March 26, 2010 Leave a comment
There is a common misconception that chemosensitivity-resistance assays are only useful for patients in the relapsed state once they have failed conventional first line therapy. This assertion is wrong on several levels.
- First, the best outcomes in cancer medicine are known to occur with first line therapies. The selection of the most active, least toxic drug or combination should be the goal of every physician at the time of initial therapy. As CSRAs have well established performance characteristics (sensitivity and specificity), their positive predictive accuracy (the likelihood that a patient with a sensitive assay will respond to the clinical treatments selected) are highest when they are applied in the first line setting.
- Secondly, on theoretical grounds, exposure to randomly selected chemotherapeutics, many of which are mutagens, may select for or induce drug resistance, diminishing the likelihood of a good outcome in second line or subsequent therapy.
- Finally, the introduction of active targeted agents provides patients the opportunity to receive first line therapies that do not carry the side effects and toxicities of classic cytotoxic chemotherapies. Our experience with first line Erlotinib in non-small cell lung cancer today provides response rates that exceed those associated with patients selected based on EGFr mutation or overexpression. Furthermore, the selection of candidates for combined targeted agents, e.g. EGFR & VEGF inhibitors, etc. provides a growing opportunity to introduce novel combinations into the first line setting. The growing cost and potential toxicity of some of these agents make the application of accurate selective methodologies increasingly crucial.
First line chemotherapy provides patients their best opportunity for a good outcome. There is no rationale for exposing patients to randomly selected toxic and potentially ineffective therapy when clinically validated selective methodologies can be applied in the first line as well as second line setting and beyond.