A year after Iressa (gefitinib) was approved as a last resort for people with advanced non small-cell lung cancer, two studies published today may solve the mystery of why the pill is effective in only 10% to 15% of patients. Scientists in Boston and Japan have pinpointed mutations in a gene within the cells of some tumors—the gene that allows Iressa to work quickly against the cancer.

The discovery will help doctors identify which patients with advanced disease may have the best response to Iressa, and it could spark wider, perhaps earlier, use of the drug.

But it may not do so immediately, as a test to find the mutation is not yet available. Until one is developed, doctors trying to learn which patients may improve by using Iressa will have to give the drug for several weeks and watch closely for a response. Lung cancer patients interested in Iressa should talk with their oncologists or ask the doctors directing their treatment about a referral to one of these cancer specialists.

"[If] we know that a patient is likely to respond, we might be able to start treatment earlier with this drug that is more effective and has fewer side effects than standard chemotherapy," explained Thomas Lynch, MD, a lead author of the study published in the New England Journal of Medicine (NEMJ) (Vol 350, no. 21).

The FDA approved Iressa in May 2003 for patients with advanced non-small cell lung cancer (NSCLC) whose tumors continued to grow despite standard chemotherapy treatment. In earlier clinical trials, researchers noted that lung tumors shrank dramatically in a small percentage of patients taking Iressa.

It is not yet known if Iressa actually helps patients live longer. Possible side effects of the drug include diarrhea, nausea, vomiting, rash, acne, and a rare condition called interstitial lung disease, which can be fatal.

Lung cancer is the leading cause of cancer death for men and women in the US, expected to strike 173,770 people this year and cause 160,440 deaths. The findings reported today may have significant implications for the treatment of non-small cell lung cancer. This cancer type affects about 80% of people diagnosed with lung cancer, and is particularly difficult to treat.

In the NEJM study and another in the journal Science, researchers report finding the mutations in tumor samples from almost every patient who responded to Iressa, while no such mutations were found in those who did not respond. The patients who responded had certain characteristics in common, in addition to having non-small cell lung cancer. Most often, they:

• had never smoked or had
• quit smoking
• were female and/or were Japanese
• had bronchoalveaolar carcinoma or adenocarcinomas with brochoalveolar features

Researchers looked at genes that control a cell's epidermal growth factor receptors (EGFR). EGFRs are found on both normal and cancer cells. They help cells to reproduce, but in some of the lung tumors, these genes had mutated (changed) and triggered cancer cells to multiply very quickly. Surprisingly, the abnormal (mutated) genes also made lung cancer cells highly sensitive to Iressa, which blocks cell growth.

Patients who respond to Iressa generally see their symptoms improve within 10 days. Researchers reported that within a few weeks, Iressa caused some lung tumors to shrink by as much as 50%. Authors of the NEJM article found Iressa continued to hold cancer in check anywhere from a little over 5 months to more than 33 months.

Iressa belongs to a group of anticancer drugs called tyrosine kinase inhibitors. These medicines are "targeted therapies"—designed to attack cancer cells and leave normal cells largely untouched.

"This study has tremendous significance for the future of targeted therapies," said Eyre. "We are just beginning to understand targeted therapies, and this study opens the door to better understanding of potential combination therapies."

Call 1-800-ACS-2345 to talk with an ACS call specialist about cancer anytime day or night.

The American Cancer Society Clinical Trials Matching Service on this Web site may help find open trials of Iressa for lung and other cancers.

The National Cancer Institute has a clinical trials search at www.cancer.gov/clinical_trials.

AstraZeneca, the maker of Iressa, offers information about clinical trials, insurance coverage, and financial aid on their web site: www.iressa-us.com.

The Massachussetts General Hospital Cancer Center, where several key researchers work, plans more clinical trials of lung cancer treatments based on EGFR mutations and involving early stage tumors. Patients can call toll-free at 877-726-5130 or 800-388-4644 for more information.