Accelerated Metastasis after Short-Term Sutent

[Olga]

Cancer Cell, Volume 15, Issue 3, 232-239, 3 March 2009
http://www.cell.com/cancer-cell/abstrac ... 09)00029-4
Summary

Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible metastatic conditioning in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.

[Fictional]

These are kind of strange results especially as now there is considerable experience with anti-angiogenesis inhibitors in human beings (this study is a mouse study). It certainly is an important caution, but to my knowledge, this has not been observed in people. It is possible some of these changes can be seen with very long-term angiogenesis inhibition treatment, but I think some patients have been taking Sutent for years now.

Also because of the way the abstract is worded, I'm not sure what cancers had accelerated metastases. I don't have access to the full report.

'K' was on Sutent for 6 months. She had no growth in her primary but some tiny lung nodules grew toward the end of the 6th months. She has now been off Sutent for almost a year and a half. If you were to ask me, I think Sutent slowed growth a little in the lung nodules (but unfortunately not completely). The largest growth in the mets was seen after the primary was removed (this has been reported by other patients too...though that the primary has some inhibitory effect on metastases...sort of like competition between primary and secondary tumors) and she was off Sutent.

'K' was on the 3 weeks on, 1 week off cycle of Sutent, and we had the feeling it would have been better to just be on a lower dose every day, which is how many are prescribing it now.

Rebound angiogenesis may be a significant factor in ASPS with any chemo agent (why rebound growth is seen after AIM, rapamycin, etc.). I've gotten the feeling that rebound is less acute with metronomic therapy - one wonders whether switching to a weaker agent (like Celebrex) after the bigger guns might prevent rebound, but preserve benefit. From one of Amanda Minderlein's posts about Vinblastine and Celebrex, she mentioned her oncologist decided to keep her on the Celebrex after going off Vinblastine to avoid stressing her system. Maybe that was a good idea. As I remember, she took Celebrex for another couple of months, then went off it.

[Olga]

'F' - I am very confused as well and I guess I am not alone here, there are a few articles that published at the same issue of the Cancer Cell that are on the same subject and are very worrisome with the reviews of the recent clinical trials results in human and it again rises the question of not publishing the results of the other clinical trials, may be you will be able to find full texts and look trough these are articles

http://www.cell.com/cancer-cell/issue?p ... 09)X0003-6

There is a huge resonance now all over the press and the internet about these new publications.