As I've described in a prior post, there is some evidence that patients who develop a rash on tarceva (erlotinib) have an improved survival compared to patients who experience no skin toxicity on tarceva. The key question is whether this is an issue of under-dosing some patients, or if it's just a correlate of overall immune function or constitution in a person, in which case increasing the dose won't improve the outcome. The best evidence we have to address this issue is a trial by the Eastern Cooperative Oncology Group, ECOG 3503 (abstract here), in which 137 patients (118 eligible) with previously untreated advanced NSCLC were treated with first line tarceva, starting at the typical dose of 150 mg daily. But the dose was then escalated by 25 mg every two weeks until patients developed either grade 2 rash (scattered bumps or spots or general skin redness with itching or other symptoms) or significant other side effects that precluded dosing up to a maximum of 250 mg per day. Only half of the patients (60 of 118) ended up pursuing the dose escalation, presumably because the other half already had enough of a rash or other side effects that increasing tarceva dose wasn't feasible. Only 15 (13%) were escalated up to 250 mg daily. The overall response rate was only 7% (8/112, with one complete response), and the overall survival wasn't any better than you'd expect. This trial was actually presented at ASCO last year, but it's one that we heard almost nothing about. It hasn't been published as a full manuscript (that's not unusual, as it can easily take many months or a year or more to get a full paper drafted and accepted in a journal), but I suspect that this information hasn't gotten out there into the world because the results were pretty disappointing. But they do make an important point. So to recap, this trial showed that with aggressive dose escalation of tarceva, the response rate was less than was seen in the larger trial with 150 mg and then dose reduction as needed (abstract here); survival was also no better than you'd expect. So this really suggests that there isn't any incremental benefit to escalating dose. Patients who don't benefit on tarceva don't appear to be underdosed. The standard dose of 150 mg per day seems to be adequate, and there doesn't seem to be an incentive to increasing side effects. This isn't especially surprising for me, since I see that some of the patients who do very well on tarceva also do it on a reduced ongoing dose of 100 mg or sometimes lower when they're experiencing toxicity. You don't need to experience pain to receive the gain.