports state the 600 mg dose of Gleevec may be more advantageous and delay resistance for patients with a high baseline granulocyte count and when the tumor is in sites other than stomach or small intestines.

Gleevec is generally prescribed in 400 mg or 600 mg doses to be taken orally. Novartis instructions indicate that the 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. However, many oncologists recommend that patients split any dose if it helps to control side effects. Gleevec is only commercially available in 100-mg or 400-mg tablets (though early trials used capsules). Therefore, you could achieve a 600 mg daily dose by taking six 100-mg pills OR two 100-mg pills along with one 400-mg pill.

Though Gleevec was approved by FDA in 2002 for treatment of non-resectable and metastatic GIST after a lengthy trial process, additional clinical trials continue. Cancer research centers through the United States and the world participate in these closely monitored trials. "Adjuvant" studies are being conducted on hundreds of GIST patients whose tumors were resected, with the goal being to determine whether or not Gleevec can retard tumor recurrence. Other “neo-adjuvant” studies include the use of Gleevec to reduce the size of tumors pre-surgery in order to have greater success in totally resecting the tumor with clear margins.

For patients who become Gleevec-resistant, the first step is usually to increase their dosage to 600 or 800 mg, which has been reported to stabilize the tumors once again in about 1/3 of the cases. In the majority of these cases it has been reported that it usually only lasts a few months, however there are exceptions and GSI does have members that have reported continued stability after the increased dose. A high dose, such as 800 mg, does carry more risk of toxicities. Nonetheless, a higher dose should be considered if the lower dosage does not seem to work.

Gleevec may have interactions with other drugs such as birth control pills, Coumadin, Warfarin, St. John's Wort, erythromycin, phenytoin, or anticonvulsants. The same enzymes that metabolize Gleevec also metabolize these drugs. Therefore, drug interactions may occur. It is very important to tell your physician all your prescription and non-prescription drugs and to be sure your physician closely monitors for interactions or side effects when combining drugs.

Though liver problems are rare, a small percentage of GIST patients on Gleevec have experienced an intolerance to the drug, with liver enzymes rising to extremely high levels. In those cases, the patients are most likely taken off Gleevec, at least until enzymes return to normal. Also, through consultation with their oncologists and liver specialists, some of these patients have been given Prednisone, Immuran, or Entocort to stabilize their liver functions so that Gleevec could be successfully resumed.

The most common side effects of Gleevec are swelling around the eyes and legs as well as diarrhea, nausea, vomiting, muscle cramps, muscle or bone pain, abdominal pain, fatigue, excessive gas and rash. Many side effects are managed by other medications. In a small percentage of patients, Gleevec was reduced temporarily. In about 5% of cases the side effects were severe enough to discontinue the drug permanently.

Over 75% of GIST patients report fluid retention. It is important to report this to your physician, who should closely monitor and weigh you to prevent more serious complications including heart problems. You may be prescribed a diuretic, which removes water from the body by promoting urine formation and the loss of salt (sodium). Some patients prefer to take their diuretic early in the day so that don’t lose sleep at night running to the bathroom. Diuretics may rob the body of potassium, so often physicians prescribe a potassium supplement. (adding too much potassium to your diet may be harmful, so please only do this under a physician’s supervision). Patients taking diuretics should know what signs to look for if the diuretic depletes the body of too much potassium. Signs include fast or irregular heartbeat, weak pulse, nausea, vomiting, dry mouth (decreased saliva), excessive thirst, muscle cramps, mental and mood changes.

A few GSI GIST Patients have reported taking the prescription Protonix to help with nausea. Also Phenergan and Zofran have been reported to help. (Non-prescription suggestions include Coca-Cola, mashed potatoes, peaches and cream, toast, and Hershey's chocolate bars.) Many GSI members report that taking Gleevec with a meal or food greatly reduces nausea. Some patients have reported that out of medical necessity they needed to spread the Gleevec pills over the course of the day in order to avoid severe nausea and vomiting. This may be accomplished by having the tablet prescribed in 100-mg tablets instead of the 400-mg tablets.

Immodium and low-fiber food such as rice cereal has been reported by members to help against diarrhea.

Another side effect to check for is low blood counts. Some patients’ blood counts improved after temporarily stopping the drug (not advised unless out of medical necessity). Important: During treatment with Gleevec, you will need to have frequent blood tests to help your physician monitor your condition. These tests are for measuring your blood counts and checking your liver function. Blood counts should be performed weekly for the first month, biweekly the second, and every two to three months thereafter, being sure to check for liver problems.

Some GSI members have reported taking Quinine for Muscle Cramps, Benadryl for rash and Carafate for acid reflux.

GSI members also report thin skin that tears, bleeds, and bruises easily while on Gleevec. A general observation is that the higher the Gleevec dosage the more side effects including thinner skin. My husband took 800 mg of Gleevec for 42 months, from 02/2001 till 07/2004, as randomly assigned in the early trial protocol, and he had severely cracked toenails after the third year on Gleevec.

