We’ve been following sorafenib (nexavar), a multi-kinase inhibitor with anti-angiogenic activity (see prior post). This oral agent, which is already approved as an effective treatment for cancers of the liver and kidney.

Last week, the preliminary results of interim analysis the ESCAPE (Evaluation of Sorafenib, Carboplatin, And Paclitaxel Efficacy in NSCLC) trial were presented by Dr. Scagliotti at the 1st IASLC (International Association for the Study of Lung Cancer)-ESMO (Eurpean Society for Medical Oncology) Lung Cancer Conference in Geneva, Switzerland. This was a randomized, placebo-controlled, double-blind phase III study for patients who have not yet had chemotherapy for advanced NSCLC.

One of the novel agents being studied in lung cancer is sutent (sunitinib), a multi-targeted oral anti-angiogenic drug that I’ve described in a prior post.

There's been several discussions about the potential value of maintenance therapy after the initial chemotherapy for SCLC; I've discussed this subject in a prior post, in which I focused on chemo -- while the results haven't been strong enough to lead to a change in standard practice, at least one trial showed a strong trend in the right direction.

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.

Several trials have recently opened up for never-smokers with any lung adenocarcinoma or those with BAC (or adeno/BAC mix, invasive adenocarcinoma with BAC features) with any smoking status. Both of these groups have only recently gained recognition as likely being a distinct clinical entity with a different natural history (clinical behavior outside of treatment) and pattern of responsiveness to treatments that is different from other types of lung cancer.

As introduced in the last post, ZD6474, or Zactima, is a pill that blocks tumor blood supply and at higher doses (in the 300 mg per day range) also blocks EGFR. This mutli-targeted therapy has shown some intriguing activity when combined with chemo, and today I'll focus on the research that gave it as a single agent and where it has led us in terms of current trials.

In prior posts I've described the idea of combining targeted agents like Tarceva and Avastin, but there are also some single agents that inhibit multiple targets within cancer cells. I've described sorafenib/nexavar in a prior post. Today I'll focus on another multi-targeted agent, known previously as ZD6474, and with a marketing name of Zactima. Similar to the combination of avastin and tarceva, this single oral drug is anti-angiogenic and also blocks EGFR. Although less well studied, it also blocks a protein called RET and can inhibit cell proliferation that way.