Treating Ascites with Angiogenesis Inhibitors

Malignant ascites are side effects of some cancers (and potentially anti-cancer treatments), characterized by the accumulation of fluid in the abdomen.

Recently, I have received from a friend this article on ascites (from epithelial ovarian cancer), and thought is a good idea to share this here: Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675660/#SD1

According to this article, I understand that effective treatments against the ascites are focused on angiogenesis inhibition addressing the following:

1. VEGF inhibition

2. inhibitors of the tumor-promoting tumor-associated macrophages (TAM) commonly designated as “M2”

Here are some VEGF inhibitors I know (besides the conventional ones): Baicalein, Noscapine, Mebendazole, Albendazole, Celcoxib, Shark Cartilage, Thalidomide, Curcumin

Here is a nice reference for Albendazole:  Albendazole: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation in OVCAR-3 tumor-bearing nude mice.http://www.ncbi.nlm.nih.gov/pubmed/16551879. The only drawback related to Abendazole is the liver toxicity. On the other hand I know a cancer patient who is taking it for a long time with no major issues.

Mebendazole is on the other hand one of my favorites.

Thalidomide is another VEGF inhibitor I specifically like. I intend to write a post on Thalidomide only, but for now here are few words about it: Thalidomide has been shown to be potent in inhibiting tumor necrosis factor (TNF)-α, IL-1, IL-12, and VEGF in addition to IL-6, and can stimulate T cells via its interaction with cereblon 10,11. It has been also demonstrated that thalidomide is capable of decreasing IL-6 levels, lowering C-reactive protein, and, thereby, inducing remission in MCD. Ref:  Thalidomide for tocilizumab-resistant ascites with TAFRO syndrome http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498865/

Regarding the inhibition of M2, I wrote sometime ago an article on my page http://www.cancertreatmentsresearch.com/?p=265

Note:  M2 responses are associated with growth factor production (e.g., VEGF or EGF) http://journal.frontiersin.org/article/10.3389/fimmu.2015.00212/full#F1 so inhibiting growth factor production would have inhibiting impact on M2 response.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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Fred
Member
Fred

This is helpful Daniel. Always disturbing to see a promising drug, mebendazole discontinued (no reason given) and unavailable in the U.S. The following suggests Albendazole/mebendazole should be explored:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096024/
Albendazole or other benzimidazole: There is evidence that the different benzimidazoles vary in their molecular targets and that combining them may improve efficacy and reduce the risks of acquired resistance. While this approach has not been explored in a cancer setting, there is pre-clinical and clinical evidence that the combination of MBZ and albendazole is a more effective treatment in certain hard to treat parasitic conditions [8, 9]. There is also some in vitro and in vivo evidence where albendazole exerts an anti-angiogenic action by down-regulating vascular endothelial growth factor (VEGF), an effect mediated through inhibition of tumoural hypoxia inducible factor (HIF-1α) [10]. As HIF-1α is implicated in multi-drug resistance in cancer, the combination of MBZ and albendazole warrants further investigation in drug-resistant tumours.

Fred
Member
Fred

I was able to order Thailand Mebendazole in 100mg (Vermox) and 500mg (Benda) packages. The downside is it takes 2 or 3 weeks. I don’t think the shipment will run into import problems but I’ll let you know.

Fred
Member
Fred

Daniel, both Vermox and Benda came in from Thailand with no delays. We started with Vermox 100 and have moved to Benda 500 (+cimetidine), 1x/day. Is your wife taking it daily or # times per week?

