Sorafenib, sunitinib provide no benefit to patients with locally advanced kidney cancer

Findings from a federally funded study suggest that patients with locally advanced kidney cancer should not be treated with either adjuvant (post-surgery) sorafenib or sunitinib. The average period to disease recurrence was similar between those who received sorafenib or sunitinib after surgery (5.6 years) and those treated with placebo (5.7 years). The study will be presented at the upcoming 2015 Genitourinary Cancers Symposium in Orlando.

"These drugs didn't reduce disease recurrence, but on average they did not appear to worsen patient outcomes either," said lead study author Naomi B. Haas, MD, an Associate Professor of Medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, Pa. "We are still analyzing the various groups of patients enrolled on this trial, and we hope that analysis of patient specimens collected on this study may provide clues into subsets of patients who might still benefit from these therapies."

Sorafenib, sunitinib provide no benefit to patients with locally advanced kidney cancer

Drug Duo of Ixabepilone and sunitinib Kills Chemotherapy-resistant Ovarian Cancer Cells......

In continuation of Sunitinib...

The use of two drugs never tried in combination before in ovarian cancer resulted in a 70 percent destruction of cancer cells already resistant to commonly used chemotherapy agents, say researchers at Mayo Clinic in Florida. Research  suggests that this combination (ixabepilone and sunitinib), might offer a much needed treatment option for women with advanced ovarian cancer. When caught at late stages, ovarian cancer is often fatal because it progressively stops responding to the chemotherapy drugs used to treat it. The finding also highlights the importance of the role of a molecule, RhoB, that the researchers say is activated by the drug duo. Neither drug is approved for use in ovarian cancer. Ixabepilone is a chemotherapy drug that, like other taxane drugs, targets the microtubules and stops dividing cells from forming a spindle. It has been approved for use in metastatic breast cancer. Sunitinib, approved for use in kidney cancer, belongs to a class of tyrosine kinase inhibitors that stops growth signals from reaching inside cancer cells.

                                           

     Sunitinib                                  Ixabepilone

Ref : http://www.mayoclinic.org/news2011-jax/6573.html

FDA panel votes in favour of Sunitib (Sutent) for pancreatic tumors....

In continuation of my update on sutent/sunitib....

 Pfizer Inc. announced this Tuesday that its oral multi-kinase inhibitor "Sutent" (see structure)  was determined as having a favourable benefit-risk profile by an oncology advisory committee of the FDA for the treatment of unresectable pancreatic neuroendocrine tumors. The panel voted 8-2 in favour of Sutent – generically called Sunitib malate.

Advanced pancreatic neuroendocrine tumour or NET, is a rare, life-threatening and difficult-to-treat form of cancer that accounts for approximately 22-28 percent of all neuroendocrine tumours. Nearly 90 percent of patients are initially diagnosed with locally advanced or metastatic disease, or cancer that has spread to other organs. An unresectable tumour is one that cannot be removed or resected by surgery.

 More...

Sutent or sunitinib malate targets vascular endothelial growth factor receptor or VEGFR and platelet-derived growth factor receptor or PDGFR, both of which are expressed by many types of solid tumours. The two targets are involved in tumours acquiring blood vessels, oxygen and nutrients needed for growth. 

Sunitinib was approved in 2006 in the United States for treating locally advanced or metastatic renal cell carcinoma and for imatinib-refractory or -intolerant gastrointestinal stromal tumour (GIST). It was approved for treating PNET in 2010 in Europe. A decision on approval is expected by the end of 2011, according to a company spokesperson....

Researchers able to predict and reverse resistance to Sunitinib treatment....

Van Andel Research Institute (VARI) researchers have found a way to  reverse resistance to Sunitinib (see structure), a treatment that is currently the first line of defense against clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Most patients who show a positive response to Sunitinib develop a resistance to the drug after one year of treatment.

Researchers lead by Dr. Teh, Bin Tean found that ccRCC tumor cells that had developed a resistance to Sunitinib had increased secretion of the protein interleukin-8 (IL-8). Administering Sunitinib and IL-8 neutralizing antibodies re-sensitized tumors to sunitinib treatment. Researchers also found that IL-8 may serve as a useful biomarker to predict patients' response to sunitinib treatment.

Interestingly,  another  study from same  group  of  Teh’s laboratory, looked into exactly how sunitinib works.  The study found that the treatment does not target tumor cells, but rather the tumor’s blood supply.

Researchers conclude that “it is now of critical importance to validate these findings in the clinical setting" and they hope that these insights will help to build upon recent advances to extend clinical benefits to more patients with metastatic kidney cancer....

Ref : 1.  Cancer Research 70, 1053, February 1, 2010. 

        2.  Cancer Research 70, 1063, February 1, 2010