Dear Brian,
Thank you for your thoughtful update. I am so deeply sorry that the Sutent was unsuccessful in stabilizing MJ's disease progression. I am not personally familiar with the new combination EZN-2208 Bevacizumab (Avastin) Phase I Trial at NCI, but I do know that Avastin has unfortunately not been shown to be effective for the ASPS patients who I know that have been treated with it. Also, Avastin used in combination with Cediranib in a Clinical Trial at MD Anderson was heartbreakingly unsuccessful in stabilizing the progression of ASPS patient Patrick Williams disease. Before proceeding with this new Clinical Trial, I urge you to thoroughly research it and to find out from the lead research oncologist in charge of the Trial (is it Dr. Kummar?) if it has shown any success thus far for ASPS patients and what the rationale and research basis are for using this drug combination. I, like Olga, continue to be concerned about MJ still not having had her large primary tumor in her thigh removed, and as I have discussed with you before, I think that the tumor burden created by the large primary may make it difficult/impossible for any systemic treatment to be effective. I personally think that resection of the primary needs to be a priority before proceeding with the EZN-2208 Bevacizumab Phase I Trial at NCI or any other new systemic treatment in order to provide the best chance of a successful response to the treatment and to prevent MJ from having yet another failed treatment response. Please know that my continued most caring thoughts and very best wishes are with MJ and your family, and I will be anxiously awaiting your next update. Please take care Brian and keep in touch with the Board as you are able.
With concern, deepest caring, healing wishes for MJ, and continued Hope,
Bonni
MJ on Cediranib Phase 2 clinical Trial at NCI
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Bonni Hess
- Senior Member
- Posts: 1678
- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Re: MJ on Cediranib Phase 2 clinical Trial at NCI
I have to comment here that despite Avastin being to produce only very short term responses in ASPS and the rapid overgrowth after that, it does not automatically mean that the tested combination will not work. There is now a shift in the med.community in the attitude toward the aniogenesis inhibitors. They were hoped to be the drugs that irreversible damage the tumours blood vessels and shut the blood supply off and now after it was found that these drugs only work for a short time, damage some blood vessels and the remaining ones grow stronger, they expect them to be the adjunct drugs that improve the delivery of the second drug into the tumor. But it is a clinical trial phase 1 so there is really nothing to say about the expected efficacy of this particular combination.
Olga
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Bonni Hess
- Senior Member
- Posts: 1678
- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Re: MJ on Cediranib Phase 2 clinical Trial at NCI
Dear Brian,
Olga has made a very good point regarding the possible advantage of combining an anti-angiogenic drug like Avastin with another drug to provide a more successful and sustained response. My research of the new combination EZN-2208 Bevacizumab (Avastin) Phase I Clinical Trial found the following rationale given for the use of this drug combination:
One reason postulated for the limited efficacy of anti-angiogenic or anti-VEGF agents such as bevacizumab is that they cause intra-tumoral hypoxia, resulting in the induction and up-regulation of hypoxia-inducible factors (HIF) such as HIF-1Alpha. These in turn play a central role in tumor progression by acting as master regulators of how cancer cells adapt to hypoxic conditions. HIF-1Alpha therefore represents an attractive target in oncology.
Camptothecin analogues (including SN-38, topotecan, and irinotecan) have been shown to consistently reduce the translation, expression, and transcriptional activity of HIF-1Alpha in vitro and in vivo, and therefore have the potential to inhibit the HIF-1? induction that occurs with anti-angiogenic agents.
The central rationale of this study is that HIF-1? induction by bevacizumab will be offset by weekly administration of EZN-2208 (PEGylated SN-38), and that this will result in synergistic anti-tumor effects
If MJ decides to proceed with participation in this Trial, please open a new topic for it under the Clinical Trial section where you can update MJ's treatment experience and results. If you have not already read the information about the Trial, or for others on this Board who might be interested in researching more about it, it can be accessed at http://clinicaltrials.gov/ct2/show/NCT01251926
Eligibility requirements for the Trial do state that the patient must not have had a major surgical procedure within the past 28 days prior to beginning the Trial. If MJ decides to have her primary tumor resected she would not be able to begin the Trial until four weeks post-op, so if tumor resection is a consideration she should move forward with it as soon as possible.
With special caring thoughts, healing wishes for MJ, and continued Hope,
Bonni
Olga has made a very good point regarding the possible advantage of combining an anti-angiogenic drug like Avastin with another drug to provide a more successful and sustained response. My research of the new combination EZN-2208 Bevacizumab (Avastin) Phase I Clinical Trial found the following rationale given for the use of this drug combination:
One reason postulated for the limited efficacy of anti-angiogenic or anti-VEGF agents such as bevacizumab is that they cause intra-tumoral hypoxia, resulting in the induction and up-regulation of hypoxia-inducible factors (HIF) such as HIF-1Alpha. These in turn play a central role in tumor progression by acting as master regulators of how cancer cells adapt to hypoxic conditions. HIF-1Alpha therefore represents an attractive target in oncology.
Camptothecin analogues (including SN-38, topotecan, and irinotecan) have been shown to consistently reduce the translation, expression, and transcriptional activity of HIF-1Alpha in vitro and in vivo, and therefore have the potential to inhibit the HIF-1? induction that occurs with anti-angiogenic agents.
The central rationale of this study is that HIF-1? induction by bevacizumab will be offset by weekly administration of EZN-2208 (PEGylated SN-38), and that this will result in synergistic anti-tumor effects
If MJ decides to proceed with participation in this Trial, please open a new topic for it under the Clinical Trial section where you can update MJ's treatment experience and results. If you have not already read the information about the Trial, or for others on this Board who might be interested in researching more about it, it can be accessed at http://clinicaltrials.gov/ct2/show/NCT01251926
Eligibility requirements for the Trial do state that the patient must not have had a major surgical procedure within the past 28 days prior to beginning the Trial. If MJ decides to have her primary tumor resected she would not be able to begin the Trial until four weeks post-op, so if tumor resection is a consideration she should move forward with it as soon as possible.
With special caring thoughts, healing wishes for MJ, and continued Hope,
Bonni