Fred
Member
Fred

“… Carbamazepine and phenytoin lower serum levels of mebendazole. Cimetidine does not appreciably raise serum mebendazole (in contrast to the similar drug albendazole), consistent with its poor systemic absorption. …”

http://research.omicsgroup.org/index.php/Mebendazole

madama
Member

hi all,

do you think it can be problematic if we take thalidomide and albendazole together?

madama
Member

hi daniel

i m going thru contact in countries where this is available at cheaper price.

i could help people to get it if needed

thanks

Hanh
Guest
Hanh

Hello, I would like to get this med. for my husband. Did you be able to find a source. Thank you.
Hanh

alternmed
Guest
alternmed

hi hanh

this is madama

please contact me thru pm at cancercompass ,my nickname is alternmed there.

i m trying to post using my nickname madama,but the website is blocking me

thanks

Hanh
Guest
Hanh

Thank you, my husband situation was taking a turn for the worse after 1 week on Stivarga. His bilirubin shot up, his tumor marker shot up.
His oncologist pushing for hospice. I am not confident in self treatment not when his condition is this critical. So we went to an integrative clinic
Hopefully this doctor can turn thing around. I would ask for your help once his stiuation is stable.
Thanks,

Masato Hada
Guest

To Mr Daniel
The effective treatment of ascites is to use VEGF inhibitors, I think the combination of thalidomide, celecoxib and low dose cytotoxic drug is essential.
In order to eradicate H.pylori, proton pump inhibitor and antibiotics must be combined.
It is impossible to eradicate with proton pump inhibitor or antibiotics alone.
Masato Hada

Reference ReseachGate
Report of two cases with pleural effusion and ascites that responded dramatically to the combination of thalidomide, celecoxib, irinotecan, and CDDP infused in thoracic and abdominal cavities.

Masato Hada
Guest

To Mr Daniel
The eradication of H.pylori is nothing to do with the treatment of ascites at all. This is metaphor.
My expression and English were bad, sorry. I would like to say that PPI only or antibiotics alone could not eradicate H.pylori. Like the eradication of H.pylori , to prevent the accumulation of ascites, cytotoxic dug only or targeted drug alone is not effective. I would like to say that the combination of proper drugs is very important.
Masato Hada

Emad
Member
Emad

There is something strange these days

my mother is improving very fast , but also it looks like ascites is increasing !!!

I don’t know how something like this could happen , good and bad at the same time

I contacted prof Vogl , he said that we should treat the cancer to eliminate ascites

and he didn’t prescribe any drugs to help reduce it

——-

I don’t have thalidomide , I don’t know is it ok to let the ascites increase without using diuretics ? or its better to treat it before it increases even more ?

Ergin
Member
Ergin

Treating ascites with diuretics is not impossible.
But less chance.If you ll use , please look
for blood pressure and blood counts.
Dapagliflozin is also diuretic.

Ergin
Member
Ergin

And most important,you have to know CRP!.
Inflamation!?
And albumin,iron,thyroid levels for embolism.

Ergin
Member
Ergin

Avastin works perfect for some patients,i know it is very expensive.
We talked with Dr Hada about comparison thalidomide and avastin a year ago.
He said thalidomide has less side effects.
When i look gene sequencing results of lots of patients,i saw thalidomide is not effective to all.
Thats why i did not use it.But now i am thinking different.It is a good drug should be think to try.

Pouya
Member

Hi Emad, who you have to ultimately take advice from whether to tap the fluid now or not, Vogl or your local dr?
how is the urine output currently?

Emad
Member
Emad

prof Vogl usually is not interested in something not necessary , but I did ask many doctors locally here , and they said :

if ascites become annoying .. its better to start with diuretics (Lasix + aldactone) , if nothing goes well then tap it out and give albumin

her urine output looks like normal , I’m not sure

Pouya
Member

and did Vogl mention Prednisolone to you?

Emad
Member
Emad

Yes he did prescribe Prednisolone , but does it affect ascites ?

Pouya
Member

https://www.ncbi.nlm.nih.gov/pubmed/1986555
is your mom already taking it?

Pouya
Member

another thing that I found that might come in handy is this:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081395/

anyone can shed some light on Lonidamine? it’s new to me.

Ergin
Member
Ergin

Dear Pouya,
Lonidamine is a substance works like 3BP.
We know it from phlorizin patent.
Kind Regadrs
Ergin

Emad
Member
Emad

Recently my mother has Ascites which was increasing day after day , until she felt hard to breath

but just after 2 days of diuretics , the fluid looks like decreased a lot !!!

first : is this possible to happen just in less than 2 days ?

second : how to maintain this response ?

