Treatment of FIP

If you came here hoping for information that can help your Fippy friend we wish you all the best.  Be kind to yourself and don't forget to fit your own oxygen mask first!

Update 2020:  CURE FOR FIP FOUND both wet and dry 80% effective START GS441524 QUICKLY FOR BEST CHANCE

Ordering and more information from Dr Adie here. https://onecatlife.blogspot.com/2020/01/gc-441524-and-mutian-cure-fip-happy-new.html Join the facebook groups. Good luck!

GS 441 524 https://www.curefip.com/pages/success-stories

MUTIAN https://www.mutianstore.com/blogs/mutian-warriors

========historic info=========
  This information is now for background interest. Not a substitute for veterinary advice. All drug treatments were considered experimental and ineffectual in most cases although it may be the timing of the treatment ( too little too late) that is the problem. In Dr Addie's experience 80% of cases referred to her are NOT FIP. Here is her video showing steps to diagnosing dry FIP http://www.youtube.com/watch?v=_JLdLQKpoyA
and a case study showing steps to diagnosis of wet FIP incl. Rivalta test and details of treatment of the case http://www.almonature.ch/de_ch/index.cfm/vet-forum/verschiedene-fachthemen/feline-infectious-peritonitis-fip-case-study-2/

FIP DFA: FIP direct fluorescent antibody test from Colorado State University CVMBS provides   quick cheap testing on effusion, lymph node aspirate, and tissue samples. A positive FIP DFA staining will provide a definitive FIP diagnosis; however, a negative FIP DFA result does not exclude the possibility of FIP.  $20 per sample. Submit effusions by one of two options:

• Make a smear of the effusion fluid at the clinic, which will then be stained by FIP DFA here at the lab
• Submit the effusion in a purple-topped tube (EDTA).

Dr Pedersen's comments about diagnostic tests Also he says there is no treatment, it is 100% fatal though cats with dry FIP may live seven years with their disease. UPDATE: his FIP synopsis relates cases of spontaneous resolution and healed FIP although once again stating FIP cats universally die of their disease (this seems a bit of a non sequitur to me)

The dutch researchers at University of Ghent say "When clinical symptoms arise, a FIP infection will lead to death in 95% of the cases." so you have a 5% possibility of a cat surviving the illness ( they do not say if this is with specific treatment - only that "Currently, there is no efficient treatment for FIPV" ) The quoted 5% one year survival rate on PI may therefor be no different and this is why Pi and interferon are not approved as a therapy a manufacturer can advertise for FIP.  Reading through the case histories though one can clearly see though that in some cases heroic interventions provide a respite with good quality of life for several months that was not happening spontaneously.

Mishka was diagnosed wet fip lung/abdo in aug. 2012 but since she had already undergone the trauma of emergency drainage of her chest and four days fighting her way back to the land of the living while I googled desperately for advice, we decided to 'go for gold' since she was so young but still strong and fully grown. She survived over 5 months eating well, doing cat things and mostly very happy so I felt i had to add more treatment links to this blog which was originally I thought mostly going to be dealing with grief and other musings of a general nature on illness. I prefer to use the term healed now, not cured. It's experimental therapy and we have made a lot of mistakes I hope you can profit by. 
Treatment doesn't always bring you or kitty any peace in the short term - the cat has to go through a fair bit of stuff he won't like or understand. Think 'kid with cancer', think financial stress. If you have cast iron cheerfulness, great faith, deep pockets or a strong belief in holistic medicine you can try a number of therapies.

Perhaps the easiest thing for wet FIP to make kitty comfortable and buy you time to think, to say goodbye if nothing else - is drainage of fluid. Sometimes against the odds this supportive therapy helps get them enough time to get over the line (see Tam and Blade) You MUST find a good vet. Mishka was drained every week and given a supplemental dose of vit c and electrolytes subcutaneously at the same time ( cost $88+ half a day of being 'stoned'). We tried waiting two weeks initially but that turned out to risk getting uncomfortable and causing intestinal obstruction. However I couldn't always get the timing for the patient. In an ideal cat-centric world she would have been the priority not fit in with vets days off/weekends/christmas/golfing. She would not have had to travel or wait in a surgery full of barking dogs until she was hysterical with fear. ( we didn't go back to that vet ) 12 days would have been better. She was perking up mentally and her energy was improving up till mid january on the interferon, colostrum and PI added in Dec, but still losing ground gradually - too many goodies drained out with the nasties.

