During the entire time I've been commenting on the most evidence-based and commonly used agents for previously treated patients, I've focused on taxotere, alimta, and tarceva (example in prior post here). In fact, that overlooks an agent that has actually been tested in a large study and been found to have similar activity to taxotere, but it remains pretty much an afterthought.

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 the Q&A forums recently, members Jianming and Neil introduced us to the novel agent XL647, in clinical trials now, but I figured it was worth me collecting more background and providing a more thorough background. XL647 is an oral small molecular that inhibits multiple tyrosine kinases, receptors on cells that trigger cascades of activity in the cells, thereby leading to tumor development and growth.

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.

Intuitively, you'd think that people who are doing worse while getting treated for lung cancer are not going to do as well as people who have improvement in their symptoms after treatment starts. But how much do patient symptoms count in our current medical system for deciding whether a treatment is working or not, and when to move to a new therapy? The answer is that patient reported symptoms don't have a clear role yet.

This bit of news slipped under the radar for the past six weeks, but oral topotecan was approved by the FDA for the treatment of SCLC that has recurred at least 45 days after the last chemotherapy had been given. I'm a little embarrassed to say that I hadn't noted this, but it really got very little airplay. Part of it is that topotecan was already available and approved for recurrent SCLC in its IV form.

In a post several months ago, I described the results of a trial from Japan, designated V-15-32, that directly compared Iressa to Taxotere as a second line therapy. Although overall comparable, the study showed that Japanese patients receiving Iressa had a higher response rate, but despite that had a lower median and one year survival.

Let's move to combinations of velcade with other anti-cancer agents. My friend, Dr.Angela Davies from the University of California at Davis, led a single-arm phase II trial conducted by the Southwest Oncology Group, SWOG 0339, that evaluated the combination of velcade with gemcitabine and carboplatin (abstract here).

Our tendency in oncology is that once we find a new active drug in cancer, we try to add it to our current standard treatment approach and see if we can do better than what our current standard achieves. More is better. And we knew that the epidermal growth factor receptor inhibitors Iressa and Tarceva could lead to significant shrinkage of some lung cancers. So the lung cancer community was relatively optimistic about the clinical trials that compared chemo alone to the same chemo with Iressa or Tarceva.