Which chemo drug DOES cross the B.B.B?

[jojo]

BBB stands for "brain blood barrier".

I had been on Xeloda, since Sept 2005. Once I was discovered with a brain met, they stopped my Xeloda immediately. I am still on weekly Herceptin, though.

I am aware that Herceptin does not cross the BBB, but what about the rest of chemo drugs? My nurse practitioner just said that most chemotherapy drugs don't cross the BBB.

Thanks for any imput.

[Joe]

Jojo,

Thermador is one drug that crosses the BBB. I believe PattyZ is currently being treated with it.

Also GSK is conducting widespread clinical trials of Tykerb (Lapatinib) with some success. See the article from the Boston Globe published yesterday.

Regards
Joe

[mamacze]

Joe (and JO Jo),

Thank you for the question and your update. Lapatinib is getting alot of attention on the east coast here through the Boston Globe article. But I wonder about some of the other clinical trials noted on the NIH web site; ie, "combined monoclonal antibodies trastuzumab and pertuzumab", and "WBR with supplemental Oxygen, with or without concurrent RSR13", are either of you aware of these other trials and have you heard which ones seem to be the most promising?
Love Kim from CT

[Joe]

pertuzimab is also known as Omnitarg , I havn't seen any results yet.

RSR13 is manufactured by Allos Pharmaceuticals and has shown to make WBR more effective.

Regards
Joe

[al from Canada]

JoJo and Kim,

Apart from the drug, (Tremodar) that Joe mentioned, only "small molecule" inhibitors cross the BBB. The two that are approved (for other cancers) that do cross the BBB are Iressa and Tarceva and then lapatinib; which isn't approved for anything yet. There are others that target multiple pathways that I am less familiar with such as Nexavar® (sorafenib) and Sutent® (sunitinib), and pertuzumab, and Avastin which targets VEGF. I don't know if any of those cross the BBB and in terms of Avastin, I don't think the researchers know either. Pertuzumab is a monoclonal antibody therefore it is a large molecule drug and willmot cross the BBB.
Linda just completed the RSR3 trial with WBR and I guess time will tell how well it works.

I hope this has helped,
Al

jojo,
Technically speaking, the molecular weight of Xeloda and Gemzar is small enough to pass the bbb. Temodar for sure. I have had success since Sept. with the combo of Temodar/Xeloda.

A small study done using these two agents showed some positive results as well.

Gemzar has also been combined in a study with Temodar for brain mets.

GEMZAR : molecular wgt.= 299.66
TEMODR : molecular wgt.= 194.15
XELODA : molecular wgt.= 359.35

This one below was specific to bc brain mets:

SABCS ABSTRACT:
[San Antonio Breast Cancer Symposium]
[1079] Phase I study of capecitabine (C) in combination with temozolomide (T) in the treatment of patients with brain metastases from breast carcinoma.

Rivera E, Valero V, Francis D, Brewster A, Royce M, Esteva F, Murray JL, Pusztai L, Hortobagyi GN.. The University of Texas M.D. Anderson Cancer Center, Houston, TX


Background: T is an oral alkylating agent that is
currently being used for the treatment of primary
brain tumors due to its ability to cross the
blood-brain barrier. C has been approved for use in
the treatment of metastatic breast cancer patients who
have failed anthracyclines and taxanes. It is well
known that C crosses the blood-brain barrier and has
activity in the brain. Options are limited for
patients with brain metastases.

Materials and Methods: We evaluated the activity of
both drugs in combination for the treatment of brain
metastases not amenable to surgery. Patients were
allowed in the study if they had new onset brain
metastases from breast cancer, had declined radiation
therapy, and were neurologically stable. They were
also eligible if they had evidence of recurrence or
progression of brain metastases after whole brain or
stereotactic radiation therapy. C was started at 1800
mg/m2 in 2 divided doses. T was given at a starting
dose of 75 mg/m2 in one daily dose. Each drug was
given concomitantly every day for 5 days (day 1-5)
followed by 2 days of rest and restarted again for an
additional 5 days (days 8-12). Each cycle was repeated
every 21 days. We have enrolled a total of 16 pts — 6
pts at dose level 0 (C/T — 1800/75), 6 pts at dose
level 1 (C/T — 1800/100), and 4 pts at dose level 2
(C/T — 2000/100).

Results: Five pts had recurrent brain metastases and
had been previously treated with radiation therapy.
The median age is 51 yrs (range, 32-77). All pts had a
Zubrod performance status < 1. Ten pts were ER and/or
PR positive. No grade 4 toxicities have been reported.
Grade 3 toxicity includes headaches (2 pts), vomiting
(1 pt), constipation (2 pts), fatigue (2 pts),
nonneutropenic fever (1 pt). We have observed 1 CR, 1
PR, 6 MR, and 3 SD. Four pts did not respond to
treatment. One pt was not evaluable for response.
Median duration of response in brain was 10.5 weeks
(range, 6-48+ wks). Two pts with SD and 2 pts with MR
had previously received whole brain radiation therapy.
Three pts were taken off the study because of
progression of disease outside the brain including the
pt who had a CR in brain but progressed systemically.
Four pts are actively being treated in the study.
(me would equal: 2808-3120 Xeloda & 117-156 Temodar / currently on 2000 Xeloda & 250 Temodar)

Conclusions: The combination of C and T seems to be
active and well tolerated for the treatment of brain
metastases from breast carcinoma. Further studies
should include the evaluation of this combination with
radiation and as adjuvant therapy in those pts who are
at high risk of developing brain metastases.