If you join FIP facebook group or read the survivor and other case studies on my blog some other downsides are mentioned, as well as cases of mis-diagnosis as well as cures / managed chronic disease with good quality of life.

2018 DEC UPDATE: TIME IS OF THE ESSENCE - it appears if treatment is started within a certain time frame you may be able to cure your cat from wet and the dry form with an antiviral called 3C-like protease inhibitor GC376 mostly for wet or with polyprenyl immunolstimulant (PI) mostly for the dry form 
PI has the longer track record and is more affordable. See the case histories under 'survivors' and other information below which is dated 2012 and the updated website order here http://vetimmune.com/pi-product-information/  

GC376 is a looong shot I haven't added up the possible cost but probably ASTRONOMICAL THOUGH i think its cheaper than reported BY THIS ARTICLE The research is unpacked with commentary here - http://fipcaregroup.com/pages/GC376-protease-inhibitor.html the compound is available for $17 per mg - the price falls with bulk purchase here https://aobious.com/aobious/products/9734-gc376.html

CONTACT UC Davis
http://debraroberts.net/2017/10/lunas-drug-trial-update-10-weeks-out-and-labs-are-perfect/

you might elect to just DIY as per the trial below
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814111/

Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

Table 1

Clinical and laboratory findings in cats challenged with FIPV prior to antiviral treatment.

	Clinical and laboratory findings prior to treatment
Cat	Fever	Weight loss	Jaundice (mucous membrane or plasma)	Ascites	Lymphopenia (<676/μl)	Treatment duration (dpi)*	Outcome
P07	+	+	+	Not apparent	+	20 days (15–34)	Recovered
P10	+	+	+	Not apparent	+	20 days (15–34)	Recovered
P02	+	+	+	Mild	+	15 days (20–34)	Recovered
P03	+	+	+	Mild	+	16 days (19–34)	Recovered
P17	+	+	+	Profound	+	14 days (21–34)	Recovered
P24	+	+	+	Profound	+	14 days (21–34)	Recovered
P15	+	+	+	Profound	+	4 days (18–21)	Euthanized
P16	+	+	+	Profound	+	7 days (18–24)	Euthanized

* dpi, days post infection

-----------------------------------------------------------------------------------------------

J Feline Med Surg. 2018 Apr;20(4):378-392. doi: 10.1177/1098612X17729626. Epub 2017 Sep 13.

Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis.

Pedersen NC1, Kim Y2, Liu H1, Galasiti Kankanamalage AC3, Eckstrand C4, Groutas WC3, Bannasch M1, Meadows JM5, Chang KO2.

Author information

Abstract

Objectives The safety and efficacy of the 3C-like protease inhibitor GC376 was tested on a cohort of client-owned cats with various forms of feline infectious peritonitis (FIP). Methods Twenty cats from 3.3-82 months of age (mean 10.4 months) with various forms of FIP were accepted into a field trial. Fourteen cats presented with wet or dry-to-wet FIP and six cats presented with dry FIP. GC376 was administered subcutaneously every 12 h at a dose of 15 mg/kg. Cats with neurologic signs were excluded from the study. Results Nineteen of 20 cats treated with GC376 regained outward health within 2 weeks of initial treatment. However, disease signs recurred 1-7 weeks after primary treatment and relapses and new cases were ultimately treated for a minimum of 12 weeks. Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1-7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission. Five kittens aged 3.3-4.4 months with wet FIP were treated for 12 weeks and have been in disease remission after stopping treatment and at the time of writing for 5-14 months (mean 11.2 months). A sixth kitten was in remission for 10 weeks after 12 weeks of treatment, relapsed and is responding to a second round of GC376. The seventh was a 6.8-year-old cat with only mesenteric lymph node involvement that went into remission after three relapses that required progressively longer repeat treatments over a 10 month period. Side effects of treatment included transient stinging upon injection and occasional foci of subcutaneous fibrosis and hair loss. There was retarded development and abnormal eruption of permanent teeth in cats treated before 16-18 weeks of age. Conclusions and relevance GC376 showed promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.

