Monday 23 October 2017
Temodar and CCNU
We finally convinced our NO to give our son Temodar and CCNU for his recurrence. Our NO wants to do it every 42 days. However, we are uncomfortable with such long gaps, especially considering his platelets are good. Do you know of any studies with shorter periods between administration that I can refer our doctor to? Thank you !
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There is so much history of using CCNU on a 6 week schedule and before that using BCNU also on 6 week schedule, that it seems very unlikely that an NO would approve to do it on a shorter cycle. Added to that is the NA09 phase 3 trial results that was done with TMZ plus CCNU on 6 weeks and it would be even more 'out there' for an NO to approve a faster cycle.
ReplyDeleteAlso note that CCNU is in general much harsher on blood counts than TMZ. They both knock down platelets, but also neutrophils. CCNU actually kills stem cells so it is not a temporary drop, but more of a ratcheting down over time.
The other thing to consider is that both drugs are less effective at lower dosages and it is very common to have to reduce dosage with CCNU due to blood counts. So doing the combo AND shortening the cycle would make it very likely your NO would have to significantly lower the dosage thru the rounds which would likely make the treatment less effective than sticking to the 6 week cycle.
So overall it might be better to focus on the other tools discussed on this board for improving chemo effectiveness.
Thank you so much for your really informative reply! it make perfect sense.
DeleteJust a side note, since chemo is hard on platelets...Aren't there also some supplements that help keep platelets up? I didn't have chemo so haven't researched it much...but if I remember correctly, some people recommended PSK, enough protein and iron. I think I saw chlorella and spirulina mentioned a lot.
ReplyDeleteMy Dad's been taking PSK (coriolus versicolor) for more than a year now. It has really helped with his platelets. Before that his platelet count used to drop really low and he had to get transfusions. I think it's definitely worth a try!
DeleteWe recently switched from TMZ to TMZ/CCNU on the back of the promising NOA-09 results (8th cycle, we continue with medical treatment after completion of SoC). Blood counts will be the potential limiting factor going forward. However, our NO said that we could continue earlier than the typical 42 day cycle (probably 35 or even 28 as with TMZ) if blood count allows for this. So this is clearly up you / your NO, as there is no standard therapy in case of a recurrence.
ReplyDeleteThank you! that was my thinking - see how platelets react first and be aggressive if blood counts allow.
DeleteMalte thats good to know that some NO's will 'short cycle' CCNU. Would be useful to hear how that goes in terms of blood counts.
ReplyDeleteOlga, with low methylation of it is probably more important to focus on getting the chemo to 'hit harder' vs faster. You basically have to overload the repair mechanisms in the cell. Unfortunately that generally will come at a cost of deeper drops in blood counts. Was platelets the main issue with the previous rounds of TMZ? CCNU will generally drop neutrophils (white cells) a lot more than TMZ would have.
The ideal would be to take steps to increase penetration and residence time of the chemo without increase time in the blood stream. Nothing does that perfectly, but see the BBB section of astrocytomaoptions.com. Stuff like verapamil or viagra could be useful, but would be hard to do without NO support.
As a side thought, since you had done immune therapy, is it pretty confident that this is real progression and not psuedo progression?
Thank you so much! Unfortunately, yes, they are sure - it was outside of the original tumor bed , so they excluded pseudo progression - I was very hopeful at first.
DeleteI am meeting our NO on Friday, but I think I can probably get the meds you mentioned without him ( mailed to me from Europe). Thank you so much again!
The reason to involve and NO is both because of the added risks of drug interactions, some added myelo suppression, but also because some of them like viagra/cialis only work for a few hours and need to be timed with CCNU to get any benefit. They also cause blood pressure drops and so sort of 'pretesting
ReplyDelete' before chemo would make sense.
Oh, I see what you mean . I am sure our NO will be completely against this
ReplyDeleteOlga I'm not saying its impossible to go it alone without NO consent, just harder and it elevates the risks some.
ReplyDeleteIf you setup a couple options to increase chemo penetration and residency time, plus attempts to downregulate MGMT (like increasing keppra dosage around chemo time), then start with the safest combo and do the first round. If his counts are ok then be more aggressive round 2.
That also gives you a little time to investigate the options and ask questions on the forum.
Thank you! We are on 2000 of Keppra to control seizures - do you think it could be upped to a higher dose around chemo? Also, we gave him accutane right before the first chemo - do you think it makes sentence to do it again before the second round? Thank you so much again!
DeleteBe careful with Accutane (isotretinoin). When combined with chemotherapy it has the potential to produce outcomes that are not as good as chemotherapy alone, according to this clinical trial:
Deletehttps://www.ncbi.nlm.nih.gov/pubmed/25239666
"Compared with ddTMZ, the ddTMZ + isotretinoin doublet had worse PFS (10.5 vs 6.5 months, P = .043) and OS (21.2 vs 11.7 months, P = .037)."
Ever since this trial was published I have thought of Accutane as something that could still be helpful as a maintenance therapy, but not necessarily something to combine with chemotherapy.
On the other hand, a tumor that is resistant to chemotherapies like TMZ and CCNU still has a chance of responding to something like Accutane, so it's probably worth a try if chemo seems to be ineffective.
For Keppra, 2000 total or 1000mg bid (bi-daily, ie 2x a day) is a middle range dose. The typical min dose for glioma is 500mg bid and a high range is 1500 bid, though higher is certainly not unheard of. It is generally considered a 'clean' drug that has minimal interactions so is generally safe.
DeleteOne complication though is the improvement in outcomes is definitely not proven or understood yet. Some studies showed you need P53 + HDAC which is then the link to mgmt suppression. So mutated/silenced p53 may break the mechanism that keppra has to reduce mgmt.
I'd say its in the category of 'it might help and seems unlikely to hurt'.
My son (50) has AA3 diagnosed 10 years ago, 2 craniotomies, no RT, no chemo until last year. After the 2nd surgery he would have 4-6 heavy seizures per month. They were manageable because there were precursors a few minutes prior to onset. The week of Nov 8, 2015 he had flurries of lighter seizures (30-40/day). Someone told us about CBD oil which we were able to get it on Friday of that week. He started taken it that evening and hasn't had a seizure since then, this November will mark 3 years.
DeleteWe were told that several hospitals are now recommending CBD oil for seizures. There's a ton of anecdotal evidence and more and more news reports monthly.
He takes a tincture of 20:1 (CBD:THC), half a dropper sublingual 3X/day.
Hope this can help. No possibility of overdosing, and there is no evidence of contraindication with any other medications.