[gdpawel]

Joan M

After reading Moss' book, you'll get a good understanding of your statement, "testing patients upfront is not the best interest of pharmaceutical companies." Pharmaceutical companies do not want them testing patients who aren't going to be responsive to their drug product. They like testing for their product, not someone else's product.

With some of these prognostic tests, it can eliminate some patients from having to receive chemotherapy treatment. With some of the functional profiling tests, it reveals those drugs that work from those drugs that don't (and this is what's important), on the "individual" cancer cells, not from average population studies.

The problem with genetic tests (a.k.a. Tarceva) is that it never even tests the individual's cancer cells against the drug (compatibility is not tested clinically). Molecular testing methods detect the presence or absence of selected gene or protein mutations which "theoretically" correlate with single agent drug activity. Cells are never exposed to anti-cancer agents. And it cannot test sensitivity to "combinations" of targeted drugs.

Even patients who are found to have an activating EGFR mutation, Tarceva is considered acceptable but not a definite superior choice. Genetic variations alone do not determine response to targeted therapy. Those patients who test negative for EGFR are left to the same guesswork as conventional therapy.

There are lots of things which determine if the drug works, beyond the existence of a given target. Does the drug even get into the cancer cell? Does it get pumped out of the cell? Does the cell have ways of escaping drug effects? Can cells repair damage caused by the drug?

Tarceva can be given selectively to patients with EGFR negative NSCLC. It is a challenge to identify which patients targeted treatments like Tarceva will be effective. Patients across a broad range of clinical characteristics could benefit. Being EGFR negative is no reason not to be given this drug.

BTW. Tarceva is not just for lung cancer. Tarceva is a tyrosine kinase inhibitor. However, it also has an anti-angiogenic effect on cancer cells. There are a number of classes of drugs that target angiogenesis (VEGF). At the protein level is Avastin. At the tyrosine kinase level is Iressa, Nexavar, Sutent and Tarveca. At the intracellular metabolic pathway mTOR level is Afinitor and Torisel.

When chemotherapy drugs work, they often cause tumors to shrink a lot, sometimes even making them disappear. But anti-angiogenesis drugs don't seem to work in the same way. In some cases they shrink tumors, but in others they just seem to stop them from growing any larger.

Newer approaches to treatment that combine anti-angiogenesis drugs with chemotherapy, other targeted drugs, or radiation may work better than using them alone. For instance, early studies that tested the drug Avastin by itself did not find that it helped people with cancer to live longer. But later studies found that when it was combined with chemotherapy to treat certain cancers, it helped people (some subsets of patients) live longer than if they got the chemotherapy alone.

Doctors aren't sure why this is the case. One theory is based on the fact that chemotherapy drugs may have a hard time getting to cells in the middle of tumors. Tumor blood vessels grow in a short amount of time and in an abnormal environment, so they are not as well-made and stable as normal blood vessels.

Because of this, they tend to be leaky. This affects how well drugs can reach the inside of the tumor. The theory is that anti-angiogenesis drugs may somehow stabilize these tumor blood vessels for a short period of time, allowing the chemotherapy to reach more tumor cells and be more effective.

Greg