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.

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.

While we are still working on figuring out the mechanisms underlying differences in the lung cancers of women vs. men, the efficacy and survival paint a consistent picture that women with lung cancer live longer than men regardless of the lung cancer subtype, stage, or treatment used (summary here). Large studies have reported that women have an approximately 15-20% improvement in survival, controlling for other variables, when compared to 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.

Over the last several years, chemotherapy after surgery has become the standard strategy for improving survival compared to surgery alone, at least for stage II and IIIA patients who don't have mediastinal (N2) lymph nodes involved, and it's often used also for patients with stage IB NSCLC (no lymph nodes, but a larger tumor or tumor involvement with the pleural lining around the lung). However, another approach that has been studied, albeit less so than adjuvant (post-operative) chemotherapy is neoadjuvant (pre-operative, also known as induction) chemotherapy.

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.