IRESSA CLINICAL TRIALS DISCONTINUED

[RandyW]

Iressa Clinical Trials Squashed Like A Nasty Cigarette Butt

The National Cancer Institute decided to discontinue Phase III clinical trials of Iressa (gefitinib). AstraZeneca designed Iressa to inhibit an enzyme, tyrosine kinase, that is critical to the growth of cancer cells. It was initially thought that the drug would prolong the lives of cancer patients who had completed chemotherapy.

AstraZeneca posted the following statement on their website iressa-us.com:

"AstraZeneca has recently received important new clinical trial data on IRESSA, from a trial which compared IRESSA to placebo in advanced non-small cell lung cancer patients whose cancer had progressed during chemotherapy or who could no longer tolerate chemotherapy. Our analysis of the survival data from the study shows that IRESSA did not significantly prolong survival in the overall population studied.

AstraZeneca is suspending promotion of IRESSA while the new study data are further analyzed and discussed with the FDA.

At this time, IRESSA remains commercially available, and physicians may prescribe IRESSA upon considering the various treatment options and deciding that it is the appropriate choice for individual patients. Patients now taking IRESSA should continue to take their medication and should consult their doctor."

If you are currently taking Iressa or its generic gefitinib, you should talk to your doctor about these new findings. Read more...

Iressa Drug Information

Lung Cancer

Chemotherapy

Tuesday April 19, 2005 | comments (0)

[gpawelski]

The cancer drug Iressa actually does work miracles, in "some" patients. The FDA limited Iressa's availability to cancer patients who have already taken the drug and whose physician believes it is helping them. Cell culture assays have found that a cellular signal for response to the drug can identify "some" responders but this limits Iressa's market profile significantly.

To the manufacturer, what good is the drug if it cannot be used by a broad base of the population? How will drug companies respond when studies show their drug to be highly effective, but only in 10% of the potential patient population? A failure? No, not by a long shot!

The Iressa situation is a great argument for pre-testing an individual's tumor. Iressa has been shown to benefit those that are benefitting from it. If the drug is working for some people, then obviously there are others out there who would also benefit. Who are those that benefit from its use? All the more reason to "test the tumor."

Assay-directed chemotherapy is an individualized approach to killing cancer. Cell culture assays are a bio-marker method used to determine what precise medications would kill the particular cancer. Doctors have assumed that stopping cell division would stop cancer, because most cancer cells divide and grow rapidly. But the approach didn't always kill the malignant cells. Cancer isn't a case of cells growing out of control, but of cells refusing to die on schedule.

There was a study using an angiogenesis assay, describing correlations between cell culture assay test results (cell death in response to Iressa exposure) and survival of 31 patients with non-small cell lung cancer who had received extensive prior chemotherapy. These correlations were based on the actual assay results which had been reported, in real time, prospectively to the doctors who had ordered the assay laboratory tests. There were striking correlations between test results and patient survival (not just response).

By inhibiting anti-apoptosis with Iressa, or even Tarceva (they are very similar drugs, small molecule inhibitors of tyrosine kinase, a key intermediary in the EGF cascade pathway), the cells undergo apoptosis and die. And it is detected at the whole cell level in the cell culture assays and reported out -- prospectively -- that this correlates strikingly with patient survival. It is a unique tool for identifying newer, better drugs, testing drug combinations, and serving as a "gold standard" to develop new DNA, RNA, and protein-based tests of drug activity.

EGF is Epidermal Growth Factor. EGF is a receptor on many normal tissues/cells, and also on many cancer cells. It is a growth hormone, locally secreted by cells. It attaches to a receptor on the cell membrane called EGFR (Epidermal Growth Factor Receptor). It then activates so-called signalling pathways within the cell, a cascade of biochemical events, including phosphorylation of proteins, leading to cell growth/proliferation/division. One type of an enzyme which is involved in the pathway which is involved in protein phosphorylation is called tyrosine kinase.

The EGF system is a target for a number of newer anti-cancer drugs, including Erbitux (a monoclonal antibody which binds to EGFR), and Iressa, Tarceva, the latter two being inhibitors of the EGFR-activated tyrosine kinase.

EGF-targeted drugs (Iressa, Tarceva, Erbitux) are poorly-predicted by measuring the ostensible target (EGFR), but can be well-predicted by measuring the effect of the drugs on the "function" of live cells. It is an area of cancer research which has been abandoned by the entire cancer research establishment. A bioengineering problem overcomed by a band of private-lab cell biologists.

