Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2-drug combination appears safe and active in metastatic kidney cancer

02.06.2009
Fox Chase Cancer Center investigators report that a two-drug blockade of mTOR signaling appears safe in metastatic kidney cancer in a phase I trial.

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!
Further information:
http://www.fccc.edu

More articles from Health and Medicine:

nachricht Routing gene therapy directly into the brain
07.12.2017 | Boston Children's Hospital

nachricht New Hope for Cancer Therapies: Targeted Monitoring may help Improve Tumor Treatment
01.12.2017 | Berliner Institut für Gesundheitsforschung / Berlin Institute of Health (BIH)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Midwife and signpost for photons

11.12.2017 | Physics and Astronomy

How do megacities impact coastal seas? Searching for evidence in Chinese marginal seas

11.12.2017 | Earth Sciences

PhoxTroT: Optical Interconnect Technologies Revolutionized Data Centers and HPC Systems

11.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>