Hey all,
Need suggestions for treatment options and supplementation for my brother
His clinical history is-
| clinical history |
date |
remarks |
| diagnosed in |
september 2009 |
assumed to be begnin tumour |
|
|
observation through mri |
| Tumour surgical resection |
18th feb 2016 |
tumour started to enhance in size |
|
|
gross resection of more than 95% |
|
|
tumour size 7.2x5.5x5.1( anaplastic oligoastrocytoma) |
| RT PLUS
CONCURRENT TEMOZOLOMIDE |
2ndAPRIL 2016 TO 17th MAY 2016 |
59.4 gy ,33 fractions plus 120 mg temozolomide |
| Temozolomide |
june 2016 -december 2016 |
6 cycles |
| Recurrence may-18 |
|
|
| reradiation +concurrant temozolomide |
18th jul 18-16th aug 18 |
36gy, 20 fractions plus 120 mg temozolomide |
| temozolomide chemo |
1st jan 19-5thjan 19 |
200mg per day for 5 days |
HIS BIOMARKERS ARE-
| BIOMARKER
AND GENOMIC FINDING |
STATUS |
| MICROSATELLITE STATUS |
MS-STABLE |
| TUMOUR MUTATIONAL BURDEN |
TMB-LOW (4 MUTS/MB) |
| ATRX |
LOSS |
| IDH1 |
R132H |
| NOTCH1 A465T |
SUBCLONAL,E450K-SUBCLONAL,R353C-SUBCLONAL |
| SMARCA4 |
T910M |
| TP53 |
G245S,R273C |
|
|
| MGMT |
UNMETHYLATED(METHYLATION SCORE-0.49) |
| ANTIBODY TYPE |
RESULT |
| GFAP |
POSITIVE |
| IDH1 R132 |
POSITIVE |
| KI-67 |
POSITIVE PROLIFERATIVE INDEX APPROX 10-15% |
|
|
| FISH TEST |
|
| 1P/19Q CO-DELETION |
NEGITIVE |
| EGFR |
NEGITIVE FOR EGFR AMPLIFICATION |
| PTEN LOSS |
POSITIVE (39.3% OF NUCLEI EXAMINED) |
His current medications are-
| Part of
Day |
Medicine Name |
Medicine count |
Notes |
| PRE MORNING |
BROMELAIN 500 MG NOW |
3 |
EMPTY STOMACH |
|
TAB PAN 40 MG RT OD |
1 |
STOP ON 30TH JAN 2019 |
| MORNING BREAKFAST |
CURCUMIN TABLETS |
3 |
NOT WITH AVASTIN OR TAGRISSO/TARCEVA |
|
GLYCEROL 30 ML |
1 |
|
|
DIAMOX 250 MG |
1 |
|
|
METAFORMIN 500MG |
1 |
TWICE DAILY FROM 1ST FEB |
|
IBUPROFEN 200 MG |
1 |
|
|
CBD OIL 2 FULL DROPPERS |
1 |
|
|
LEVIPILL 750 MG RT |
1 |
|
|
LASILACTONE 20/50 MG RT |
1 |
|
|
TAB DEXA 4 MG RT |
1 |
STOP AFTER 21ST JAN |
|
TAB BACLOFEN 5MG RT |
1 |
|
|
REFRESH EYE DROP |
2 |
BOTH EYES 2 DROPS |
|
LEVOLIN NEBULISATION .63MG |
1 |
STOP ON 25TH JAN 2019 |
|
TAB GLYCOPYRROLATE 1 MG |
1 |
STOP ON 20TH JAN |
| TO BE ADDED |
VALGANCICLOVIR 450 MG |
2 |
|
|
CHLOROQUINE 250 MG |
1 |
|
|
CELEBRAX 200MG |
1 |
|
|
WHEY PROTIEN |
2 SCOOPS |
WHEN RECD FROM USA |
|
GRAPESEED EXTRACT 250 MG |
1 |
|
|
STRESS B COMPLEX |
2 |
|
| LUNCH |
CURCUMIN TABLETS |
3 |
|
|
MEBENDAZOLE 100 MG |
1 |
START DOXYCYCLINE ON 18 TH APRIL |
|
GLYCEROL 30 ML |
1 |
|
|
IBUPROFEN 200 MG |
1 |
|
|
LASIX 40 MG |
1 |
|
|
REFRESH EYE DROP |
2 DROPS |
STOP AFTER 21ST JAN |
|