PMID:

 

28901812

 

PMCID:

 

PMC5871025

 

DOI:

 

10.1177/1098612X17729626

Free PMC Article

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The following links are a historical record of our fight against FIP with Mishka - information is not current please check

Polyprenyl Immunostimulant (PI) 

an immune stimulant by Sass & Sass, Inc. USD$199 for a six pack of 10ml vials ( 2mg/ml ) + postage and handling fees. The vet may mark this up - if he/she orders it specially for your pet then let them know you know the direct price. It is considered unethical to charge a mark up for off label experimental usage.

Treatment with Polyprenyl Immunostimulant (PI) for FIP is an 'off label' use. As such the manufacturers are unable to advise dosages which must be prescribed by a vet - you might like to ask for name of a vet they have previously worked with in your area or see the list on the blog.  The FIP dose is weight based 3mg/kg (1.5mls/kg) and given orally usually mixed in a little food second daily initially though treatment should be individualised. Can be taken daily; two wet FIP cats are currently doing well on 0.5mls twice daily ( not a weight based dose ). Dose tapers very cautiously ( they might stay on the dose for years ) once the cat responds. 

The product may be injected if diluted with saline (injected dose is different and twice daily). The studies in feline infectious peritonitis (FIP) are directed by Dr. Alfred Legendre (UTK). Details of use in FIP with FAQ's http://www.vet.utk.edu/research/fip/fip.php 

Please see my survivors page for individual doses given to FIP cats who are doing well. Oliver McKinnon has been taking 5mls daily for 3 years and is only just starting to taper his dose. There is one single case of a wet FIP cat surviving on PI that I am aware of - the kitten is called "Miracle".
Mishka we felt had a good response to PI; I feel it contributed to her excellent quality of life up until her death but it was administered very late and didn't make any headway into the effusion which was killing her.... so hard to be certain. Other cats who have wet FIP have had no response.
PI is only licensed for reduction in signs of feline rhinotracheitis caused by Herpes Virus ( the 0.5mg/kg dosage on the bottles relates to this, not FIP ). Recommended for use in cats at eight weeks of age or older. "In our safety studies, we had no problem even with kittens as young as 1 week -- very safe. The dose should stay at 0.5 mg/kg twice daily for rhinotracheitis. In case of severe conjunctivitis, she may mix it 1:1 with saline and use as eye drops as well. Dr. Legendre tried that for safety -- it was safe." Tanya Kuritz just told me it could be used that way because we got some PI sent out to a tiny kitten with herpes. No dose given just the dilution ratio - I have no idea if it is any extra help for uveitis in FIP that way.
Apparently some cats think it tastes nasty so can have extreme trouble dosing. I made a video of the method we settled on - syringing it was too stressful and too much on the floor. May be used with steroids but this is usually not reccomended since steroids are immuno suppressive in the medium to long haul and slow down healing.

PI is now distributed by vetimmune.com If you need to place an order or have a question, please call VetImmune in the USA 209-600-7070 or use PM on this page, or fax 865-940-0042;  or    Twitter @vetimmune There still appears to be a dreadful slackness about their idea of timely response to internationals. I would strongly suggest you just do the black market thing at your own risk as I did for Mishka if you want a fighting chance  as I keep hearing of people who have gone to the expense and delay of obtaining permits only to have the insult of the PI arriving after their pet is dead. Essentially I placed an open request for someone to send us a packet by regular international expedited post without any special customs clearance. It was marked as a sample as it was indeed a left over from the trials sent by someone whose cat didn't make it :( Customs opened the package, inspected and passed it straight on to me without extra charge. The lunacy is that this was quicker and cheaper by several hundred dollars than when we used official channels ( yes same customs officers which is ridiculous - see the sorry saga below. ) . At any rate it was here in two weeks which was fast enough for us to try it with Mishka - she seemed to perk up and have  a really good last 6 weeks with us. We even thought we might win. It bought us enough time to get the permits and start importing properly for ourselves and for other cats in any case although none responded as well as Mishy. Steph Lambourne has taken over brining it in for Australia - she had several spare packets in reserve and may be able to dispatch from here.

