Although we are all frustrated by the relatively slow pace of progress in lung cancer, there are times when we can look back and feel that we have made a real impact. Six years ago there were no treatments that were FDA approved and appeared to benefit patients who had previously been treated with first-line chemo for NSCLC. Now there are several.

Stage IIIA NSCLC, particularly with N2 lymph node involvement, is probably the NSCLC treatment setting that is most controversial. While it is the latest stage that we routinely consider surgery for, it is actively debated whether patients with stage IIIA NSCLC should have surgery or be treated with a combination of chemo and radiation without surgery.

Locally advanced, or stage III, NSCLC, can potentially include patients for whom surgery is an option, but for many patients with stage IIIA and a majority of those with stage IIIB NSCLC, a non-surgical approach is the best treatment recommendation. It's important to keep in mind that the goal of treatment for patients with locally advanced NSCLC but who don't have a malignant pleural effusion (fluid inside the chest but outside of the lung, with cancer cells in it) can potentially be cured.

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.

Thus far, the vast majority of patients who have an initial response to EGFR tyrosine kinase inhibitors like Iressa and Tarceva will eventually become resistant to them.

For many patients with early stage, resected NSCLC, chemotherapy after surgery may be a strong consideration to minimize the chance of the cancer returning, in which cases, it is often not possible to cure it. Several clinical trials over the past few years have shown benefits from chemo combinations, but which ones would be the leading considerations now?

The cornerstone of treating early NSCLC (stage I, II, and sometimes stage IIIA) is surgery, at least if a patient is able to tolerate that. While many patients can be cured after surgery alone, patients remain at risk for both local recurrence near where the original cancer was, and also distant spread. The latter is caused by micrometastases, circulating tumor cells that cannot be detected on scans or blood tests at this time, that can grow to produce visible disease recurrence months or years after surgery.

Although Avastin has been approved for first-line treatment of advanced NSCLC, at this point it cannot be universally employed. Patients with squamous cancers account for something in the range of 30% of patients, while patients with brain metastases amount to about 10-15% of patients. Another 5-10% may have hemoptysis, or the symptom of coughing up blood, and many others are on therapeutic blood thinners for a history of blood clots or atrial fibrillation.

Avastin (bevacizumab), an antiangiogenic agent that works by blocking the blood vessel stimulating factor vascular endothelial growth factor (VEGF), has already been FDA approved and commercially available for colon cancer, but it has now been approved by the FDA for first-line treatment of non-squamous NSCLC in combination with standard chemo of carboplatin and paclitaxel (taxol).