Hemorrhaging was reported in up to 19% of GIST patients in clinical trials. Most bleeds were in the gastrointestinal tract. Seek medical attention immediately if you suspect abnormal bleeding.

GIST patients also report headaches. Since acetaminophen is not recommended with Gleevec, patients should consult their pharmacist or physician regarding other options, such as ibuprophen.

Other GSI patients using Gleevec have reported being very cold and often bundle up in sweaters and extra blankets.

Gas. Many Gleevec users have reported having excessive gas that often carries a pungent odor. You might want to avoid eggs, broccoli, cabbage and cauliflower.

Other suggestions from our GSI members to help minimize Gleevec side effects :
some prefer to take their meds at bedtime or prior to a nap, and sleep off the Gleevec effects. Some have been told by their physician to stay in an upright position and not lie down till one hour has passed after taking Gleevec. (This was in one of the early clinical trial protocols).

Things to avoid while on Gleevec:

  • Too much sun.
  • Grapefruit juice.

Tylenol/Acetaminophen (Tylenol- -some GSI members have reported that they have on occasion taken Tylenol or a low dose of acetaminophen had been present in their pain pills. Only your doctor can recommend if they feel this may be safe in low doses for you).

Just as with any non-GIST individual, pain killers are sometimes needed for other problems. Some doctors allow the short-term use of Aleve. However, it is highly recommended that GIST patients closely monitor their fever and prevent any infections. Gleevec users may experience slower than normal healing as well as fever that is masked. Most physicians encourage reporting any significant elevation of fever so that the cause can be treated as quickly as possible.

By Katherine Flom

I compiled the above tips in hopes of having in one location some answers to the most frequently asked Gleevec questions as well as common Gleevec side effects. Material was gathered from the GSI archives, and from articles that I compiled from the websites listed below. Special thanks to Louise Ladd, Ginger Sawyer, and Julie Royster for their very valued input in helping me pull this together. I am a GIST caregiver with no medical training. My interest in closely studying Gleevec and its side-effects started in 01/2001 when my husband was diagnosed with a huge inoperable (unresectable) GIST tumor in the abdominal cavity wrapped around vital organs at age 49 and was only given a few short months to live. Thanks to the miracle drug Gleevec, (developed by Brian J. Druker, MD, and manufactured by Novartis) in a clinical trial, my wonderful and loving husband, Herb Flom, is thankfully still with us today.

(Note: Herb’s tumor grew Gleevec-resistant in July 2004, after 42 months of Gleevec, and he entered the SU11248 (sugen/Sutent) trial in September 2004 at City of Hope in Los Angeles, CA, where he has been stable for the past 14 months). Also a big note of thanks to a very bright PCP (primary care physician) Dr. Glen Sturhing of Woodinville, WA who first discovered the tumor when Herb complained of an upset stomach and also a big thanks to Herb’s initial Oncologist, Dr. Hank Kaplan, of Swedish Tumor Institute in Seattle who helped Herb get through the red tape and become the first patient in the Gleevec Phase III trial in the State of Washington on 02/08/2001. We feel the care and compassion of Dr. Kaplan was above and beyond the call of duty as he studied all he could in hopes of extending my husband’s life in a time when little was known or could be found on Gleevec, and the prognosis for GIST patients with large unresectable GIST tumors was very bleak.

Our experiences and information shared would not be possible if not for this GSI support group website which allows us to share our voyage and pass along our knowledge and laymen expertise as we walk the GIST journey together. http://www.gistsupport.org/

Additional recommended reading:

Effects of Imatinib (Gleevec) on GIST Cells
by Jonathan C. Trent, M.D. Ph.D.

What is the right dose of Gleevec?
By Margaret von Mehren, M.D., Fox Chase Cancer Center

Gleevec and Relapse Statistics
By George Demetri, M.D., Dana Farber Cancer Institute

Grading of Gastrointestinal Stromal Tumors (GISTs)
by Anette Duensing, M.D.

GIST and the LIVER
by Ronald P. DeMatteo, M.D., FACS

References used to help compile this article:

Journal of Clinical Oncology..
http://www.jco.org/cgi/content/abstract/23/24/5795?ct

Novartis
http://www.gleevec.com/info/page/gist  (Novartis, the maker of Gleevec, has a Patient Assistance Program (PAP) to help patients who may be eligible for financial assistance in covering the cost of the drug. The company has set up a Web site (www.Gleevec.com) as well as a toll-free number to call for more information about PAP or the drug itself: 1-877-GLEEVEC 1-877-453-3832).
http://www.pharma.us.novartis.com/novartis/pap/pap.jsp

Oregon Health & Science University
http://www.ohsu.edu/news/2003/060203gist.html

National Cancer Institute
http://www.cancer.gov

GSI
Gist Support International Archives
As of 10/30/05 GSI has 565 Subscribers including GISTers, caregivers, and friends sharing information and helping each other along the journey.
http://www.gistsupport.org/
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