Sunday, 20 January 2019

Recurrant anaplastic astrocytoma treatment options

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.

8 comments:

  1. 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 ..

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  3. Thanks for suggestion yogesh..i will keep in mind.

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  4. @stephan .. can you suggest something?

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  5. Hi Sushant,
    This 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?

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  6. Hey stephan,
    He 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 .

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    1. Hi Sushant,
      I 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

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  7. @stephen .. really appriciate your help. Thanks

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