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Old 11-01-2009, 02:29 AM   #3
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,778
Re: preclinical: metronomic chemotherapy (oral) produced remarkable prolongn of survi

Yes, I just heard Dr. Kerbel speak on a similar protocol at the San Diego conference I attended mid-October.
Among what he discussed:
Clin Cancer Res. 2009 Oct 15;15(20):6358-66. Epub 2009 Oct 13.
Comparative impact of trastuzumab and cyclophosphamide on HER-2-positive human breast cancer xenografts.
Francia G, Man S, Lee CJ, Lee CR, Xu P, Mossoba ME, Emmenegger U, Medin JA, Kerbel RS.

Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada. robert.kerbel@sri.utoronto.ca
Comment in:

Clin Cancer Res. 2009 Oct 15;15(20):6311-3.
PURPOSE: Metronomic chemotherapy is a minimally toxic and frequently effective new treatment strategy that is beginning to show promising phase II clinical trial results, particularly for metastatic breast cancer when combined with various molecularly targeted antitumor agents. Here, we assessed a treatment strategy that uses trastuzumab plus daily oral metronomic cyclophosphamide on metastatic Her-2-positive human breast cancer models. EXPERIMENTAL DESIGN: Treatments were initiated on orthotopic transplanted primary tumors as well as established visceral metastatic disease of two independent Her-2-positive breast cancer models, both independently derived from the human MDA-MB-231 breast cancer cell line. Outcome was assessed by noninvasive measurements of tumor cell-secreted human choriogonadotropin in the urine as a surrogate marker of relative tumor burden, or by whole body bioluminescent imaging, in addition to prolongation of survival. RESULTS: Orthotopic primary tumors responded to trastuzumab monotherapy with significant growth delays, whereas minimal antitumor effect was observed when mice with metastatic disease were treated. Nevertheless, trastuzumab showed a benefit in this latter setting when combined with metronomic low-dose cyclophosphamide as assessed by prolongation of survival. This benefit was similar to trastuzumab plus maximum tolerated dose cyclophosphamide, but was associated with lesser toxicity. CONCLUSIONS: Trastuzumab combined with metronomic cyclophosphamide may be an effective long-term maintenance strategy for the treatment of Her-2-positive metastatic breast cancer.

PMID: 19825954
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