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Medscape Medical News from the:International Association for the Study of Lung Cancer.

Novel Tumor Vascular-Disrupting Agent Shows Promise in Lung Cancer

Roxanne Nelson

January 14, 2010 (Coronado, California) — The addition of the experimental agent ASA404 to standard chemotherapy appears to improve outcomes in nonsmall-cell lung cancer (NSCLC). The drug, also known as vadimezan and DMXAA, was originally developed by Antisoma, but has since been acquired by Novartis.

According to the pooled results of a randomized phase 2 trial and a subsequent extension study, combining ASA404 with conventional treatment increased survival in patients with advanced squamous and with nonsquamous NSCLC.

Among patients with squamous NSCLC who received the combination therapy, survival was 10.2 months; among those who received only chemotherapy, survival was 5.5 months. In patients with nonsquamous NSCLC, overall survival was 14.9 months for those who received combination therapy and 11 months for those who received chemotherapy alone.

We may have identified a better treatment option for patients with advanced lung cancer.

Adding ASA404 to standard therapy did not appear to increase toxicity, and there were no serious adverse events associated with bleeding, pulmonary hemorrhage, or hemoptysis.

Different From Other Vascular Disrupters

ASA404 is a small-molecule tumor vascular-disrupting agent that destroys existing tumor vasculature and selectively inhibits tumor blood flow, causing extensive necrosis of the tumor core.

Although treatment options for patients with advanced-stage NSCLC are limited, this is particularly true for patients with squamous histology, because some agents demonstrate limited efficacy or serious toxicity. With agents such as bevacizumab (Avastin) and sorafenib (Nexavar), different safety profiles have been observed in squamous and nonsquamous patients, he pointed out.

As an example, in a phase 2 study that combined bevaci-zumab with carboplatin and paclitaxel (J Clin Oncol. 2004;22:2184-2191), a higher proportion of patients with squamous NSCLC than with nonsquamous histology experienced life-threatening pulmonary hemorrhage after receiving bevacizumab (31% vs 4%).

The safety and activity study end points included response rate, time to tumor progression, and overall survival, and data from the histology subgroups and the treatment group were compared.

For all histologies combined, the median survival was 14.5 months for patients receiving the combination therapy and 8.8 months for chemotherapy alone. The most commonly reported grade 3/4 adverse events were blood and lymphatic disorders (n = 19; 18%).

"Lung cancer is the only cancer that kills over a million people a year," said Dr. McKeage. "Therapeutic advances have been gradual, incremental, and small in magnitude, but we are taking small steps forward."

The study was funded by Antisoma. Dr. McKeage reports consulting for and receiving research funding from Antisoma and Novartis.

American Association for Cancer Research-International Association for the Study of Lung Cancer (AACR-IASLC) Joint Conference on Molecular Origins of Lung Cancer: Prospects for Personalized Prevention and Therapy: Abstract A22. Presented January 14, 2010.

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