Nexavar® May Overcome Resistance to Arimidex

[Rich66]

CancerConsultants.com
http://professional.cancerconsultant....aspx?id=42707

Nexavar® May Overcome Resistance to Arimidex® in Breast CancerResearchers from Georgetown University have reported that the addition of Nexavar® (sorafenib) to Arimidex® (anastrozole) helps restore sensitivity to Arimidex among women with breast cancer. These results were recently presented at the 2008 annual American Society of Clinical Oncology (ASCO) breast cancer symposium.
Arimidex is a hormone therapy that prevents the formation of estrogen in the body. It is commonly used among postmenopausal women with hormone-positive breast cancer. Unfortunately, some women can become resistant to Arimidex and others may never respond to Arimidex. Reasons for this lack of response are not clear. Researchers continue to evaluate ways to work around this resistance, such as targeting other biologic pathways associated with cancer.
Nexavar is an orally active, multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma and inoperable hepatocellular carcinoma. Nexavar is also being evaluated in patients with other cancers, including non–small cell lung cancer and melanoma. Used alone, Nexavar has not demonstrated activity for the treatment of breast cancer; however, researchers have speculated that Nexavar may aid in reversing the resistance to Arimidex or other hormone agents.
Researchers from Georgetown University recently conducted a clinical trial to explore the potential effectiveness of the combination of Nexavar and Arimidex in the treatment of advanced breast cancer that has stopped responding to Arimidex. This trial included 27 postmenopausal women with hormone-positive breast cancer who had no more than two prior chemotherapy regimens for their disease and who had stopped responding to prior therapy with Arimidex.

• Over 26% of patients achieved a partial response or stabilization of their cancer for at least six months.
• A reduction in endothelial cells in the circulating blood during the first week of treatment predicted a response to therapy.

The researchers concluded that the addition of Nexavar to Arimidex may help overcome resistance to Arimidex in postmenopausal women with hormone-positive advanced breast cancer.
Comments: Ultimately, these results support the idea that targeted therapies may be able to restore sensitivity to certain effective therapies in several types of cancers. Future trials further evaluating this approach are warranted.

[Rich66]

different use of same drug:

Sorafenib improves markers associated with survival in liver cancer

NOVEMBER 3, 2008
SAN FRANCISCO (Reuters Health) - The multiple kinase inhibitor sorafenib (Nexavar; Bayer) lowers levels of hepatocyte growth factor (HGF) and increases levels of vascular endothelial growth factor (VEGF), two markers that are associated with poor survival in hepatocellular carcinoma (HCC).
Findings of the phase 3 SHARP (Sorafenib HCC Assessment Randomized Protocol) study were presented here at the Presidential Plenary of The Liver Meeting 2008, the annual meeting of the American Association for the Study of Liver Diseases, by principal investigator Dr. Josep Llovet of the Hospital Clinic Barcelona, Spain, and Mt. Sinai School of Medicine in New York, NY.
In SHARP, 602 patients with advanced HCC were randomized to oral sorafenib 400 mg twice a day or placebo. ELISA was performed on plasma samples collected at baseline and after 12 weeks of treatment, assessing six plasma biomarkers (VEGF, soluble VEGF Receptor-2, soluble VEGFR-3, soluble c-Kit, HGF, and Ras p21) and one tumor biomarker (pERK).
Sorafenib significantly decreased the levels of c-Kit by 33.9%, HGF by 7.4%, sVEGFR-2 by 25.7% and sVEGFR-3 by 14.1%.
Sorafenib nearly doubled levels of VEGF, with an increase of 195.7% at 12 weeks.
"VEGF and c-Kit were independently associated with overall survival," Dr. Llovet told meeting attendees. "Low HGF levels and high c-Kit levels were associated with longer survival in patients treated with sorafenib."
Specifically, VEGF had a hazard ratio (HR) of 1.52 and c-Kit had a HR=0.76 for HCC survival. VEGF was also independently associated with survival (HR=1.98) and time to disease progression (HR=2.65) in the placebo cohort.
Low HGF levels were associated with improved survival (HR=1.681), as were high c-Kit levels (HR=0.56) in patients receiving sorafenib.
"This is the first drug to show positive findings in hepatocellular carcinoma," AASLD President Arthur J McCullough, MD, of Case Western Reserve University in Cleveland, Ohio, said in introductory remarks before Dr. Llovet's presentation.