Larry M. Weisenthal, M.D., Ph.D.
Two clinical trials showed that empiric combinations of bevacizumab (Avastin) and anti-EGFR antibodies, combined with chemotherapy, did not improve therapeutic outcomes in colorectal cancer – in fact, outcomes were inferior to single “targeted” therapy combined with chemotherapy.
Hecht JR, Mitchell E, Chidiac T, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 2009;27:672-680
Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009;360:563-572
In his video blog on Medscape, Dr. Maurie Markman editorializes that all new concepts must be proven in prospective, randomized clinical trials.
In the late 1980s, the NCI, aided and abetted by herd mentality study sections, effectively closed down research into fresh human tumor cell culture methods for testing and optimizing chemotherapy. The proof of this is the complete lack of NIH-funded studies relating to this topic appearing in PubMed for the last 15 years. Instead, we have put all of our clinical trials resources into trying to identify the best treatment for the average patient — in a disease notorious for heterogeneity. Drug screening (including therapy screening) belongs in the laboratory, not in the clinic. All of a sudden, there is a belated recognition that “personalized” therapy is worthy goal — yet 100% of the effort is going into static profiling of molecular markers, as opposed to dynamic, functional profiling of tumor response ex vivo. It’s crazy/nuts, and, down the road, tomorrow’s translational researchers will shake their heads and say “what on earth were they thinking?”
How to make progress in combined “targeted” therapy?
Here’s an example:
http://tinyurl.com/weisenthal-breast-lapatinib
But there’s absolutely no support for work such as this. And now there are efforts under way to make it impossible to do this work in grass roots, private sector laboratories, for example:
http://www.cancertest.org/?cat=11
One relevant irony is that, in my opinion, few individuals have done more to extinguish support for the development of cell culture methodologies in clinical cancer testing than the afore-mentioned Dr. Markman.
- Larry Weisenthal/Huntington Beach CA