Member Sandra recently asked the question that several other people have asked in one form or another: how do we choose among the treatment options for second line therapy in NSCLC. I've covered in several posts and a huge number of responses in the Q&A Forum the leading options we generally consider for second line therapy for NSCLC.

In my last post I described a new study that will be randomizing previously treated advanced NSCLC patients with a current or prior smoking history to receive either tarceva or a new chemotherapy called pralatrexate. Now it’s time to provide a little background on this new agent.

I've described in a prior post and many of my comments here how tarceva and iressa, oral targeted therapies against EGFR, have been pretty consistently impressive in never-smokers. Not infallibly great, but these agents have shown high response rates in the 25-50% range for never-smokers, and have also been pretty favorable for remote and minimal smokers.

There's a website called Adjuvant! Online, developed by oncologist Peter Ravdin, that is best known for its use after surgery for breast cancer in assessing the value of post-operative chemo. Because I don't really treat breast cancer, I haven't spent time on the website, but I do know that it's a valued resource among practicing oncologists who care for patients with breast cancer.

The antibody to the epidermal growth factor receptor erbitux (cetuximab) (introductory post here) has been used as an effective treatment for colon and also head and neck cancer for several years, but its role in lung cancer has yet to be defined.

As I described in my prior post, the marker ERCC1 (excision-repair cross complementing group 1) is a prognostic variable that is associated with a more favorable survival in patients who aren't treated with chemo after surgery for early stage NSCLC. But this marker also appears to be predictive of resistance to cisplatin and a worse survival in patients treated with platinum-based chemo after surgery.

Although I’ve described this concept in a few posts over the past year, it’s time for me to dedicate some real discussion to the concept of individualizing treatment with the ERCC1 marker. ERCC1 stands for excision repair cross-complementing group 1, and it helps repair damage to DNA.

I wrote about the drug amrubicin in a prior post, after it demonstrated provocative activity in clinical trials out of Japan that were presented at ASCO 2007. Additional result on amrubicin in previously treated ED-SCLC were presented at a NYC meeting last week, and it's continued to look very encouraging in a clinical setting in which we could really use more options.

We've always been tempted to see if we can add more to standard approaches to improve our outcomes. In SCLC, people have attempted to add taxol to cisplatin and etoposide as part of the PET regimen (platinum + etoposide + taxol). Although heavily tested, it clarified that triplet therapy with standard chemo for SCLC appears to be associated with no improvement in outcomes but with a very significant improvement in side effects, including risk of dying from treatment.

We know PET scans can provide additional metabolic information that can be more sensitive and specific for cancer than chest x-rays and even CT scans in the initial staging of lung cancer (see prior post on introduction to PET scans). PET scans are now nearly universally employed in the initial workup, at least of patients who have NSCLC and aren’t already known to have stage IV disease.