As described in one of my first posts, Avastin was approved by the US FDA for the first line treatment of advanced NSCLC in patients with non-squamous cancers, no history of coughing up blood, and no brain metastases, based on the positive trial ECOG 4599 (abstract here) that demonstrated a survival benefit for carbo/taxol/a

The AVAiL trial in first-line advanced NSCLC, based in Europe, was designed to confirm the role of avastin with chemo using a different regimen of cisplatin and gemcitabine with a placebo or Avastin at 7.5 or 15 mg/mg every three weeks (the European trial was placebo-controlled, unlike the US-based Avastin trial with carbo/taxol). I described it in a prior post that described a glimpse of the results that were reported in a press release a few months ago, but we received more information at ASCO.

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.

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.

A novel agent called motexafin gadolinium (MGd), with a marketed name of Xcytrin, has been studied as a potential neuroprotectant as well as radiosensitizer that may allow patients with brain metastases to do better when it as added to whole brain radiation therapy (WBRT) than they would with WBRT alone.

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.