In Phase I trials researchers test an experimental treatment in a few patients for the first time. The purpose is NOT to see if the treatment kills cancer cells, but only to:
- evaluate the drug's safety
- determine a safe dosage range
- identify side effects
What if the patients in a Phase I trial experience shrinkage of their tumors? Should this speed up FDA approval of the trial drug?
As explained in a NYTimes article, PLX4032 caused tumor shrinkage in nearly all the 32 patients with advanced melanoma who were treated in the Phase I trial. For most, the reprieve lasted less than a year. But life expectancy with advanced melanoma averages 8 months and quality of life can be miserable. Some patients nearing death improved enough to get out of bed and off oxygen for awhile (the so-called Lazarus effect)
Oncologists appealed to the FDA to provide accelerated approval for PLX4032 that would allow Roche to sell the drug, as long as it proceeds with the Phase II trial. For understandable reasons, Roche resisted:
- Doing so would handicap patient accrual for the $100 million Phase II trial. What patient is going to enter a trial with a 50% chance of getting standard therapy (with its notoriously high toxicity and low efficacy) if they can receive the promising new drug "off label"?
- Other companies are developing similar drugs. Roche needs the Phase II trial results to get FDA approval for a broader market than patients at the end-of-life.
Understandable. But is witholding accelerated approval ethical?