Pouya
Member

Hi D and other cancer fighters, today I’m here to seek advice for a dear father of a friend who is a late stage liver patient currently battling alcoholic cirrhosis of the liver as well as some tumors present in the liver.( I’m not very clear about the exact diagnosis and the tumor load and I’m only sharing what I have been told).
apparently liver transplant is not an option even though they are getting second opinion on the matter. from what I understood the challenges include blockage of hepatic and portal vein (pvt?) which has been treated with enoxaparin, (unsuccessful probably)
patient has gradually lost a lot of weight and mobility since 3 weeks ago and can only travel to the bathroom. (due to Hepatic Encephalopathy?). urine output is good and the patient is getting the standard regimen of diuretics. I’m not informed whether the patient is constipated or not.
the last Hematology and ascitic fluid markers which is dated a week ago are:
20 cc of fluid:
before centrifuge: Color: Bloody appearance: Turbid
After Centrifuge: color: yellow appearance: clear
LDH: 86 – Sugar: 115 – Protein: 1.2 g/dl- Albumin 0.8 g/dl
R.B.C 160000 cell/mm3 – WBC 300 PMN 30 %
Triglyceride: 44 mg/dl- cholestrol: 28
______________________________________________
Hematology:

W.B.C: 9.72
R.B.C: 4.31
Hemoglobin 12.8
HCT 34.7
MCV 80.5
MCH 29.7
MCHC 36.9
PLT 311
RDW 22.7%
PDW 13.2
MPV 10.4
PLCR 29.7 %
NEUT 83.7 %
NEUT value 8.13
Lymph 10.9 %
Lymph Value 1.06
Mono 5
Mono Value 0.49
Eosin 0.3 %
______________
this is what I got so far. patient is not under chemotherapy currently and the liver mass has been tread with embolization a year or so ago.
hope this helps you form an opinion. please let me know what you think/ would do and what are the best possible course of action to take in this tough situation. and if there are any other pieces of info which may help here. let me know so I can ask the family members and share here. thanks in advance.

Shanti
Member
Shanti

Hi Pouya, I am sorry to hear about your friend’s father, it sounds like a difficult medical situation. It is hard to tell from what you have posted if this individual is in his condition primarily because of the cirrhosis or the cancer or both? It would also be helpful to see some liver markers or tumor markers. In my experience, a damaged liver can be very responsive to supplements such as milk thistle, SAMe, and NAC, but once someone reaches end-stage cirrhosis there is not so much response because the liver is now mostly scar tissue. Also, supplement choice would depend on the degree of cancer involvement in the liver. Life Extension has a nice protocol on Cirrhosis, but again, I’m not clear on what the situation really is: http://www.lifeextension.com/Protocols/Gastrointestinal/Cirrhosis/Page-01.
My best to you, -Shanti

Pouya
Member

thanks for your response Shanti. you are correct, in all honestly I’m not exactly clear whether the condition is mostly due to cancer itself or cirrhosis, based on the treatments they have got, my guess is that it’s mostly cirrhosis.
I think at this point a serious professional intervention is what they should be looking for since it’s very hard to self treat at this stage, may times it’s hard to tell whether the symptoms one sees is due to cancer, cirrhosis or side effects of therapy.
I think my real question here is that is anyone aware of a clinic that would accept a patient in such critical condition or has successfully treated one?

Pouya
Member

update on tumor markers: AFP: 46.85
CA 125: 1403
CA 19-9: 100.6
CEA: 6.0

Alex
Member

And the previous values are?

Pouya
Member

this is all I got Alex. I guess we should base our assumptions on the physical condition of the patient which is not good.
they have been told that liver transplantation is only possible if they can treat portal vein thrombosis successfully. patient is being treated with Enoxaparin currently.
I’m pretty sure I have come across accounts of liver transplant with PVT present. dunno why this patient should wait in this critical condition.

Pouya
Member

I don’t know why my comments await moderation. do I have to reach a certain post count?