Avastin & What Chemo?

[shonda]

Hello...

I am wondering if anyone has used any other chemo except Taxol with Avastin for treatment of metastatic breast cancer? I have been on Taxol over the past 4.5 years twice and we feel I have received all the benefit I will ever get from it. We have discussed some options, but I would like to hear from people that have actually experienced other chemos with Avastin.

Thank you
Shonda

[Jackie07]

Shonda,

I happened to come across this article - FDA's decision on Avastin is a personal one for breast cancer patients - today through the website of a brain tumor forum member:

http://www.tampabay.com/news/health/medicine/article1118371.ece

[Rich66]

It's been combined with Abraxane..a reformulation of Taxol which can work when Taxol has "failed".
I have also seen one patient on another site get to NED via Xeloda/Avastin.
The article Jackie posts is interesting to me since the success stories mentioned have continued their use..alone or when changing accompanying chemos. My sense..and some edumacated folks' contention, is that it might be the kind of drug that once begun, should be perpetually continued. (I imagine a lap band patient getting thin, then ballooning back up when the band is removed) Given the cost of the drug, I doubt that has typically been done in the studies being reviewed. Some argue there are other instances where uninformed administration protocols have hampered results and approvals. For example, non standardization of time of day might explain some of the difference between time regimented mouse and unregulated human studies. Dr. Hrushesky is a major proponent of chronotherapy (http://her2support.org/vbulletin/showthread.php?t=41606) and contends TNF was derailed because its toxicity was highly dependent on time of day administered.
There may be other less expensive and less toxic ways to get a similar antiangiogenic (http://her2support.org/vbulletin/showthread.php?p=221218#post221218) effect. Metronomic delivery (http://her2support.org/vbulletin/showthread.php?t=24729&highlight=antimitoti) of drugs and supplements seem to offer some of this. Nexavar/Sorafenib (http://her2support.org/vbulletin/showthread.php?t=41758&highlight=Sorafenib) might be an upcoming option as well.

[gdpawel]

Tykerb (lapatinib) enhances the antivascular activity of Avastin (bevacizumab) and has superior antivascular acitivity compared to Nexavar (sorafenib). The was a slide presentation at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium on September 5, 2008.

Antivascular activity of lapatinib and bevacizumab in primary microcluster cultures of breast cancer and other human neoplasms

Sub-category: New Systemic Agents - New drugs and targets (includes anti-angiogenics) - Other

Category: Treatment

Meeting: 2008 Breast Cancer Symposium

Session Type and Session Title: General Poster Session A

Abstract No: 166

Author(s): L. Weisenthal, D. J. Lee, N. Patel

Abstract:

Background: The following tyrosine kinase inhibitors (TKI) have been shown to have antivascular (AV) activity: sunitinib (Su), sorafenib (So), gefitinib (G), erlotinib (E), and imatinib (I). To date, AV activity has not been reported for lapatinib (LAP).

Methods: We studied the ability of TKI to induce tumor cell death (TCD) and also endothelial cell death (ECD) in primary human tumor cultures, using a novel functional profiling assay system, which detects TCD vs ECD in floating cell microclusters derived with > 90% success rate from fresh human tumor biopsies (Weisenthal, 2007 ASCO GI Symposium Abst 439; Weisenthal, et al. J Intern Med, In Press).

Results: LAP (15 µg/ml) induced significantly greater tumor cell death (TCD) in breast cancer biopsy specimens (n=25) than in specimens from cancers other than breast (n=42). However, there was no average difference between the degree of LAP-induced endothelial cell death (ECD) in breast cancer specimens vs. non-breast cancer specimens. At drug concentrations which were equitoxic to tumor cells, LAP induced significantly greater ECD than did sorafenib (So). At concentrations (2.5 and 1.25 mg/ml) of bevacizumab (BEV) which reduced VEGF in the culture media supernatant to levels below detection by commercial ELISA assay, BEV-induced ECD was not significantly enhanced by So, Su, G, E, or I; however, BEV-induced ECD was significantly enhanced by LAP.

Conclusions: 1. LAP has AV activity superior to that of sorafenib. 2. BEV + LAP may be the first clinically-exploitable AV drug combination. 3. Our functional profiling assay system may be used to individualize AV therapy. 4. High dose, intermittent 'bolus' schedules of LAP to coincide with BEV administration may be clinically advantageous, even in HER2-negative tumors.

Abstract Disclosures

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy and are designated with a caret symbol (^) here and in the print version.

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=58&abstractID=40418

Slide Presentation (large download 25.65 MB): http://weisenthal.org/Weisenthal_ASCO.pdf