XL647: Novel Agent As An Alternative or Follow-up After Tarceva

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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.

ERCC1 in Advanced Lung Cancer

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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.

Comparison of Iressa to Single Agent Chemo in First Line treatment for Elderly Advanced NSCLC Patients: The INVITE Trial

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In addition to a direct comparison of iressa to chemo in the second line setting for advanced NSCLC (see recent post on INTEREST trial), as conducted with the INTEREST trial I described in a recent post, a very similar comparison of Iressa to chemo was also performed in another setting where single-agent chemo is also the treatment of choice. Specifically, the INVITE trial evaluated iressa vs.

The INTEREST Trial of Chemo vs. Iressa as Second Line Treatment for Advanced NSCLC

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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.

Is There a Better Way to Combine EGFR Inhibitors and Chemo? The Concept of Pharmacodynamic Separation

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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.

Is there a Group That Does Particularly Well with Erbitux in NSCLC?

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I wrote in a post several months ago about the ongoing study of the monoclonal entibody against EGFR erbitux (cetuximab) in lung cancer, where it's role is still up in the air. Unlike the EGFR tyrosine kinase inhibitors (TKIs) iressa and tarceva, which showed no benefit when given concurrently with standard chemo, erbitux has a different mechanism and may still be useful when given along with chemo.

Trial of Chemo with or Without Erbitux in Advanced NSCLC Negative

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It's a little sad that you can get more cancer information from the business websites than from the medical ones, but if you checked a story on Forbes.com today you learned that Bristol-Myers Squibb (BMS) provided a press release that one of their important Erbitux (cetuximab) trials didn't meet its primary endpoint of improved progression-free

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