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Xcytrin Clinical Trial Results Highlighted At ASCO
Results Demonstrate Unique Features and Importance of Brain Metastases in Lung Cancer -
Pharmacyclics announced today that the results of a Phase 3 trial with its investigational cancer agent, Xcytrin(R) (motexafin gadolinium) Injection, for the treatment of brain metastases, i.e. cancer that has spread to the brain from another part of the body, were highlighted during two "Clinical Problems in Oncology" sessions held this week at the American Society of Clinical Oncology (ASCO) Annual meeting in Chicago.
The sessions were chaired by Laurie E. Gaspar M.D., Professor and Chair of Radiation Oncology, University of Colorado Health Sciences Center, who described the results of the randomized Phase 3 clinical trial of Xcytrin. This trial established many of the unique features of brain metastases in lung cancer, including the observation that 46.6% of the lung cancer patients enrolled had brain metastases at the time of their initial diagnosis compared to 2.7% of the breast cancer patients. In addition, the study showed that 61.4% of lung cancer patients have brain metastases as their sole site of metastatic disease. Dr. Gaspar reviewed data from the trial showing selective localization of drug to brain tumors visualized using MRI and delay in time to neurologic and neurocognitive progression in lung cancer patients receiving Xcytrin.
Also in these sessions, Roy A. Patchell M.D., Associate Professor of Surgery, Division of Neurosurgery, University of Kentucky noted that in the Xcytrin trial, treatment was associated with a delay in time to neurological and neurocognitive progression in patients with lung cancer. He further reviewed how uncontrolled tumor growth in the brain is associated with serious neurological and neurocognitive consequences and reiterated that control of tumor growth, and therefore prevention of associated brain damage, are key goals of treatment since the majority of patients present with neurologic and neurocognitive deficits at the time of diagnosis of brain metastases.
"The data from our trial show that brain metastases in lung cancer occur very early in the course of the disease and are often the only site of metastasis," said Richard A. Miller M.D., Pharmacyclics´ President and CEO. "As indicated by the ASCO sessions, these data establish what are now recognized as important features of the clinical behavior of lung cancer and demonstrate the importance of brain metastases treatment in lung cancer management."
In addition to these presentations, other session speakers discussed the role of radiosurgery and surgery for patients with single brain metastases and the use of whole brain radiation therapy as a means to treat brain cancer.
"We are proud that the results from our randomized Phase 3 trial are helping to impact the clinical management of patients with lung cancer and brain metastases and furthermore that these findings help to elucidate the importance of this growing clinical problem in oncology," added Dr. Miller. "The results of this trial will be published shortly in a peer-reviewed journal and form the basis for our ongoing SMART trial, a pivotal Phase 3 trial in lung cancer patients with brain metastases using neurological progression as the primary endpoint."
The SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial, is designed to enroll 550 patients at over 100 leading medical centers in the United States, Canada, Europe and Australia. It will compare the effects of whole brain radiation therapy (WBRT) alone to WBRT plus Xcytrin in lung cancer patients undergoing treatment for brain metastases. The primary efficacy endpoint will be time to neurologic progression as determined by a blinded events-review committee. Survival and neurocognitive function will also be assessed as secondary endpoints of the trial.
About Xcytrin
Xcytrin is the first of an investigational class of drugs called texaphyrins, which are rationally designed small molecules that have a unique way of working inside diseased cells. Possessing a novel mechanism of action, Xcytrin is a tumor targeted generator of intracellular molecules known as reactive oxygen species (ROS).
After administration, Xcytrin selectively localizes and accumulates inside cancer cells, due to their high rates of intracellular metabolism, including anaerobic glycolysis. Because Xcytrin is a paramagnetic compound, its presence is visible with magnetic resonance imaging (MRI). Studies with MRI have confirmed the selective localization of Xcytrin in primary and metastatic tumors.
Within cancer cells, Xcytrin disrupts cellular metabolism, interferes with the flow of energy, and results in the generation of ROS. This mechanism of action of Xcytrin is believed to make cancer cells more vulnerable to the oxidative stress (i.e., specific types of damage involving oxidation-reduction reactions) caused by radiation therapy and chemotherapy. The generation of ROS within cancer cells promotes a process called programmed cell death, or apoptosis, leading to the selective destruction of the cancer cells.
Preclinical studies have shown that Xcytrin enhances the efficacy of radiation therapy and that of several commonly-used chemotherapy agents. Currently, Xcytrin is being investigated as a potential therapeutic in combination with radiation therapy and/or chemotherapy for various types of cancers in several clinical trials sponsored by Pharmacyclics and/or the National Cancer Institute.
In a recent large randomized clinical trial of Xcytrin and WBRT in the treatment of brain metastases, Xcytrin prolonged the time to neurological progression in non-small cell lung cancer patients with brain metastases who were receiving WBRT. In clinical studies, Xcytrin has been administered to more than 400 patients and was well tolerated.