I reviewed a couple of presentations on bronchioloalveolar carcinoma (BAC) at ASCO 2007, including one by Cadranal and colleagues in which patients with advanced BAC received single agent Iressa (abstract here).

Several members have raised questions in the last several weeks around the question of whether antacids like garden variety Rolaids or Tums, a class of drugs called histamine H2 blockers like zantac and tagamet, and also proton pump inhibitors (PPIs) like prilosec (the "magic purple pill"), protonix, nexium, etc. that effectively shut down stomach acid may actually be problematic if taken in combination with Iressa or Tarceva (I'm going to focus primarily on Tarceva here, since that's the drug marketed in the US right now).

A member recently asked me whether treatment in the second-line or later setting for advanced lung cancer would potentially improve survival at a cost of quality of life, or whether patients can benefit not only in terms of how long they live but also how they live during that time. Since advanced lung cancer, both NSCLC and SCLC, aren't generally able to be approached with curative intent, it's important for the treatment not to be worse than the disease. Ideally, patients will even feel better with treatment, rather than have to choose between quality of life (QoL) and quantity of life.

One of the themes that we've covered in some of the posts introducing the clinical entity of BAC is the variability in its natural history. In fact, much of what we've been learning about BAC has been in the last several years, and we're still learning more about it all the time. One of the things we've struggled with is the range of outcomes, that some patients can experience rapid deterioration and no response at all to EGFR inhibitors, while other patients can have a remarkably slow progression, and they sometimes will have an astounding regression of disease from EGFR inhibitors.

Throughout their development over the past years, the EGFR tyrosine kinase inhibitors Iressa (gefitinib) and Tarceva (erlotinib) have been identified as seeming to be particularly helpful in women compared with men. Only Tarceva is commercially available in the US, but Iressa is widely used in other parts of the world, including Asia, where it continues to be avidly used and studied. Both of these drugs have a consistently higher response rate in women, which has led to some different use patterns in women and men.

Inhibitors of the epidermal growth factor receptor (EGFR), such as Iressa (gefitinib) and Tarceva (erlotinib) are generally known for being often minimally toxic, oral, targeted therapies that can occasionally produce dramatic and long-lasting responses in a minority of patients and more modest, minor responses or prolonged disease stabilization in a larger proportion of patients. They are not widely considered as a treatment for brain metastases, but there are many reports that describe responses, including prolonged ones, of brain metastases to Iressa or Tarceva.

As I've described in a prior post, one of the most consistent findings in the work with the EGFR inhibitors Iressa (gefitinib) and Tarceva (erlotinib) is that never-smokers are far more likely to demonstrate a response and survival benefit than patients who do smoke or did smoke. Here, for instance, is the set of survival curves separated by smoking status for the large randomized trial of tarceva vs.

Before turning back to brain metastases, I wanted to cover a topic that has generated some recent questions, and that is the issue of potential interactions of tarceva with food and other drugs. Just as an introduction, the standard dose of single-agent tarceva in lung cancer is 150 mg by mouth daily, and this is meant to be taken on an empty stomach, at least one-hour before or two hours after eating.

We'll break from brain metastases for a while to talk about another potential avenue of targeted therapy in lung cancer: the cyclo-oxygenase, or COX, pathway.

Most of the focus on predicting response to EGFR inhibitors has been on identifing molecular markers that are associated with major response to this kind of treatment. But we know that there is a group of patients who get no benefit from these expensive drugs, and in these patients, EGFR inhibitors would just lead to side effects and keep them from a potentially more effective therapy for them.