My brother has been doing TMZ 5/23 for over 18mths. We are wondering about changing the dose to daily low dose to try and avoid the fatigue etc that he has for that week. Would low dose be as effective? He is MGMT methylated.
Thanks, Lisa
Hi Lisa, Please see the Treatment Options update in the post above this one, especially the "How many cycles of TMZ?" section. One study showed that 12 cycles of TMZ led to significantly longer progression-free survival versus 6 cycles, but a second study failed to show a benefit of going beyond 12. A metronomic schedule could conceivably benefit given the overexpression of EGFR in his tumor. However the standard metronomic schedule (50 mg/m2/day) is also hard on lymphocytes.
I've mentioned this study frequently lately, but here is the link again. http://meetinglibrary.asco.org/content/151704-156
See also the section on beta-blockers (esp. propranolol) in the new 2016 treatment options update.
The standard metronomic dose (50-75 mg/m2 or about 80-100 mg daily) is hard on lymphocytes. Very low dose TMZ (eg 20 mg twice daily) would not be, and would also not likely have any direct effect on the tumor either, but would be selectively toxic to immune suppressor cells, which is a good thing in combination with immunotherapies.
Lymphocytes include CD4+ and CD8+ T-cells, which are responsible for the adaptive, anti-cancer immune response. For that reason I wouldn't suggest combining standard dose metronomic schedule (50 mg/m2) with immunotherapy.
Hi Lisa,
ReplyDeletePlease see the Treatment Options update in the post above this one, especially the "How many cycles of TMZ?" section. One study showed that 12 cycles of TMZ led to significantly longer progression-free survival versus 6 cycles, but a second study failed to show a benefit of going beyond 12. A metronomic schedule could conceivably benefit given the overexpression of EGFR in his tumor. However the standard metronomic schedule (50 mg/m2/day) is also hard on lymphocytes.
I've mentioned this study frequently lately, but here is the link again.
http://meetinglibrary.asco.org/content/151704-156
See also the section on beta-blockers (esp. propranolol) in the new 2016 treatment options update.
Thanks Stephen. So are you saying the lower daily dose is hard on lymphocytes?
ReplyDeleteThe standard metronomic dose (50-75 mg/m2 or about 80-100 mg daily) is hard on lymphocytes. Very low dose TMZ (eg 20 mg twice daily) would not be, and would also not likely have any direct effect on the tumor either, but would be selectively toxic to immune suppressor cells, which is a good thing in combination with immunotherapies.
ReplyDeleteWhat are the issues of lowering lymphocytes?
ReplyDeleteLymphocytes include CD4+ and CD8+ T-cells, which are responsible for the adaptive, anti-cancer immune response. For that reason I wouldn't suggest combining standard dose metronomic schedule (50 mg/m2) with immunotherapy.
Deletehttp://www.ncbi.nlm.nih.gov/pubmed/21737504