When I first started OncTalk, there was a lot of buzz about celebrex (celecoxib) as a cancer drug, but almost all of it was among patients talking about it on the internet: oncologists watching the field hadn't been impressed by the early returns, including this one (despite the fact that some of my earliest work in lung cancer was on cyclo-oxygenase-2, or COX-2, the target of celebrex). I must admit that part of the idea of me providing commentary here was to provide a filter and a dose of healthy skepticism to keep people from being swept up by a tide of irrational exuberance about an unproven and largely untested drugs and approaches. Just over a year ago, I wrote a prior post about studies combining EGFR inhbitors like iressa (gefitinib) and tarceva (erlotinib) with celebrex or vioxx (rofecoxib); I wasn't very impressed, overall, although some early work by Dr. Karen Reckamp at City of Hope Cancer Center looked promising, with more work combining tarceva and celebrex ongoing.

But another article was published (abstract here) on the combination of celebrex (at a pretty high dose of 400 mg twice daily) and iressa (at a typical dose of 250 mg daily) as a first line therapy for advanced NSCLC, in an unselected population (not chosen by smoking status, EGFR mutations, COX-2 protein expression on the tumor, etc.). This study was conducted by the Hoosier Oncology Group (affectionately known as HOG) in Indiana, who enrolled 31 patients. They found that there was certainly activity, but the response rate of 16% and median survival of 7 months was on the low side for what you'd expect in a group of patients with advanced NSCLC who started with the standard approach of platinum-based doublet chemo (with or without avastin). Another concerning issue was that 2 of these 31 patients developed fatal interstitial pneumonitis, and inflammation of the lungs, a complication that can rarely occur with EGFR inhibitors, but I've never had a life-threatening or fatal case occur in the well over 200 patients I've treated with iressa or tarceva in the past 5-6 years, so having this occur in 2 of 31 patients, or 6%, is pretty concerning for the possibility that there is a danger to this combination.

It's possible that the results would have been better if they only enrolled patients who never smoked, or who had EGFR mutations or high expression of the COX-2 protein on their tumors. We can't say that this combination wouldn't be good for anyone, but this trial was a clear disappointment to the investigators and corroborates my belief that there is definitely no reason to deliberately combine these drugs in hopes of improving the impact as a lung cancer treatment outside of a clinical trial.