Bench to Bedside: How to Fast Track Targeted Cancer Drugs with Radiation into the Clinic

Researchers from the translational research program of the National Cancer Institute and the Radiation Therapy Oncology Therapy Group have developed new guidelines to help fast track the clinical development of targeted cancer drugs in combination with radiation therapy.

The suggested strategic guidelines, published in the Journal of the National Cancer Institute in a recent commentary with lead author Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Thomas Jefferson University and Director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel, offers specific steps in the preclinical and early phase clinical trial process to get well-studied and novel targeted agents into the clinic more quickly.

Over the last decade, molecular agents that target cellular survival and growth, like Erlotinib and Sunitinib, have been developed but alone have had modest effect on improved survival. Combining such targeted agents with radiation therapy, however, has the potential to improve cure rates and long-term overall survival.

“There’s a missed opportunity in today’s cancer care treatment,” says Dr. Lawrence. “There is very promising laboratory data out there, but the clinical development of these new drugs with radiation has been limited. Here, we have put together a road map to help overcome obstacles and speed the development of new pipeline drugs with radiation.”

Adding radiation therapy to existing chemotherapy agents to radiation therapy has improved survival, and the authors of the commentary, which includes Adam P. Dicker, Chair of the Department of Radiation Oncology at Jefferson, believe new targeted therapies can follow in the same path.

“We know we want to repeat that success with new biological drugs,” says Dr. Lawrence. “In order to do that, we need direction, which is sorely lacking. These guidelines explicitly explain how much evidence is needed to go forward from the lab into the clinic, and furthermore how to design the clinical trials in humans.”

The guidelines discuss key questions when investigating specific targeted agents and tumor types, designing new clinical trials, such as the ‘time-to-event continual reassessment method design’ for phase I trials, and randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response.

It also discusses the role and purpose of preclinical studies in radiation oncology drug development and how to identify new, radiation response agents.

There are challenges to drug development with radiation, the authors explain. A major problem is the limited interest from the pharmaceutical industry in developing drugs with radiation, which is of special importance since the pharmaceutical industry fund a large amount of clinical cancer research. Furthermore, significant individual skills and institutional commitments are also required to ensure a successful program. The situation has been extenuated by the decrease in radiation biologists in recent years.

It is hoped that by providing a clear pathway, the guidelines will help the field overcome these barriers and create a focus and interest in drug development.
Some new approaches, the researchers say, include combining radiosensitizers with hypofractionated (high daily dose) radiation schedules and integrating immunomodulators with radiation therapy.

“We feel passionate that a a good way to push clinical care forward for cancer patients is by combining these two types of treatment: advanced radiation treatment together with the new generation of anticancer drugs,” says Dr. Lawrence. “We know where the future lies, and guidelines provide the path to bring us there.”

The full guidelines in the JNCI can be found here: http://jnci.oxfordjournals.org/content/early/2012/12/07/jnci.djs472.full



Dr. Bo Lu to Lead the Radiation Therapy Oncology Group’s Lung Cancer Translational Research Program

The Radiation Therapy Oncology Group (RTOG) announced that Bo Lu, M.D., Ph.D., of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, has been appointed chair of the group’s Translational Research Program (TRP) Committee’s Lung Cancer Subcommittee. The RTOG TRP Committee supports the integration of new scientific discoveries into the design of multi-center clinical trials.

Bo Lu, M.D., Ph.D., of Thomas Jefferson University Hospital and the Kimmel Cancer Center at Jefferson

Dr. Lu is professor in the Department of Radiation Oncology at Jefferson, where he also serves as director of the department’s Division of Molecular Radiation Biology.  Prior to joining Jefferson in early 2011, Dr. Lu was associate professor in the Departments of Radiation Oncology and Cancer Biology at Vanderbilt University School of Medicine and director of the Department of Radiation Oncology’s translational research program.  He is also a visiting professor of radiation oncology at Tianjin Medical University Cancer Hospital, in Tianjing, China.

“As a member of RTOG’s Translation Research Program Committee since 2009, it has been exciting to be part of research efforts incorporating novel cancer treatment strategies into the design of early phase, multicenter clinical trials,” says Dr. Lu. Among Dr. Lu’s basic science research interests are the development of drugs that cause tumor cells to be more sensitive to radiation therapy and that target lung cancer stem cells.

“Dr. Lu is internationally renowned for his work in translational radiation oncology, and I am enthusiastic about his leadership role with regard to guiding the RTOG’s translational research agenda in lung cancer,” says Adam Dicker, M.D., Ph.D, Professor and Chairman of Radiation O­ncology at Thomas Jefferson University and RTOG’s Translational Research Program Chair. “He has demonstrated talent for applying findings from the laboratory into clinical research,” remarks Dr. Dicker.

“Dr. Lu’s extensive basic science background and insight about promising new agents will be a tremendous asset to RTOG’s Lung Cancer Committee,” says committee chair and radiation oncologist Jeffrey Bradley, M.D., Associate Professor of Radiation Oncology at Washington School of Medicine. Dr. Bradley adds, “I anticipate an exciting and productive collaboration.”

“The opportunity to work with RTOG colleagues to advance new treatment options and improve clinical care for lung cancer patients is very rewarding,” says Dr. Lu, “and I am pleased to assume an expanded role within a research organization that promotes the robust evaluation of new therapeutic approaches in radiation oncology.”

Dr. Lu received his Ph.D. in cell and molecular biology from Baylor School of Medicine and his doctorate in medicine from Shanghai Medical University in China. He completed his residency in radiation oncology at the University of Southern California. Dr. succeeds Quynh Le, M.D., Ph.D. from Stanford University who recently was named chair of RTOG’s Head and Neck Cancer Committee.

“An important goal at the Kimmel Cancer Center is to foster translational medicine—taking basic science research and moving it closer to clinical practice,” said Richard Pestell, M.D., Ph.D., FACP, Director of the Kimmel Cancer Center at Jefferson. “With his lab investigations focusing on just that, and now this appointment to RTOG’s lung cancer subcommittee, Dr. Lu will no doubt help us discover safer and more effective treatments for patients suffering from this disease.”

For more information about RTOG and the group’s Translational Research Program: www.rtog.org

# # #

The Radiation Therapy Oncology Group (RTOG) is administered by the American College of Radiology (ACR), and located in the ACR Center for Clinical Research in Philadelphia, PA. RTOG is a multi-institutional international clinical cooperative group funded primarily by National Cancer Institute grants CA21661, CA32115 and CA37422. RTOG has 40 years of experience in conducting clinical trials and is comprised of over 300 major research institutions in the United States, Canada, and internationally. The group currently is currently accruing to 40 studies that involve radiation therapy alone or in conjunction with surgery and/or chemotherapeutic drugs or which investigate quality of life issues and their effects on the cancer patient.

The American College of Radiology (ACR) is a national professional organization serving more than 32,000 radiologists, radiation oncologists, interventional radiologists and medical physicists with programs focusing on the practice of radiology and the delivery of comprehensive health care services.