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05-19-2012, 05:14 PM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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new brain tumor treatment ? for mets, too if proves itself
2069 General Poster Session (Board #15H), Sat, 1:15 PM-5:15 PM
Effect of electrochemotherapy with IV bleomycin on complete response in a preclinical brain tumor study.
Birgit Agerholm-Larsen, Helle K. Iversen, Jakob M. Moller, Per Ibsen, Kurt S. Jensen, Mette Linnert, Julie Gehl; Department of Oncology, C*EDGE at Glostrup Research Institue, Glostrup, Denmark; Department of Neurology, C*EDGE at Glostrup Research Institute, Copenhagen University Hospital Glostrup, Glostrup, Denmark; Department of Radiology, Copenhagen University Hospital Herlev, Herlev, Denmark; Department of Pathology, Copenhagen University Hospitals Herlev and Hvidovre, Hvidovre, Denmark; Department of Oncology, C*EDGE at Glostrup Research Institute, Glostrup, Denmark; Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark
Background: Electrochemotherapy (ECT) describes enhanced chemotherapeutic drug uptake after cell membranes have been made transiently permeable due to application of an electric field to the tumor. ECT is routinely used to treat skin metastases, with high response rates after once-only treatment. We have developed an electrode for use in the brain, both a rodent model and an electrode for clinical use. The aim of the present study was to evaluate ECT using intravenous (iv) bleomycin in a rat brain tumor model. Methods: Sprague Dawley male rats (7-11 week old) were inoculated with rat glial cell derived tumor cells (N32) through a burr hole in the skull. When tumors appeared on MRI, animals were allocated to ECT (iv bleomycin and local electric pulses), iv bleomycin only, iv bleomycin with placement of electrodes (no pulses), or no treatment. Bleomycin was injected iv in the tail vein (600L, 3 IU/L) and electrode deployment was made through the burr hole into the brain tissue. Electrochemotherapy parameters were 32 pulses, 100V, 100s, 1Hz. Tumor size was determined based on contrast enhanced area from MR scans. Kaplan-Meyer events were defined as termination due to extensive tumor progression prior to end of the three independent experiments performed. Immuno-histo-pathology was performed after termination to verify MRI findings. Results: In 88% of the animals (14 of 16) treated with electrochemotherapy we found complete response (no tumor), validated by MRI and immuno-histo-pathology, whereas bleomycin only, bleomycin and electrodes, and no treatment showed progression in 11 out of 13 control animals. A Kaplan-Meier plot showed a pronounced improved survival for the ECT group as compared to controls within 3 weeks from treatment (p0.001). Treatment was well tolerated. Conclusions: The present data suggest that electrochemotherapy with iv injection of bleomycin is a new promising treatment for brain tumors. In a clinical study using iv bleomycin and electrochemotherapy for brain metastases ( www.clini- caltrials.gov, ID:NCT01322100) the first patient has just been treated successfully with ECT, indicating feasibility of the approach in the clinical setting.
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05-20-2012, 10:38 PM
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#2
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Senior Member
Join Date: Oct 2005
Posts: 3,519
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Re: new brain tumor treatment ? for mets, too if proves itself
Is the clinical trial so far only available at hospital in Copenhagen? I don't need it right now, but curious...
__________________
Brenda
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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05-21-2012, 12:10 PM
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#4
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Senior Member
Join Date: Sep 2005
Location: Central Coast, CA
Posts: 3,207
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Re: new brain tumor treatment ? for mets, too if proves itself
Brenda, I know you...just looking for an excuse to go to Copenhagen, right?
Sounds promising tho!
__________________
Chris in Scotts Valley
June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?"
9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response!
04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver
02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1
02/09 Continue NED
02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
07/11 - 11/11 Herceptin/Xeloda -not working:(
12/11 Begin MM302 Phase I trial - bust:(
03/12 3rd times the charm? AKT trial
5/12 Scan shows reduction! 7/12 More reduction!!!!
8/12 Whoops...progression...trying for Perjeta/Herceptin (plus some more nasty chemo!)
9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
11/12 Navelbine/Herce[ptin - try for a 3 cycles, no go.
2/13 Gemzar/Carbo/Herceptin - no go.
3/13 TACE procedure
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