LEVOLIN NEBULISATION .63MG |
1 TIME |
STOP ON 25TH JAN 2019 |
|
TAB GLYCOPYRROLATE 1 MG |
1 |
STOP ON 2O TH JAN |
| TO BE ADDED |
CELEBRAX 200MG |
1 |
|
| NIGHT |
CURCUMIN TABLETS |
3 |
|
|
ATORVASTATIN 40 MG |
1 |
80 MG FROM 1ST FEB |
|
GLYCEROL 30 ML |
1 |
|
|
DIAMOX 250 MG |
1 |
|
|
IBUPROFEN 200 MG |
1 |
|
|
CBD OIL 2 FULL DROPPERS |
1 |
AFTER HALF HOUR GIVE THC 6 DROPS |
|
THC OIL 6 DROPS |
1 |
|
|
LEVIPILL 750 MG |
1 |
|
|
LASILACTONE 20/50 MG |
1 |
|
|
TAB BACLOFEN 5MG RT |
1 |
|
|
REFRESH EYE DROP |
1 |
BOTH EYES |
|
LEVOLIN NEBULISATION .63MG |
1 TIME |
STOP ON 25TH JAN 2019 |
|
TAB GLYCOPYRROLATE 1 MG |
1 |
STOP ON 2O TH JAN |
| TO BE ADDED |
VALGANCICLOVIR 450 MG |
2 |
STOP ON 9TH FEB 2019 |
|
CELEBRAX 200 MG |
1 |
|
|
BERBERINE 500 MG |
1 |
|
| BEDTIME |
ARTEMISIA 500 MG |
2 |
WHEN RECD FROM PATRICE |
|
TAB FRISIUM 5MG RT |
1 |
|
PLEASE SUGGEST
1.SUPPLEMENTS TO ADD OR TO BE DISCONTINUED
2.AVASTIN OR LOUMUSTINE OR ANY OTHER TRIAL DRUG BEST SUITED FOR HIM
3.ANY OTHER EFFECTIVE THERAPY TO HELP HIS QUALITY OF LIFE. |
|
|
Sushant .. stopping DEXA from 4 mg to zero concerns me .. it should be slow .. We did it as told by doctor and ended up in ER .. can you talk with your NO about tapering it ..
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteThanks for suggestion yogesh..i will keep in mind.
ReplyDelete@stephan .. can you suggest something?
ReplyDeleteHi Sushant,
ReplyDeleteThis drug list is fairly lengthy and it's not clear to me which of these drugs he needs to be on for other indications, and which are part of his anti-tumor cocktail. I could make educated guesses but don't want to assume too much. In particular, Diamox (acetazolamide), Lasilactone, baclofen, Levolin, glycopyrrolate, Lasix - does he have prescriptions for these for other reasons? Could you list the drugs/supplements that are specifically part of his anti-tumor cocktail. I assume that is the case for valganciclovir, chloroquine, Celebrex, and it also looks like you're emulating the Care Oncology protocol (metformin, doxycycline, atorvastatin, mebendazole).
If you don't see any improvements on his next MRI under temozolomide treatment, I would consider trying a round of lomustine. A tumor that has developed resistance to TMZ may still be sensitive to lomustine. However, the benefit for both of these drugs may be limited by his unmethylated MGMT status, but it's probably worth giving lomustine a try for one cycle if his blood counts are holding up.
I will try to look into clinical trials he might be eligible for as well. What part of the world is he in/ city where he's getting treatment?
