Daily Archives: August 6, 2009

PF-02341066 trial moving to Phase III

David, Peter and I drove to Boston early this morning for my routine trial appointment. The trial team has decided that I only need to come to the hospital once a month now.   My scan regimen has changed slightly as well. Although I must still have scans every two months, it won’t be necessary to get the abdominal scan each time. That means no more barium milkshakes for the moment. YES for small victories.   My oncologist, Dr. Shaw, just returned from the 13th WCLC (World Conference on Lung Cancer) in San Francisco this past weekend. At the meeting, Dr. Shaw presented updated data on the efficacy of the PF-02341066 trial. The results continue to be very promising and continue to generate excitement in the field of thoracic oncology.
The trial will soon enter Phase III. Prior to FDA approval of a drug, a controlled and randomized trial must be conducted.  It will be at multiple locations around the globe and will enroll many more people.  All those enrolling in Phase III must have the ALK mutation as well as only one failed first line therapy.  The fact that it is randomized means that some subjects will receive standardized chemo rather than the trial drug. However, should they suffer adverse effects from the standard chemo, or have progression of disease at their first scan at six weeks, they will be permitted to switch to the trial drug.  A phase II of the trial will be running simultaneously (the primary goal of Phase I is to assess for safety and dose escalation, Phase II is efficacy of the drug). Those subjects who possess the ALK mutation, but have also had more than one failed first line therapy, may enroll in a Phase II of the trial. So–bottom line–you need to have the mutation.

It was also fun to see images of my CT scans that were used as slides at the presentation. She also showed us a chart of subject response and it was interesting to see the hard data. Although my own response was characterized by my oncologist and the radiologist as “an almost total response”, statistically it is approx. a 70%  PR, or partial response.

It is beyond me how they determine such things (although Dr. Shaw explained that the methodology is to assess a two dimensional shrinkage of tumor as shown by scans). My CT scan could hardly look much better. However, I know that we are continuing to watch an area that represents either scarring or lung cancer. Only the statistical percentage is surprising, and I learned early in this journey to not pay too much attention to numbers. I just know how good I feel and that I continue to wake up every morning.  Wasn’t it Woody Allen who said that “80% of success is showing up”?
We also talked more about how the trial drug actually works.  The mutation that I have acquired (it is not inherited and so has been caused by exposure to one or more carcinogens) means that my DNA has been permanently altered, and altered in such a way that it makes cancerous cells.  The altered gene has become an oncogene:  a gene that contributes to the conversion of a normal cell into a cancerous one.  By locating where that mutation was (on the ALK gene), researchers were able to pinpoint a target.  The trial drug (PF-02341066) is a targeted therapy.   It is referred to as cancer growth blocker.  Growth factors trigger the cancer cells to divide and grow, and cancer cells are often very sensitive to them.  If these growth factors can be blocked, it is possible to stop growth and division of the cancer cells.

PF-02341066 is a Tyrosine kinase inhibitor.  This refers to the type of chemical that it blocks:  in this case, enzymes called tyrosine kinases.  These enzymes attach to a receptor on a cancerous cell and signal it to divide.  The Tyroisne kinase inhibitor stops that signal.  In layman’s terms:  my cancer has not been cured.  It has been stalled, the growth and division of cancerous cells halted, possibly indefinitely.

Realistically, it is unknown how long this drug will be effective for.  When and if it stops working, the cancer will begin to grow again.  I hope for two things: that the cancer will be held at bay for a long time, and that in the meantime, other treatments are developed.  This is the way it is with cancer.  We, all of us with cancer, are truly at the frontier.  There is so much yet to discover, and I am so grateful to those who are dedicating their life work to this end. My very existence depends on it.