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).

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.

I haven’t really covered the history or issues of directly comparing the two oral inhibitors of the epidermal growth factor receptor, or EGFR, which are Iressa (gefitinib) and Tarceva (erlotinib). This is really because over the last few years, gefitinib has had disappointing results in some important trials and is no longer readily used or available, while the remarkably similar drug Tarceva has been approved by the US FDA and is a standard treatment for patients with advanced NSCLC that has previously been treated with chemotherapy.

Although EGFR tyrosine kinase inhibitors and chemotherapy agents have been tested in previously treated patients with advanced NSCLC, and tarceva, alimta, and taxotere are all approved by the US FDA in this setting, we haven't had studies directly comparing chemo to targeted therapy. However, we're starting to get the first glimpses of information, including a randomized Phase III trial out of Japan that gave previously treated advanced NSCLC patients either iressa or taxotere.

The oral EGFR inhibitors Iressa and Tarceva both have activity in advanced NSCLC, with proven responses in a minority of patients and improvements in cancer-related symptoms as well.

Both standard chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) have been approved in NSCLC, and other anti-EGFR agents like erbitux/cetuximab and vectabix/panitumumab are also commercially available for treating other cancers and are being studied in lung cancer. Iressa was previously approved as a single agent in previously treated patients with advanced NSCLC, and Tarceva is now available but approved also as a single agent therapy. However, some oncologists give EGFR inhibitor therapies in combination with standard chemo.

After describing the association of a rash on EGFR inhibitors with overall better outcomes on this class of agents, we can now take a step back and recognize that the rash can be an annoyance at the very least and sometimes a real problem.

An acne-like rash or dry skin is a very common side effect of the drugs that target the epidermal growth factor receptor, with approximately 3/4 of patients who receive the EGFR tyrosine kinase inhbitor tarceva/erlotinib experiencing skin toxicity. Similar skin toxicities are also seen, but a bit less commonly, with the very similar drug iressa/gefitinib, and also frequently with erbitux/cetuximab, a monoclonal antibody that is less well studied in lung cancer.