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Cisplatin/Gemcitabine/Herceptin Encouraging in NSCLC

Cisplatin/Gemcitabine/Herceptin Encouraging in NSCLC

SAN FRANCISCO—Early results with a regimen of gemcitabine (Gemzar),
cisplatin (Platinol), and trastuzumab (Herceptin) in advanced non-small-cell
lung cancer (NSCLC) patients overex-pressing HER-2 are encouraging, according
to a presentation at the 37th Annual Meeting of the American Society of
Clinical Oncology (ASCO abstract 1307).

The current standard-of-care chemotherapeutic agents used in NSCLC are
relatively similar in their ability to improve survival, quality of life, and
symptom relief. "So if we can find a way to improve these by adding
Herceptin in a practical manner, then patients will benefit," principal
investigator Ralph G. Zinner, MD, assistant professor of medicine at M.D.
Anderson Cancer Center, told ONI in an interview.

Co-investigator is Roy Herbst, MD, PhD, assistant professor of medicine and
cancer biology.

The current phase II study addresses several issues, primarily efficacy vs
historical controls. Dr. Zinner said that chemotherapy response rates in three
phase III NSCLC trials of the cisplatin/gemcitabine combination have been
around 35% (40.6%, 31%, and 40%). "We felt that achieving a 55% response
rate by adding Herceptin would be good evidence of benefit," Dr. Zinner
stated.

He noted, however, that use of historical controls who did not receive
trastuzumab as part of their chemotherapy regimen is complicated by the absence
of response data in patients identified as having HER-2 overexpression. This is
important, he said, since HER-2 overexpression may predict either better or
worse response to standard chemotherapy.

Assessment of HER-2 overexpression was another area of study interest. Dr.
Zinner pointed out that fluorescence in situ hybridization (FISH) was not used
because in NSCLC (unlike in breast cancer), DNA amplification is not the usual
mechanism of overexpression. Through poorly understood mechanisms, within the
subset of lung cancer tumor tissues that overexpress HER-2, only a small
percentage have such DNA amplification detectable through FISH.

Immunohistochemistry (IHC), however, does detect the HER-2 protein gene
product in lung cancer. Dr. Zinner said that preclinical studies have shown
antibodies against HER-2 to have antipro-liferative effects even without DNA
amplification.

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