Early clinical trials suggested that shows that the addition of Afinitor to chemotherapy with Herceptin can overcome resistance to Herceptin. Preclinical data have shown that Afinitor, an inhibitor of mTOR, acts on the pathway that mediates Herceptin resistance and has the potential to help restore response in these patients. Afinitor works through direct antitumor activity and through its influence on two of the most important pathways for breast cancer, the erbB receptor and the HER2 pathways.
There are also trials, such as, Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer NCT01231659
This is a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.
Early clinical trials show that the addition of Afinitor to chemotherapy with Herceptin can overcome resistance to Herceptin. Preclinical data have shown that Afinitor, an inhibitor of mTOR, acts on the pathway that mediates Herceptin resistance and has the potential to help restore response in these patients. Afinitor works through direct antitumor activity and through its influence on two of the most important pathways for breast cancer, the erbB receptor and the HER2 pathways. The most recent presentation at the San Antonio meeting in 2011 suggested that the same is true of failure on hormones - that Afinitor can reverse nonresponsiveness to hormonal treatment.
There are also trials, such as, Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer NCT01231659. This is a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.
In 2011, a Phase III clinical trial (BOLERO-2) among 724 women was presented and generated a great deal of interest. All of the women had experienced cancer recurrence or progression in spite of treatment with Femara or Arimidex. Study participants were treated with Aromasin alone or in combination with Afinitor.
■Survival without cancer progression was 6.9 months among women treated with both Afinitor and Aromasin, compared with 2.8 months among women treated with Aromasin alone.
■The most common serious side effects in the Afinitor group were stomatitis (inflammation of the lining of the mouth; 7.7%), anemia (5.8%), shortness of breath (3.9%), hyperglycemia (4.3%), fatigue (3.7%) and pneumonitis (lung inflammation; 3.1%), and elevated liver enzymes (3.1%).
These results suggest that the addition of Afinitor to Aromasin improved outcomes among women with advanced breast cancer that had previously been treated with hormonal therapy. Afinitor has not yet been approved for use in breast cancer.
O'Regan, R., et al. RAD001 (everolimus) in Combinations with Weekly Paclitaxel and Trastuzumab in Patients with HER-2-Overexpressing Metastatic Breast Cancer with Prior Resistance to Trastuzumab: A Multicenter Phase I Clinical Trial. Poster presented at SABCS 2008.
Fasolo, A., et al. Multicenter Phase I Clinical Trial of Daily and Weekly Everolimus (RAD001) in Combination with Vinorelbine and Trastuzumab in Patients with HER-2-Overexpressing in Metastatic Breast Cancer with Prior Resistance to Trastuzumab. Poster presented at SABCS 2008.
Morrow P.K. et al, "Phase I/II trial of everolimus (RAD001) and trastuzumab in patients with trastuzumab-resistant, HER2-overexpressing breast cancer,"Abstract 1014, Journal of Clinical Oncology. Vol. 28, No. 15s, p. 117s.
I am a Chinese doctor, I was lucky to read this article and to be enlighten deeply. There're many many cancer patients in China because of environmental pollution. But in China, cancer research is still very backward as very little government investment in this area. I would like to further exchange with you.
Posted by: Fower Lee | June 28, 2011 at 11:40 AM