Early data suggests that a combination of temsirolimus and bryostatin may be active in patients with rare forms of renal cell cancer, which are less likely to respond to other targeted therapies.
Elizabeth Plimack, M.D., M.S., a medical oncologist and attending physician at Fox Chase will report the trial results on Sunday, May 31 at the annual meeting of the American Society of Clinical Oncology.
"We have certainly seen sustained responses with this combination which are encouraging," Plimack says.
One of the patients with an extended response has papillary renal cell cancer, which is a rare form of the disease that does not respond well to standard therapies. "Patients with non-clear cell renal cell cancer, including papillary renal cancer, don't respond as well to tyrosine kinase inhibitors, such as sunitinib and sorafenib, as patients with clear cell renal cell. So there is an unmet need for therapy for these patients. We've seen that this combination may be active to some degree for them."
mTOR signaling promotes tumor cell proliferation and blood vessel development. Temsirolimus (Torisel), blocks signaling through one portion of the mTOR signaling complex, called TORC1, and slows tumor progression in patients with advanced kidney cancer. However, a second portion of the complex, called TORC2, is unaffected by temsirolimus and continues to promote cell proliferation. Therefore, Plimack and colleagues suspect that blocking TORC2 signaling activity could improve patient outcomes. Bryostatin blocks a downstream effector of TORC2, called protein kinase C.
Plimack and colleagues designed the phase I trial to test the safety of the bryostatin-temsirolimus combination. Twenty-five patients enrolled in the trial, including 20 patients with renal cell carcinoma. The phase I trial tested a combination of 20 micrograms/m2 bryostatin weekly plus one of the following temsirolimus doses, 10, 15, 25, or 37.5 mg, every 28 days.
The combination appears to be well tolerated in renal cell patients. Two patients developed dose limiting toxicities (one with renal toxicity and one with neutropenia) at the highest temsirolimus dose. Enrollment is now continuing with patients receiving 25 mg temsirolimus. (Two of the non-renal cell cancer patients developed dose-limiting toxicities early in the trial, after which point the investigators limited enrollment to patients who had not received prior chemotherapy.)
Early responses in renal cell cancer patients are promising, according to Plimack. Three patients have had durable partial responses to therapy. Two of those individuals are off therapy and have partial responses continuing at 3+ years and 12+ months, and a third patient continues on therapy with a partial response extending beyond 22 months.
Enrollment in the trial is on-going and complete data will be provided at the meeting.
Fox Chase Cancer Center is one of the leading cancer research and treatments centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, visit Fox Chase's web site at or call 1-888-FOX-CHASE or 1-888-369-2427.
Abstract #5111: A phase I study of temsirolimus (TEM) and bryostatin (BRYO) in patients with metastatic renal cell carcinoma (RCC). General Poster Session, Sunday, May 31, 2:00 p.m.-6:00 p.m.—Level 2, West Hall C
Diana Quattrone | EurekAlert!
Improving memory with magnets
28.03.2017 | McGill University
Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy