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= Ma= naging Gleevec Side Effects
Presented by:  The Life Raft Group
February 8, 2006=
Special thanks to Jonathan Trent, M.D., Ph.D., Department of Sarcoma, MD Anderson Cancer Center, for his h= elpful comments. 
(Dr. Trents’ personal observations are noted in b= lue)
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Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Managing Gleevec Side Effects
Gleevec Side Effects
nDespite publicity to the contrary, Gleevec can have significant side effects
nBut side effects do tend to get better over time
= 226;Could be related to the theory of Gleevec drug levels falling over time (levels can decrease 40% over 12 months)
nBeing able to manage Gleevec side effects is a key step that allows patie= nts to take their Gleevec as prescribed
------=_NextPart_01C632BC.5450F4F0 Content-Location: file:///C:/12941AF3/gleevec_managing_side_effects_files/master04_image004.gif Content-Transfer-Encoding: base64 Content-Type: image/gif R0lGODdhFgKQAXcAACH+GlNvZnR3YXJlOiBNaWNyb3NvZnQgT2ZmaWNlACwAAAAAFgKQAYD///8B AgMC/4SPqcvtD6OctNqLs968+w+G4kiW5omm6sq27gvH8kzX9o3n+s73/g8MCofEovGITCqXzKbz CY1Kp9Sq9YrNarfcrvcLDovH5LL5jE6r1+y2+w2Py+f0uv2Oz+v3/L7/DxgoOEhYaHiImKi4yNjo +AgZKTlJWWl5iZmpucnZ6fkJGio6SlpqeoqaqrrK2ur6ChsrO0tba3uLm6u7y9vr+wscLDxMXGx8 jJysvMzc7PwMHS09TV1tfY2drb3N3e39DR4uPk5ebn6Onq6+zt7u/g4fLz9PX29/j5+vv8/f7/8P MKDAgQQLGjyIMKHChQwbOnwIMaLEiRQrWryIMaPGjf8cO3r8CDKkyJEkS5o8iTKlypUsW7p8CTOm zJk0a9q8iTOnzp08e/r8CTSo0KFEixo9ijSp0qVMmzp9CjWq1KlUq1q9ijWr1q1cu3r9Cjas2LFk y5o9izat2rVs27p9Czeu3Ll069q9izev3r18+/r9Cziw4MGECxs+jDix4sWMGzt+DDmy5MmUK1u+ jDmz5s2cO3v+DDq06NGkS5s+jTq16tWsW7t+DTu27Nm0a9u+jTu37t28e/v+DTy48OHEixs/jjy5 8uXMmzt/Dj269OnUq1u/jj279u3cu3v/Dj68+PHky5s/jz69+vXs27t/Dz++/Pn069u/jz+//v38 +/u7/w9ggAIOSGCBBh6IYIIKLshggw4+CGGEEk5IYYUWXohhhhpuyGGHHn4IYogijkhiiSaeiGKK Kq7IYosuvghjjDLOSGONNt6IY4467shjjz7+CGSQQg5JZJFGHolkkkouyWSTTj4JZZRSTklllVZe iWWWWm7JZZdefglmmGKOSWaZZp6JZppqrslmm26+CWeccs5JZ5123olnnnruyWeffv4JaKCCDkpo oYYeimiiii7KaKOOPgpppEkUAAA7 ------=_NextPart_01C632BC.5450F4F0 Content-Location: file:///C:/12941AF3/gleevec_managing_side_effects_files/slide0025.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Managing Gleevec Side Effects
Patient/Doctor Communications
nIt is important for patients to report side effects and discuss their management with their doctor
nThe material presented here is for information purposes only
&= #8226;It is not a substitute for talking to your doctor
•
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Common Side Effects
<= span style=3D'font-size:117%'>nFatigue
<= span style=3D'font-size:117%'>nAnemia
<= span style=3D'font-size:117%'>nNausea or vomitin= g
<= span style=3D'font-size:117%'>nDiarrhea
<= span style=3D'font-size:117%'>nEdema/fluid retention
<= span style=3D'font-size:117%'>nCramps
<= span style=3D'font-size:117%;visibility:hidden'>n&#= 13;
<= span style=3D'font-size:117%;visibility:hidden'>n&#= 13;
<= span style=3D'font-size:117%;visibility:hidden'>n
nRash/skin problems
nJoint pain
nEyes
•Itchy, watery eyes
•= Bleeding (less often)
nSensitive to sunlight
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Less Common Side Effects
<= span class=3DBB style=3D'position:absolute;left:-4.52%;top:.22em'>nBleed= ing
<= span class=3DBB style=3D'position:absolute;left:-3.79%;top:.22em'>nEleva= ted liver function tests (detected= on a blood test)
<= span class=3DBB style=3D'position:absolute;left:-4.52%;top:.22em'>nKidney problems
<= span class=3DBB style=3D'position:absolute;left:-4.52%;top:.22em'>nSerio= us edema (fluid retention)
nHemat= ological (blood counts) including neutropenia (low neutrophil counts)&#= 13;
<= span class=3DBB style=3D'position:absolute;left:-4.52%;top:.22em'>nHypot= hyroidism (low thyroid function)
<= span style=3D'visibility:hidden'>n
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Dose-related side effects
nEdema
nFatigue
nAnemia
nRash
•-= however female gender may be a higher risk factor
nBleeding
nNausea
nDiarrhea
nHematological effects (effects on blood counts)= 3;
n= These are worse in patients started at 800mg compared to patients started at 400mg.  Starting at 400mg for 4 weeks then increasing to 800 mg may help patients tolerate the higher dose. It does in my experience and is supported by a study at ASCO (Dileo et al, ASCO 2= 005)
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Fatigue/anemia-the number 1 complain= t
nKIT signaling is important to the formation of blood cells, including red blood cells
•Suppressio= n of normal blood cell formation is estimated to be minor, in the range of 10% to 20%
nSutent= may suppress blood counts more as it also inhibits FLT-3, another important growth factor for blood cells
nAnemia can be caused by:
•B= leeding (which can be undetected)
•<= span style=3D'font-size:83%;color:#0000CC'>Iron deficiency and B12 deficiency- = both common in patients who have had stomach surgery. These can all be tested for by a doctor.
nSome report fatigue a few hours after taking Gleevec
n
Counts= of Sutent patients may recover during “off-drug” periods.
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Growth Factors affecting Hematopoiesis
AMGEN®
KIT si= gnaling occurs when KIT is activated by Stem-cell factor (SCF). Gleevec inhibits this pathway
FLT-3 = is also involved in many branches of blood cell formation. Because Sutent inhibits KIT and FLT-3, it may be a more potent suppressor of blood counts.=
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