More and more physicians and patients are turning to individualized therapies to treat cancers. Under this approach, scientists study how an individual's cancerous cells respond to several drugs. Doctors have learned that even when the disease is the same type, different patients' tumors respond differently to chemotherapeutic drugs. Without individualized testing, it's difficult to determine which drugs are best for patients who don't respond to standard therapies.

There are over numerous different therapeutic drug regimens out there. Any one or combination of them can help cancer patients. The system is overloaded with drugs and under loaded with wisdom and expertise for using them. What's needed is to make extensive use of bio-marker tests in treatment decisions.

Literature Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117

http://www.weisenthal.org/asco_06_egfr_ ... enthal.htm

The cell culture methodology maintains cancer cells in their native state, making cell-based assays of chemo compounds more reliable. The test relies on cells, rather than genetic tests, because the complexities and redundancies of human bioloty are beyond the ken of genomics.

The assay is the only assay that involves direct visualization of the cancer cells at endpoint. This allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record, which improves quality, serves as control, and assesses dose response in vitro (includes newly-emergent drug combinations).

http://weisenthal.org/ex_targeted_egfr_kinase.pdf

[aceking]

Hi. I'm writing on behalf of my friend Marc. He has NSCLC IIIB (now probably upstaged to IV due to tiny nodules in both lungs). He had GREAT results with a combo of Avastin & Gemzar and has had no treatment for over a year However, his scan last week showed slight progression of the nodules - his onc- Dr. Natale at Cedars Sinai in LA is doing a clinical trial that he would like to enroll Marc in in July. It is for high dose Iressa. I'm confused because I thought Iressa was pulled from clinical trials. Has anyone heard of this high dose clinical trial?? Your thoughts are greatly appreciated.

Debbi

[RandyW]

THIS SHOULD HELP YOU OUT AND THANKS FOR THE CONCERN

FDA ALERT [6/2005]:

FDA has approved new labeling for gefitinib (Iressa) that limits the indication to cancer patients who, in the opinion of their treating physician, are currently benefiting, or have previously benefited, from Iressa treatment. AstraZeneca plans to limit distribution of this drug under a risk management plan called the Iressa Access Program.

This information reflects FDA’s preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about, this information. FDA intends to update this sheet when additional information or analyses become available.

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To report any unexpected adverse or serious events associated with the use of Elidel, please contact the FDA MedWatch program at 1-800-FDA-1088 or http://www.fda.gov/medwatch/report/hcp.htm

Recommendations

Under the Iressa Access Program prescriptions for Iressa will be limited to the following patient populations:

patients currently receiving and benefiting from Iressa;

patients who have previously received and benefited from Iressa; and

previously enrolled patients or new patients in non-Investigational New Drug (IND) clinical trials approved by an IRB prior to June 17, 2005.

New patients may also be able to obtain Iressa if AstraZeneca decides to make it available under IND and the patients meet the criteria for enrollment under the IND.

Data Summary

Iressa, an orally administered epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, was approved for marketing in May 2003 for patients with non-small cell lung cancer (NSCLC) under Subpart H accelerated approval regulations that allow products to be approved on the basis of a surrogate endpoint for clinical efficacy. For Iressa the surrogate end-point was tumor response rate. The response rate in patients taking the drug was approximately 10%. The approved indication was for the treatment of patients who were refractory to established cancer treatments (both a platinum drug and docetaxel). However, since the initial approval of Iressa, Tarceva (erlotinib) has been approved for treatment of this same group. Tarceva was approved based on improved overall survival.

FDA has carefully reviewed data from two failed clinical studies of Iressa, one of which was required by the agency as part of the drug’s accelerated approval. This trial enrolled patients with regionally advanced or metastatic NSCLC who had failed one or two prior treatment regimens. In this large study, 1,692 patients were randomized to gefitinib or placebo. There was no significant survival benefit in the overall study population nor in patients who had high levels of a surface marker called “EGFR”. In contrast, the presence of EGFR at high levels appears to predict a good response to Tarceva.

In the second trial in patients with stage III NSCLC, after completion of induction and consolidation chemotherapy and radiation therapy, patients were randomized to Iressa or placebo maintenance therapy. No Iressa survival benefit could be demonstrated.

The Food and Drug Administration is not considering market withdrawal of Iressa at this time. New clinical trials are being developed, other ongoing trials are being completed, and there will be further analysis of the completed trials described above. These will determine the future role of Iressa treatment.

FDA Patient Information Sheet

http://www.fda.gov/cder/drug/infosheets ... nibPIS.pdf

Questions? Call Drug Information, 1-888-INFO-FDA (automated) or 301-827-4570

Druginfo@cder.fda.gov