The study I was just discussing, the French trial of Iressa at 250 mg daily for advanced BAC (abstract here), provided interesting clinical information, especially when viewed in the context of previous work on EGFR inhibitors in BAC.

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).

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.

Iressa was approved by the US FDA in May of 2003 as a third-line therapy, and for the next 18 months it was the only EGFR inhibitor on the market.

While lobectomy or pneumonectomy may be the surgical treatment of choice for most NSCLC tumors in younger, fit patients, a limited resection may be an ideal choice in certain settings. In my previous post I discussed the data supporting a limited resection in older patients, who are likely to have competing health risks that may make it less critical to pursue the most aggressive surgical strategy. Another situation in which a sub-lobar resection may be particularly appealing is when the tumor is quite small and/or has characteristics suggestive of an indolent natural history.

In my last post, I described the somewhat disappointing results for tarceva compared with chemotherapy in a trial of unselected advanced NSCLC patients with a marginal performance status. However, EGFR tyrosine kinase inhibitors like iressa and tarceva were developed as targeted therapies, so perhaps they might prove to be more effective if used selectively, in a targeted population.

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.

Just a few years ago, the only distinction in the field of lung cancer that meant anything was small cell vs. non-small cell. The different types of non-small cell, like adenocarcinoma vs. squamous cell vs. large cell, were of little interest and didn't change management (only a very recent development). And although we often asked about smoking history, the answer never changed our treatment plan.

As we established several years ago that it is indeed possible to do clinical trials with more than 50 or even 100 patients with advanced BAC, we were also seeing that those first forays into advanced BAC with standard chemotherapy were somewhat disappoingting (described further in another post).

Up until very recently, conclusions about the usefulness of chemotherapy among patients with advanced, diffuse BAC had generally been based on retrospective experiences with chemotherapy at a single center with a very limited number of patients. From such limited subsets, it is difficult to tell whether BAC is less responsive to standard chemotherapy than other forms of NSCLC, as is widely perceived, or if chemo is similarly helpful for BAC as for NSCLC in general.