|
|
|
Lung Cancer and the Enzyme Connection
Erlotinib (Tarceva) was approved for treatment of progressive non-small cell lung cancer (NSCLC) after the BR21 study that showed that tarceva not only improved survival but also improved lung cancer symptoms and quality of life. This study and others have also taught us that the benefit of tarceva is much better in those who had never smoked and less effective in current smokers. It is important to note, however, that even those who currently smoke obtain a benefit from treatment with tarceva, albeit smaller.
In the wake of the BR.21 trial, it became known that certain EGFR mutations in the tumor are associated with a dramatic benefit with tarceva, as well as the other EGFR tyrosine kinase inhibitor (TKI) gefitinib (Iressa).We also began to realize that these EGFR mutations were found most commonly in never smokers and rarely in current smokers.
There it was: the reason why tarceva worked better in never smokers. But in fact that was not the whole story. Tarceva, like many other drugs, is broken down in the body by an enzyme group called CYP 1A1/1A2. Enzymes are proteins that help to break down and digest our food, but enzymes can break down and digest many other things as well. The products in inhaled tobacco smoke stimulate this enzyme CYP, which then further breaks down tarceva in the body before it has a chance to work.
Doc, Am I Too Old for Chemo?
The average age at which lung cancer is diagnosed in the US is 71. Would it be fair to say that at least half of those who are diagnosed with lung cancer are elderly? How do we define “old”? How does age impact the effect of chemotherapy?
Two decades ago, analysis of “older patients” who received chemotherapy for advanced lung cancer revealed that chemotherapy improved survival in the elderly to the same extent as in patients who were younger. The down side was that older patients experienced more side effects from chemotherapy. It is easy to see how this result could lead to mixed feelings: live longer, but with side effects. In the 1990’s clinical trials directed towards the elderly began. The pivotal trial was called ELVIS (Elderly Lung cancer Vinorelbine Italian Study). This study compared the effect of chemotherapy (vinorelbine) against no chemotherapy in lung cancer patients ≥70 years of age. This direct comparison clearly demonstrated that chemotherapy not only improved survival but most importantly, quality of life.
How was this possible? We all recognize that controlling the cancer will control cancer related symptoms. The challenge with treatment is balancing the side effects of chemotherapy against the benefit gained by controlling lung cancer symptoms. However, vinorelbine (Navelbine) is a well tolerated chemotherapy that made it possible to improve quality of life. Subsequently, more trials in more modern times with more modern chemotherapy have repeatedly shown us that chemotherapy is feasible and worthwhile in the elderly.
Learning from the Tumor: When Drugs Stop Working
Tarceva and Iressa (some of you may remember this drugs from a few years ago) have certainly become popular drugs for treating lung cancer, specially in the adenocarcinoma type of lung cancer. Drs. Pennell and West have discussed tarceva in other posts on this website – how it works, who benefits the most, what is the impact of certain mutations on the effect of the drug. Unfortunately, we are also too well familiar with the fact that these drugs don’t work forever and the cancer relapses even after having initially responded well. Fortunately, lung cancer scientists all over the world have been able to identify reasons why tumors become resistant to drugs like tarceva.
| Follow us on... |    |
||
Copyright ©2012 GRACE |
|||