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06-14-2011, 12:34 PM
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#1
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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Saracatinib and herceptin
Hi
Have just been reading some research done at M D Anderson about a new targeted drug, saracatinib which when combined with herceptin seems to be able to very effectively overcome herceptin resistence.
I have done a search as the article implied it could soon be in clinical trials for bc but couldn't find any more information.At present there are trials for other types of cancer using this drug.
As it has a good safety profile and less side effects I thought it was a good option for those struggling with recurrence.
Anyone got any more information?
Ellie
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06-14-2011, 02:51 PM
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#2
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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Re: Saracatinib and herceptin
The ever expanding palette of mibs and nibs...
Maybe folks with links to Dr. Slamon could ask him.
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06-14-2011, 03:26 PM
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#3
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Senior Member
Join Date: Oct 2005
Posts: 3,519
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Re: Saracatinib and herceptin
Very interesting... we should be able to scare something up...
__________________
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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06-14-2011, 03:36 PM
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#4
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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Re: Saracatinib and herceptin
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06-14-2011, 09:53 PM
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#5
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Senior Member
Join Date: Oct 2007
Posts: 1,851
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Re: Saracatinib and herceptin
Here's something from ASCO. Although I was there, I did not see this but just searched for it. Breast cancer is mentioned, but not Herceptin.
The potential of circulating microRNA (miRNA) levels as a biomarker in drug development: An analysis of tumor-serum samples from patients on a phase I trial of saracatinib-paclitaxel (P)-carboplatin (C).
Sub-category: Prognostic Factors
Category: Tumor Biology
Meeting: 2011 ASCO Annual Meeting
Session Type and Session Title: General Poster Session, Tumor Biology
Abstract No: 10548
Citation: J Clin Oncol 29: 2011 (suppl; abstr 10548)
Author(s): D. S. Tan, S. Aamdal, G. Freyer, R. J. Jones, S. B. Kaye, E. Pujade-Lauraine, J. Fog, M. Wrang Teilum, C. Glue, A. Baker, U. A. Emeribe, P. Elvin, C. Stephens, M. Stuart, J. Walker, E. Boven
Abstract:
Background: miRNAs are small non-coding RNAs of 20-25 nucleotides with diverse regulatory functions including proliferation, cell differentiation and apoptosis. Unlike mRNA, miRNAs are stable in circulation, potentially offering valuable insights to pharmacologic modulation of drug targets and cell physiology, overcoming some of the challenges associated with tumor biopsies. We explored circulating miRNAs as a biomarker in the Phase I trial of saracatinib (AZD0530) in combination with standard doses of P and/or C (NCT00496028). Methods: Formalin fixed paraffin embedded (FFPE) tumor (n=29) and serum samples (n=69; 22/69 paired pre- and post-treatment) were profiled using Exiqon LNA based QPCR system (n=730 miRNAs) to analyze miRNA expression. Tumor samples analyzed included colorectal (CRC; n=8), ovary (7), pancreas (3), breast (2), esophagus (3), bladder (2), bone, lung, prostate, stomach (1 each). Results: Pre-analytical quality control revealed 28/29 tumor and 55/69 serum samples suitable for miRNA assessment. Unsupervised clustering of miRNAs derived from FFPE samples revealed discriminatory potential to identify the tissue of origin. Importantly, while distinct miRNA profiles were associated with certain tumor types, only selected miRNAs were concordant in matched tumor-serum samples, eg high miR192 and miR194 in CRC. We further examined specific miRNAs that may function as surrogate markers of Src kinase activity, eg miR194 (Li et al. Oncogene 2009;28:4272–83). Although there was no significant change in miR194 levels in 22 paired serum samples, when we excluded CRC patients which typically have high miR194 levels, significant increase in miR194 was seen post exposure to treatment (n=14, P=0.037). Conclusions: Circulating miRNA profiles can be reliably and reproducibly measured in serum, with some degree of tumor-serum concordance. Validation of miRNAs regulated by drug-targeted pathways should consider tumor-of-origin artifacts; adoption of a ‘miRNA profile’ may circumvent this concern. The role of circulating miRNAs as a biomarker in clinical trials warrants further evaluation.
Associated Presentation(s):
1. The potential of circulating microRNA (miRNA) levels as a biomarker in drug development: An analysis of tumor-serum samples from patients on a phase I trial of saracatinib-paclitaxel (P)-carboplatin (C).
Meeting: 2011 ASCO Annual Meeting
Presenter: Daniel Shao-Weng Tan
Session: Tumor Biology (General Poster Session)
__________________
Diagnosed stage 2b in July 2003 (2.3 cm, HER2+, ER-/PR-, 7+ nodes). Treated with mastectomy (with immediate DIEP flap reconstruction), AC + T/Herceptin (off label). Cancer advanced to lung in Jan. 2007 (1 cm nodule). Started Herceptin every 3 weeks. Lung wedge resection April 2007. Cancer recurred in lung April 2008. RFA of lung in August 2008. 2nd annual brain MRI in Oct. 2008 discovered 2.6 cm cystic tumor in left frontal lobe. Craniotomy Oct. 2008 (ER-/PR-/HER2-) followed by targeted radiation (IMRT). Coughing up blood Feb. 2009. Thoractomy July 2009 to cut out fungal ball of common soil fungus (aspergillus) that grew in the RFA cavity (most likely inhaled while gardening). No cancer, only fungus. Removal of tiny melanoma from upper left arm, plus sentinel lymph node biopsy in Feb. 2016. Guardant Health liquid biopsy in Feb. 2016 showed mutations in 4 subtypes of TP53. Repeat of Guardant Health biopsy in Jana. 2021 showed 3 TP53 mutations, BRCA1 mutation and CHEK2 mutation. Invitae genetic testing showed negative for all of these. Living with MBC since 2007. Stopped Herceptin Hylecta (injection) treatment in March 2020. Recent 2021 annual CT of chest, abdomen and pelvis and annual brain MRI showed NED. Praying for NED forever!!
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