Quote:
Cytotoxic anticancer drugs (topotecan, vinorelbine, melphalan, doxorubicin, cisplatin) antagonize the ability of Avastin to kill endothelial cells through this specific cell death mechanism. The standard, traditional cytotoxic drugs all inhibited Avastin, but the new, "targeted" drugs either don't inhibit it or actually enhance it (e.g. lapatinib, erlotinib).
Clinical trials have shown that the combination of chemotherapy with Avastin generally works better than either alone (that is, in situations where Avastin works at all). But this is because Avastin has a very long half life (weeks) and it has the opportunity to work at times when the drug levels of the standard anticancer drugs go down to undetectable levels (where they won't antagonize the ability of low VEGF to cause death of the tumor endothelial cells).
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Potentially HUGE ramifications here. Essentially..the traditional maximum tolerated dose approach of most standard chemos schedules may be undoing Avastin. Roche should be all over this like roaches on..just pick something.
But it does seem to me the metronomic combination of daily Cytoxan with Avastin has not proved to be a winner.
The cellular calcium overdose issue is intriguing since I believe Tamoxifen has that as part of its numerous mechanisms. I bet very few have paired Avastin with Tamoxifen or other hormonals. Tamoxifen crosses the blood brain barrier too.