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New study details potential for fast tumor growth after stopping Sutent

Posted by on May 10, 2012 in RCC News & Research - 7 Comments
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Below is a pretty technical abstract of a new study detailing what we might call Boomerang Effect of using TKI drugs like Sutent. Cancer cells need nutrients to grow. They get such nutrients by a process known as angiogenesis — in which they grow blood vessels to connect with the blood stream (where nutrients are circulated). Angiogenesis inhibitors block this process, thereby blocking this process and starving tumors. The problem with these drugs is twofold:

  1. Eventually the tumors get around the drug, finding new ways to develop blood vessels. (TKIs target VEGF a protein that promotes angiogenesis. However, there are other proteins that can promote angiogenesis, and eventually the cancer cells — which seem to be psychotically clever — find these alternative pathways.) This is why Sutent, for example, has a media eleven-month progression-free-survival rate.
  2. Once a patient goes off the drug, there is a boomerang effect — the cancer cells redouble their angiogenesis efforts. It’s like they are making up for lost time. The result can be faster tumor growth.

This is one reason Dena and I have tried to keep TKIs in our back pocket as a last recourse. I have been lucky in that I’m young and healthy enough (other than this whole cancer business) that I have been able to experiment with different therapies first. Dena and I have focused on immunotherapies like IL-2, MDX-1106 and IL-15 in the hopes of finding a treatment that sparked the body’s own immune defenses to fight the cancer. This promises the hope of fighting the cancer long-term, as opposed to a drug that we know will eventually cease working and may in fact cause enhanced progression after it does stop.

Purpose: To investigate the angiogenic changes in primary tumor tissue of renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor (VEGF)-targeted therapy. Experimental design Phase II trials of VEGF pathway targeted therapy given prior to cytoreductive surgery were performed with metastatic RCC patients with the primary tumor in situ, to investigate the necessity of nephrectomy. Primary tumor tissues were obtained and assessed for angiogenesis parameters. Results were compared to similar analyses on untreated tumors. Results Sunitinib or bevacizumab pretreatment resulted in a significant reduction of microvessel density in the primary tumor. Also, an increase in vascular pericyte coverage was found in sunitinib-pretreated tumors, consistent with efficient angiogenesis inhibition. Expression of several key regulators of angiogenesis was suppressed in pretreated tissues, among which VEGFR-1 and -2, angiopoietin-1 and -2 and PDGF-B. In addition, apoptosis in tumor and endothelial cells was induced. Interestingly, in sunitinib-pretreated tissues a dramatic increase of the number of proliferating endothelial cells was observed, which was not the case in bevacizumab-pretreated tumors. A positive correlation with the interval between halting the therapy and surgery was found, suggesting a compensatory angiogenic response caused by the discontinuation of sunitinib treatment.

Conclusion: This study describes for the first time the angiostatic response in human primary renal cancers at the tissue level upon treatment with VEGF targeted therapy. Discontinuation of treatment with tyrosine kinase inhibitors leads to accelerated angiogenesis. The results of the current study contribute important data to the ongoing discussion on the discontinuation of treatment with kinase inhibitors.

You can read the full article: Rapid angiogenesis onset after discontinuation of sunitinib (Sutent) treatment of renal cell carcinoma patients

  • Jplantin

    That’s depressing. On sutent one year today. I thought you were on sutent earlier this year. Hopefully the IL 15 is working for you.

    • Deb

      Note that the study refers to primar tumors, not distant mets. Definitely have heard of the rebound effect but have not seen this personally. Stopped Nexavar (TKI) after 15 months and no rebound.

      Interestingly, just stopped another trial drug, another anti-angiogenesis drug that I was on 3 years. Took a full 3 months off… And tumors have actually shrunk a bit.

      So…each person responds individually. The immune system is an amazing thing.

      • Chris Battle

        Thanks for the update, Deb. As always, there is nothing certain about cancer — and it’s good to see personal examples like yours!

    • Chris Battle

      Nothing is certain, so don’t let this get you down. The fact that you’ve been responding to Sutent for a year is in itself fantastic news. I know folks who have been on the drug for years. Statistics are only statistics. New treatments are coming to market on a regular basis, too. Just think — about seven years ago, Sutent wasn’t even an option! (Yes, I was on Sutent earlier this year; unfortunately, it didn’t really work for me.)

  • Minniekriek

    This abstract made me think of an expression, “to learn from experience is generally to learn what you don’t wish to know.” This IS a very technical extract and sadly… I understand it because I might well be there someday!!

  • Teresausas

    Sutent gaves almost 4 years of life to my husband, after then he went on to Nexavar and Interferon and he had two more years, with big efforts and figthing.  It was his only hopeand he took it.

  • Erin Oliver

    Um… I know you’re busy and all being Lucky Patient # 13, but this kind of intermission betwixt posts makes me nervy.
    No pressure.

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