Wednesday, December 8, 2004 4:30 PM

Poster Session: Treatment: Chemotherapy -- New Drugs and Formulations (4:30 PM-7:00 PM)


(This one lung brain mets):

Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer.

Ebert BL, Niemierko E, Shaffer K, Salgia R.

Departments of Adult Oncology and Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts, USA.

The use of chemotherapy for the treatment of brain metastases arising from lung cancer has been limited by poor efficacy and high toxicity. Temozolomide, an orally bioavailable alkylating agent that crosses the blood-brain barrier, has activity against brain metastases from both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) when used as a single agent, but response rates are low. Preclinical experiments and early clinical studies in other malignancies indicate that temozolomide may have additive or synergistic effects when used with other chemotherapeutic agents. We report a case of a patient with SCLC with recurrent brain metastases after treatment with multiple chemotherapeutic regimens and whole-brain radiation therapy (WBRT) who was treated with temozolomide (150 mg/m(2) for 5 days in a 28-day cycle) and oral etoposide (50 mg/m(2) for 10 days in a 28-day cycle). A second patient with NSCLC and brain metastases who progressed after treatment with chemotherapy and WBRT was treated with temozolomide (150 mg/m(2) for 5 days in a 28-day cycle) and gemcitabine (1,000 mg/m(2) weekly for 2 weeks in a 3- week cycle). In both patients, the temozolomide regimens were extremely well tolerated and resulted in dramatic and durable responses. The combination of temozolomide with other chemotherapeutic agents represents a promising strategy for treating patients with lung cancer and recurrent brain metastases and merits further study.

Publication Types:
Case Reports

PMID: 12604733 [PubMed - indexed for MEDLINE]

xoxoxhugs,
patty

[eric]

I continue to be amazed by the quality of information that channels though this site! Great stuff.

[AlaskaAngel]

I think so too. However, there is so much to learn here that it can be overwhelming, especially to new users or those who are hoping to find a way here to get a handle on immediate concerns about their own situation. I'm not the brightest bulb here by any means, but there is room here for more than just discussion of highly technical information -- which is why I think some people are frustrated and are pointing out that the proper place for articles may not be on the main board. For those who are trying to pop in once a day to see if their concerns have had any responses, subjects do end up "out of sight" pretty fast and if people are looking for more than just one or two responses, once they are out of sight they don't get much attention. I don't understand all that I read here in the technical material, but I am very, very grateful for just being exposed to it as a challenge and hope it continues.

The frustration some feel is evidence of how important and useful this board has become.

AlaskaAngel

[al from Canada]

Here is a list of brain cancer trials, primary and mets. If you read through them, I would assume most of the drugs in the trials do cross the BBB.
Al

http://www.virtualtrials.com/new.cfm

[mamacze]

Al and JoJo and Pattyz,
Thank you all for your comments and suggestions. I am having frequent brain scans now because of constant headaches so I feel like I need to "bone up" on all this info now. I want to be prepared if they discover mets. Al, I am so glad to hear Linda has finished her RSR3 trial...I have been thinking of you both; I so hope that she can continue to show us the way.
Love Kim

Al,
Nah, don't assume that at all... more like throwing enough mud and hoping something will stick. There are so many unknowns, so many variables, so many kinds of brain tumors/cancer with mostly pretty negative end results... Lots of medical head scratching to find real treatments with positive results.

My med onc tried Xeloda alone for a gal with brain mets because of a report I had given him. He told me later that she had responded well and that made me glad. For her and my onc. We really just never know until we try something.

Very best to you and Linda,
pattyz

[al from Canada]

Patty,

Thanks for the sound advice....sometimes we get carried away with wishful thinking.
Al

Patty- My sister's onc has been hesitant about temodar for bc mets to the brain, and I would like him to learn of your results from a medical source. Could you tell me where you are being treated and who your onc is? My email is mabhunter44@yahoo.com, if you don't want to post it on board. Thank you.

Unregistered:

about your sister's doc and info...

Just go back a page in this thread and copy the info from the San Antonio BCS on the small study using Xeloda and Temodar for bc patients w/ brain mets. Titled: [1079] Phase I study of capecitabine (C) in combination with temozolomide (T) in the treatment of patients with brain metastases from breast carcinoma.



I'm in Minnesota, USA. My onc is a 'generalist'. The treatment combo I am on was created by him, because of my own research. I have 'safely' used up total dosage of rads for my brain mets, so this is a 'last ditch' effort to control another recurrance.

I can't imagine why an onc would be hesitant to try Temodar if other treatment procedures had been done, or even in combination with rads, as that is what many of the current trials are doing.

Hope that helps in some small way.

pattyz

Hi Patty,

Thank you very much for the information. My sister is currently being treated with Stereotactic Radiation Therapy as the lesions appear, which has been 1 or 2 small occurrences a couple of times, and they have responded well so far to the SRS. She already had WBR and a craniotomy initially when brain mets were first detected. We are hoping and praying for a series of clear MRIs in the future. Herceptin has been keeping the rest of her body clear, and she is doing remarkably well otherwise. She was in the Lapatinib trial for a few months last year, but while it helped another bc patient we met, it didn't work for my sister. I'm trying to keep up on what might be advisable next, if things accelerate. I'm so glad the Temodar is working well for you - more power and blessings to you, and thank you so much for sharing your experience on this board. You've got a larger cheering group than you know praying for your health!

I have just been in our public library looking through books on all aspects of health where there is discussion of omega threes, sixes and fat intake.

A book onmental health depression highlights the importance of fats in brain health and particularly points to the benificial effects of omega three and balancing the threes and sixes in brain maintentance and repair.

I also recollect some trials looking at the suject on NCBI.

RB