Drug with Unique Disruption of Tumor Blood Flow Shows Promise

Newswise — Phase II study results of the agent ASA404 showed promise in patients with either squamous or non-squamous non-small cell lung cancer (NSCLC).

Results of this study, which were presented at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer, support ongoing Phase III studies of ASA404 in NSCLC.

Under development by Novartis, who licensed the drug from Antisoma, ASA404 (vadimezan) has a unique mechanism of action against a tumor’s blood supply. Scientists have long known that choking off this blood supply through a process called anti-angiogenesis is one way to slow tumor growth. Bevacizumab (sold as Avastin by Genentech) is one of many angiogenesis inhibitors and has had a major impact on patient care.

“Bevacizumab, however, predominantly interferes with the formation of new blood vessels,” said lead researcher Mark McKeage, Ph.D., an associate professor in clinical pharmacology at the University of Auckland. “ASA404 has been shown to cause selective disruption of the established tumor vasculature, inhibition of tumor blood flow and tumor necrosis.”

This unique mechanism of action could provide an option for patients with either squamous or non-squamous NSCLC. Treatment options for patients with advanced stage NSCLC are limited, particularly for those with squamous histology where some treatments exhibit limited efficacy or serious side effects.

“Standard chemotherapy is currently the mainstay of treatment for patients with squamous NSCLC. New targeted therapies and chemotherapies have been evaluated, but many show little promise as first-line treatments in patients with this type of cancer,” said McKeage.

McKeage and colleagues evaluated 108 patients with stage IIIb/IV NSCLC. Patients received six cycles of paclitaxel and carboplatin alone or the therapy cycles with ASA404. The researchers then compared the results by histology (squamous vs. non-squamous) and by treatment (chemotherapy plus ASA404 vs. chemotherapy alone).

Overall survival was much higher in patients treated with ASA404. In patients with squamous histology, survival was 10.2 months compared with 5.5 months among those treated with chemotherapy alone. In patients with non-squamous histology, survival was 14.9 months compared with 11 months among those treated with chemotherapy alone.

The addition of ASA404 did not appear to increase toxicity, and there were no serious adverse events associated with bleeding, pulmonary hemorrhage or hemoptysis. Rates of grade 3 or 4 anemia were not different, nor were rates of thrombocytopenia or neutropenia.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 30,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and nearly 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowship and career development awards. The AACR Annual Meeting attracts more than 16,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.