Hey stephan,
ReplyDeleteHe had spasticity in weaker side of body as a result his right hand becomes stiff and right leg starts to shake and unreasonable sweating starts with high pulse rate and doctors started all these medication like beclofen,lasilactone,levolin,glycopyrollate and lasix plus 1 week of dexamethasone all other medications were started 5 days ago for tumour treatment.he got tracheastomy done 2 weeks ago due to weak cough reflex abd thus caught infection with tlc of 21000 but recovered to 10000 tlc count,but since then he has been really weak and drowsy.would loumustine be good choice with symptons or avastin?.
We are based in new delhi,india but we are willing to travel to any site suitable for his treatment .
Hi Sushant,
DeleteI wrote out a fairly lengthy comment with clinical trial ideas, but it didn't post properly and I lost the comment, so here it is again a little more briefly.
1. Lomustine with or without eflornithine, a randomized phase 3 trial in the USA, Canada and Europe.
https://clinicaltrials.gov/ct2/show/NCT02796261
Unfortunately this is randomized, so it is a long way to travel for a trial where he might be assigned to lomustine alone. The trial isn't blinded so you would know which arm he'd been assigned to. There was an earlier trial published in 2003 showing good results with the addition of eflornithine to chemo, which makes this new trial interesting.
2. PARP inhibitors. IDH-mutant tumors may have an especial sensitivity to PARP inhibition. There are several trials underway testing the approved drug olaparib in high grade gliomas. Since olaparib is already approved he might be able to get access in India, though I'm not sure how costly or difficult this would be.
Another PARP inhibitor in clinical trials is called BGB-290 and may be better than already approved PARP inhibitors in terms of blood-brain barrier permeability. It is in trial in the USA, Canada and in Australia.
https://clinicaltrials.gov/ct2/show/study/NCT03749187 (ages 13 - 25 only)
https://clinicaltrials.gov/ct2/show/NCT02660034 (Australia)
3. Trials in the USA testing several different inhibitors of mutant IDH1
https://clinicaltrials.gov/ct2/show/NCT03343197 (this trial also requires a surgery)
https://clinicaltrials.gov/ct2/show/NCT03684811 (IDH1 inhibitor with or without 5-azacytidine)
These drugs are likely most effective in tumors in the earlier stages of evolution (grade 2) and less effective in more advanced stages when the tumors have picked up new driver mutations and are less dependent on mutant IDH1.
4. Approved hypomethylating agents such as 5-azacytidine. IDH1-mutant tumors typically have pathological levels of DNA methylation, causing epigenetic disruption and silencing of cell differentiation and tumor suppressor genes. This provides the rationale for using drugs like 5-azacytidine in these tumors. This strategy will go into human trials in France later this year
https://clinicaltrials.gov/ct2/show/NCT03666559
Like olaparib, 5-azacytidine is an already approved drug for another type of cancer, so could be prescribed off-label outside of a trial if you could find a willing oncologist.
5. VAL-083 (chemotherapy). Unlike TMZ and lomustine, which have MGMT-dependent mechanisms of action, VAL-083 has an MGMT-independent mechanism, so should work equally well in MGMT methylated and unmethylated tumors. This is available in an expanded access protocol outside of a trial, though I'm not sure which countries this applies to.
https://clinicaltrials.gov/ct2/show/NCT03138629
6. Finally, one last trial idea would be an antibody against DLL3, which is typically highly expressed in IDH1-mutant tumors. See my prior blog post:
http://btcocktails.blogspot.com/2018/11/rovalpituzumab-tesirine-dll3-antibody.html
and the link to the clinical trial recruiting in the USA
https://clinicaltrials.gov/ct2/show/NCT02709889
7. Retinoic acid drugs such as Accutane or all-trans retinoic acid (tretinoin, ATRA), may have some use in IDH1-mutant tumors, but I wouldn't combine them with chemotherapy as they could interfere with chemo.
http://btcocktails.blogspot.com/2018/12/retinoic-acid-for-reversing-immune.html
@stephen .. really appriciate your help. Thanks
ReplyDeleteHi Sushant.
ReplyDeleteMy brother is also undergoing the treatment for the same type of tumor. And he is currently based in Delhi, India while I live in the states. Please reach out to me if I can be of any help.
Regards
Surbhi