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Old 07-17-2007, 11:45 AM   #1
tousled1
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Tykerb effectiveness increased by food

Article from Reuters:

By Julie Steenhuysen
CHICAGO (Reuters) - Taking advantage of the power of food to boost the effectiveness of drugs could sharply lower the cost of cancer treatments, U.S. researchers said on Monday.
"We can use drug interactions to our advantage," said Dr. Ezra Cohen, a cancer drug expert at the University of Chicago Cohen, whose work appears in the Journal of Clinical Oncology.
He and colleague Mark Ratain analyzed data from a recent clinical trial showing how food affected GlaxoSmithKline'snew breast cancer pill Tykerb, known generically as lapatinib.
The drug is supposed to be taken on an empty stomach. But taking it after a full meal would boost the amount of the drug circulating in the body by 167 percent, and taking it after a high-fat meal would boost it by 325 percent, the researchers found.
That might allow patients to use 40 percent less to achieve the same effect as taking it on an empty stomach. At a cost of $2,900 a month, the change could save each patient, or insurers, $1,740 or more a month, the researchers said.
And washing it down with grapefruit juice might allow patients to use as much as 80 percent less, they said. That could reduce the recommended dosage from the current five, 250 mg pills on an empty stomach to just one pill with a full meal and grapefruit juice chaser, they said.
But the researchers hastened to say they are not recommending that patients try this on their own.
"The first word of caution is 'do not try this at home.' The last thing we want is to have patients take their drug with food or change the dose on their own," Cohen said in a telephone interview. "That could be potentially dangerous."
The point, he said, is that instead of looking at drug interactions with food as something to be avoided, researchers should seek ways to benefit from them.
Food sometimes enhances the effectiveness of drugs because some foods are broken down by the same processes that the liver uses to break down drugs. If liver enzymes are all busy working on the food, they are not available to break down as much of the drug, meaning it circulates for longer in the system.
Cohen and Ratain are currently studying the effect of grapefruit juice, which is known to delay the breakdown of many drugs, on Wyeth's immune suppressant drug sirolimus or Rapamune, but there are many possibilities.
"The list can go on and on in terms of the agents that could be favorably modified to reduce dose and perhaps specific side effects," Cohen said.
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Stage IIIC Diagnosed Oct 25, 2005 (age 58)
ER/PR-, HER2+++, grade 3, Ploidy/DNA index: Aneuploid/1.61, S-phase: 24.2%
Neoadjunct chemo: 4 A/C; 4 Taxatore
Bilateral mastectomy June 8, 2006
14 of 26 nodes positive
Herceptin June 22, 2006 - April 20, 2007
Radiation (X35) July 24-September 11, 2006
BRCA1/BRCA2 negative
Stage IV lung mets July 13, 2007 - TCH
Single brain met - August 6, 2007 -CyberKnife
Oct 2007 - clear brain MRI and lung mets shrinking.
March 2008 lung met progression, brain still clear - begin Tykerb/Xeloda/Ixempra
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Old 07-17-2007, 12:18 PM   #2
Christine
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Tykerb = high fat meal works better/

Thanks for posting this valuable info from an article released today in th Jounal of Clinical Oncology. There is a teleconference today at 1pm from GSK on this very subject. I will be there, and prepared with this article in hand. Hugs, Christine
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Old 07-17-2007, 01:45 PM   #3
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GSK does not recommend following the advice given in this article. They will issue a formal response shortly.

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Old 07-30-2007, 12:35 PM   #4
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GSK's Rebuttal of Article

Click on the link:

http://her2support.org/temp/gsk11.pdf


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Old 07-30-2007, 06:37 PM   #5
Heide
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Good to know!

I start the Tykerb/Xeloda combination within the next 10 days or so and will be taking it as instructed by my oncologist - without food. Thanks for the info!
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DX at age 37 on 5/24/05 Left breast IDC and DCIS, high-grade
modified radical skin-sparing mastectomy 7/11/05 with re-con TRAM flap.
tumor size 3.5 cm
HER2 To CEP-17 Ratio = 6.76 positive ER positive
A & C infusions Aug. - Oct. 2005
Taxol & Herceptin infusions Oct. - Dec. 2005
6 weeks radiation completed March 2006
Continued on Herceptin every 3 weeks until 10/24/06
re-occurence left side supraclavicular nodes Jan. 2007
HKI-272 phase 2 Trial Jan. - July 2007 (supra nodes shrunk for awhile)
Enlarged node in chest wall near windpipe.
started Tykerb/Xeloda 8/22/07 (on for 2 months - not working - 3 new liver mets).
11/07 Neupogen(G-CSF)/Herceptin/Navelbine Trial 11/07
2/8/08 Catscan shows 1 of 3 liver mets went from 9 to 24mm.
2/29/08 Phase II trial of Ertumaxomab.
4/10/08 Catscan shows progression on liver mets and 2 new liver mets.
4/11/08 Started Taxotere/Herceptin.
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Old 07-30-2007, 11:33 PM   #6
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I asked my onc about this last week and he said that even though it may sound promising, don't ever try your own dosing at home or it could cause increased side effects.
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NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)

Nov'03~ dX stage 2B
Dec'03~
Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~
Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~
micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~
micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg

Apr'07~
MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~
Started Tykerb/Xeloda, no WBR for now
June'07~
MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~
MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~
PET/CT & MRI show NED
Apr'08~
scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~
MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~
dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~
Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~
new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~
new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~
25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.

"I would rather be anecdotally alive than statistically dead."
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Old 07-31-2007, 03:09 PM   #7
Lolly
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Thanks Joe! I called Tykerb yesterday to see if they could send me the response since I couldn't find it on their web site, and they said it would be out in next month's JCO. Should of checked here first, as you and Christine are as always one step ahead!

<3 Lolly
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Sept.'99 - Dx.Stage IIIB, IDC ER/PR-, HER2+++ by IHC, confirmed '04 by FISH. Left MRM, AC x's 4, Taxol x's 4, 33 Rads, finishing Tx May 2000. Jan.'01 - local/regional recurrence, Stage IV. Herceptin/Navelbine weekly till NED August 2001, then maintenance Herceptin. Right Mast. April 2002. Local/Regional recurrence April '04, Herceptin plus/minus chemo until May '07. Gemzar added from Feb.'07-April '07; Tykerb/Abraxane until August '07, back on Herceptin plus Taxotere and Xeloda Sept. '07. Stopped T/X Nov. '07, stopped Herceptin Dec. '07, started Avastin/Taxol/Carboplatin Dec. '07. Progression in chest skin, stopped TAC March '03, started radiation.

Herceptin has served as the "Backbone" of my treatment strategy for over 6 years, giving me great quality of life. In 2005, I was privileged to participate in the University of Washington/Seattle HER2 Vaccine Trial.
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