~Too Many Brain Mets To Count~Mighty Oak's Saga Continues...

[pattyz]

Marie... can I say more than just 'hell' here??? Pretend I did, ok.

I can't think of what I sent that must be written off if it was not tried?

My onc wants to go right to Irinotecan w/my Temodar. There is an oral Irinotecan, which I like, at a dose of about 50/60mg/m2 Dx5. It is also in trial now for 'us' this way.

Besides w/Temodar, it is also used or in trial with:
*Oral etoposide aka: VePesidR
*Avastin - yes, honest for brain mets.


There is an older chemo 'Lomustine':
Lomustine Offers Effective Low Cost Treatment for Lung and Breast Cancer Brain Metastases (Doctor's Guide)
Reports results from a small study presented at the 14th International Congress on Anti-Cancer Treatment (ICACT) of the efficacy and toxicity of lomustine in patients with lung or breast cancer brain metastases. [2/03]
What this drug is used for:Treatment of brain tumors, both primary (developed in the brain) and metastatic

*And: Temodar w/Doxil -
2004 ASCO Annual Meeting
Category: Central Nervous System Tumors
Abstract No: 1576 Two CR and two PRs was recorded in the four patients with breast tumours,
Conclusions: the schedule was a well tolerated treatment (also in elder pts.) and has suggested an encouraging activity in brain metastases from breast.

*Topotecan:
Single-agent topotecan, especially in patients with SCLC or breast cancer, has demonstrated excellent response rates against brain metastases and may be safely and effectively combined with other chemotherapeutic drugs that have the ability to pass the intact blood-brain barrier....

*And these trials:
* ZK219477 in Patients With Breast Cancer and Brain Metastases
The purpose of this Phase II clinical trial is to determine the effects, both good and bad, of a new chemotherapeutic drug called ZK219477 that appears to cross the blood-brain barrier and penetrate into the brain.
* Epothilone B in Treating Patients With CNS Metastases From Breast Cancer
This phase II trial is studying how well a new experimental treatment known as epothilone B (patupilone) works in treating patients with CNS metastases from breast cancer that have recurred after whole brain radiation. Patupilone does cross the blood-brain barrier.

However, the trial Lani posted was terminated = Business decision. ?? the RTA 744

Gd, I pray you can find something for Ed to try. I'm focused on oral at the moment. IV's next... or whatever happens.

xoxopatty

[Lani]

Please see my post in the last couple of days of a new and more effective way of taking lapatinib00ie higher dose but intermittently

J Natl Cancer Inst. 2008 Aug 6;100(15):1092-103. Epub 2008 Jul 29. Links

Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain.

Gril B, Palmieri D, Bronder JL, Herring JM, Vega-Valle E, Feigenbaum L, Liewehr DJ, Steinberg SM, Merino MJ, Rubin SD, Steeg PS.
Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 1122, MSC 4254, Bethesda, MD 20892, USA.
BACKGROUND: The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. METHODS: EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 microm(2)) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22-26 mice per treatment group). All statistical tests were two-sided. RESULTS: In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%-53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell-derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell-derived brain metastases from vehicle-treated mice (P < .001). CONCLUSIONS: Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.
PMID: 18664652

[Lani]

here is one of her paper's abstracts:
Breast Dis. 2006-2007;26:139-47. Links

Brain metastases of breast cancer.

Palmieri D, Smith QR, Lockman PR, Bronder J, Gril B, Chambers AF, Weil RJ, Steeg PS.
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells.
PMID: 17473372

Thinking out louad. To get rid of the dormant cells, the bc stem cells, Dr. Max Wicha has started a trial of gamma secretase inhibitor (a drug normally tried vs. Alzheimer's so it must get into the brain)

How about seeing if those trials allow brain mets (U of Michigan, Baylor and one or two other sites if I recall correctly)

It is 224 am in Denmark, so got to get some ZZZZ

Try the website brainmets.org that Dr. Steeg advocates at all the meetings