Many studies have compared 6 cycles of monthly temzolomide to extended temozolomide for newly diagnosed GBM. However, all of those studies have been retrospective in nature (they were not designed as prospective clinical trials randomizing patients to either 6 or 12 months of monthly TMZ).
A small (20 patients in each arm), but randomized trial was published recently by an Indian group. The result was a 4 month increase in median progression-free survival in the 12 month arm, and a >8 month increase in median overall survival (15.4 months versus 23.8 months), measured from diagnosis.
Patients in this trial were between the ages of 18 and 65, with KPS equal to or over 70. Unfortunately, there was no information (and consequently no stratification by) MGMT status, which limits the significance of the study, as the authors readily admit. "One limitation of our study is the small sample size of patients
and lack of information on MGMT methylation status of patients." However, this is the first randomized trial for newly diagnosed GBM comparing 6 cycles to 12 cycles of monthly temozolomide treatment.
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Hi Stephen, based on your research to date - do you have an opinion on whether you would stop after a specific amount of monthly TMZ cycles or keep using it up to 12 cycles and on?
ReplyDeleteI know it is likely a case by case basis as in my Dads case he is MGMT methylated so we have faith in TMZ but it gets tougher each month on him. Our thoughts our keep using it (at 6 cycles now) until images show it is no longer preventing tumor growth...?
Here is a previous post on this blog discussing this. Curious if you have any updated opinions?
http://btcocktails.blogspot.com/2016/02/tmz-cycles.html#comment-form
Thanks for everything and have a great weekend.
I think my decision would be based mainly on 1) MGMT status 2) tolerability and 3) whether or not treatment with a vaccine were within my financial means.
DeleteGiven that prolonged TMZ tends toward cumulative toxicity to the bone marrow and blood counts, if vaccine treatments were within my means I would probably monitor lymphocyte counts carefully and transition to immunotherapy before the counts dropped too low. If vaccines are not an option, and with MGMT methylated status I would probably continue as long as there seemed to be a benefit and reasonable tolerability, certainly up to 12 months or more.
Hi Stephen:
ReplyDeleteI would like to revisit this topic of how many TMZ cycles. My husband is 77 yrs. Had his first GBM4 tumor Aug 2013. Tolerated the TMZ fairly well for a year. Had recurrence Jan 2018. Both methylated tumors fully resected. Hubby just completed TMZ round#7. Blood counts holding stable. Our NO, whose advice I normally don't put a lot of stock into, suggests stopping at round#12. Our second opinion NO at UCSF, who I think is brilliant, suggests stopping TMZ if next MRI in Sept is still stable. She feels whatever good it does happens in the first 6 mos.
I reviewed http://btcocktails.blogspot.com/2016/02/tmz-cycles.html#comment-form
Is there any "updated" info on any studies on this topic? Also, what vaccines are at the top of your list?
As always, thank you and everyone so kindly.
Best to you,
Candy
Stephen I just found your Aug 18, 2018 post referring to the 2017 study so no need to reply about updated studies.
ReplyDeleteIn the 2019 ASCO abstracts, there is a report of the results of a randomized trial where patients were randomized to continue an additional 6 cycles of TMZ or not continue TMZ after successful completion of the first 6 cycles.
ReplyDeleteThis trial was more advanced than the Indian trial reported in the post above, as it was stratified by MGMT status.
80 patients were randomized to an additional 6 cycles, and 79 patients were randomized to no additional TMZ cycles.
Surprisingly, no difference in median PFS was observed between the arms (HR = 0.98, p = 0.907), seemingly showing no benefit of extending TMZ cycles beyond 6.
I would still like to see the breakdown for the MGMT methylated patients specifically though.
https://abstracts.asco.org/239/AbstView_239_260615.html