Bridging the Divide
Conquest - Summer 2008
By Sandi Stromberg
With two out of three adult cancer patients surviving their disease, researchers are finding they need to widen their focus beyond effective, life-saving treatments. Surviving with poor quality of life and heavy symptom burden is increasingly unacceptable in a world in which 22.4 million people have survived cancer.
Patrick Dougherty, Ph.D., is searching for a better understanding of the biologic mechanisms that cause peripheral nerve damage.
Fatigue, cognitive deficit, sleep disturbance and neuropathic pain are just some of the side effects with which survivors must deal. Yet, historically, there has been little research to understand the biologic mechanisms that cause them, the patients who are most susceptible to developing them or what kind of interventions might alleviate them.
“The problem is that many areas of importance to patients, especially side effects, have not been funded by the National Cancer Institute or the National Institutes of Health,” says Charles Cleeland, Ph.D., chair of the Department of Symptom Research at M. D. Anderson.
Paving way for new studies
This situation has brought about new opportunities for cancer research: a recent alliance between a pharmaceutical company, AstraZeneca, and a research-oriented cancer center, M. D. Anderson, in which “the design of these studies has been a true collaborative effort,” says Cleeland, who is co-principal investigator on this multifaceted study.
In the best of all worlds, these two entities would have joined hands long ago and worked in tandem to study and discover new treatments for cancer and the side effects of its treatments. However, collaborations between for-profit companies and non-profit institutions usually brought up the potential for conflict of interest.
So what has changed?
“Today, in the face of limited federal funding and squeezes on the NIH’s budget, research grants, especially in the area of reducing or preventing symptoms, are harder to obtain than ever before. Collaborating with AstraZeneca allows us to continue working toward helping our patients. But rest assured, M. D. Anderson and The University of Texas System have put extensive safeguards and conflict-of-interest policies and committees in place to help carefully cultivate relationships with the pharmaceutical industry,” Cleeland says.
“The development of strategic alliance relationships, such as this one between M. D. Anderson and AstraZeneca, also helps to combine the unique strengths of both partners to more effectively bring the newest drugs to patients faster,” says Robert Bast Jr., M.D., vice president of translational research at M. D. Anderson, who was instrumental in establishing the initial alliance to accelerate the evaluation and approval of anti-cancer drugs in 2006. “This research can now be extended to finding more effective supportive care for cancer patients and individuals dealing with the side effects of cancer.”
Bob Holland, vice president for neuroscience at AstraZeneca agrees. “We are excited to begin this collaboration with M. D. Anderson, which is at the forefront of discovering new ways of assessing and addressing pain symptoms associated with cancer treatment. We hope the insights we gain from this alliance will ultimately lead to new treatment options that will improve the quality of life for cancer patients.”
Filling a critical need
One of the foremost side effects to be studied under the terms of this agreement is chemotherapy-induced neuropathy, a common problem for patients receiving certain kinds of chemotherapy, such as paclitaxel, docetaxel, cisplatin, oxaliplatin, vincristine, thalidomide and bortezomib. If two or more of these agents are given in combination, the toxicity and potential for nerve damage increases.
“For up to 40% of patients who experience this distressing problem, it may limit the amount of chemotherapy he or she can receive, and become a chronic pain problem for some smaller percent of those patients,” says Allen Burton, M.D., professor and clinical medical director of M. D. Anderson’s Pain Management Center.
Together, he and Patrick Dougherty, Ph.D., professor in the Department of Anesthesiology and Pain Medicine, hope to identify neurobiologic differences between cancer patients who develop neuropathy and those who have little or no pain. This could give them a better understanding of the biologic mechanisms that cause this peripheral nerve damage, then help them design appropriate interventions.
“If we can limit toxic effects on the nervous system and thereby give full chemotherapy regimens, we may increase a patient’s survival, and hopefully also eliminate the long-term chronic symptoms that survivors deal with,” say Dougherty, co-principal investigator with Cleeland on these studies.
Reducing the symptom burden
“We are hopeful that the knowledge gained from this collaboration will enable us to design and validate new pain research models that can then be used to effectively test novel therapies in a preclinical setting,” says Andy Dray, chief scientist in the CNS and Pain Research Area at AstraZeneca.
While this research could lead to new treatments to prevent pain and thereby extend the therapeutic value of current chemotherapies, it also could help in the development of new chemotherapies with less severe, pain-related side effects.
Other parts of the project will study such treatment-related symptoms as cognitive deficit, fatigue and sleep disturbance, and explore potential common biologic mechanisms that may underlie these distressing symptoms.
“Our collaboration with AstraZeneca presents a unique opportunity to study ways of making cancer therapy much more tolerable,” Cleeland says. “Our overarching goal is to reduce the symptom burden of survivorship.”
In the fall issue, the series continues with the testing of new approaches to controlling multiple treatment-related symptoms.
Conquest - Summer 2008