Australia  requires biological material import permit from AQIS  applicable fees are several hundred dollars (it is a category 5 item). They can fast track approval if you tell them it is a medical emergency otherwise 2 weeks. They may still charge another AUD$65 when it lands to read their own forms! Shipping is some sort of spot price with Fedex + Sass&sass charged additional $25 handling per order to fill in forms. (USD$145 by Fedex to australia for latest 2 packs in June. i don't know how things are going to be sent by the new distributor vetimmune.com. (Sassandsass wouldn't use USPS which in my previous experience costs about $30 and did not attract the extra customs; customs opened the boxes, sticky beaked, closed it and sent it on) Ordering more than 4 packs at once may also put the shipment over the GST threshold.

I found two websites particularly useful for understanding the therapy of FIP in terms of the disease spectrum of immune failures ( allergy/intolerance, auto immune, chronic viral illness, cancer ) Bud's therapeutic Guidelines and Dr Heinrich Kremer's book on AIDS and Cancer. The complete work is online  - see links in this post.

Bud’s Medications and Supplements - must read

The Bible of supplements for viral illness of cats is this website by Joel Kehler who was adopted by an FIV positive cat called Bud - http://www.fivtherapy.com/bdmeds.htm read and bookmark it! Of course Bud had FIV which is a retrovirus not a coronavirus but this website is incredibly practical, well researched and well written (by a retired english teacher) and Joel is very kind - will answer questions promptly. I was so pleased to find info that was not coming from a vendor.
Using his guidelines to therapy I selected a number of supplements including ketotifen, lactoferrin, NAC, coQ10 and glutamine. Also listed is the thymus supplement I gave her, Proboost (thymic protein A).

Feline Omega Interferon (FOI)

Given by subcutaneous injection every second day initially tapering according to response - may be ceased. Usually given with steroids for reducing inflammation. Must be refrigerated, 5x2ml 10MU vials for reconstitution. AUD $1000+ per pack.

http://www.dr-addie.com/treatment.htm Dr Diane Addie's UK website - "Interferon Omega does seem to effect a cure in around a third of cats with FIP."  Wet FIP healed - Australian case study Dusty.  You should read this alongside the detailed case history of a wet FIP cat who also died around the 7 month mark ( Abbey )
Tomten who haddry FIP diagnosed about the same time as Mishka, was doing extremely well on FOI injected every ten days. Recently he has deteriorated with much expensive surgery and vets questioning FIP/notFIP. He turns out to be PCR negative for coronavirus so not FIP.
In France Tam diagnosed jan 2013 wet FIP lung had antibiotics + 4 and a bit shots of FOI amongst other things and is now considered in remission. Please read her case carefully - this is not a cut and dried case of wet FIP; Dr Addie who is consulting on the case does not think it is FIP actually, and arranged for a trial of a new mitochondrial antioxidant from Russia called SkQ1. Tam was still well early 2014 a year later

Isheda Protocol

This product was first used in treatment of FIP by Japanese vet and scientist Takuo Ishida. He presented his data at SIFFS and his abstract can be read on the SIFFS website. This is his protocol:
IFN omega was initially given subcutaneously at 1 MU/kg every other day, and then once every week for variable period if remission was seen.

Glucocorticoid: (dexamethasone 1 mg/kg intrathoracic or intraperitoneal injection once only) or prednisolone. Oral prednisolone was initially given at 2 mg/kg once daily, and the dosage was gradually tapered to 0.5 mg/kg every other day after remission.
In Dr Ishida's study, 4 cats of 12 completely recovered and two survived 4 and 5 months. Those cats which recovered completely all had the effusive form of FIP and were relatively older cats."

Obtaining FOI

In Australia ask your vet to contact Mark Kelman direct at Virbac (the manufacturer) to discuss your case and obtain Feline Omega Interferon (FOI) via Provet (the supplier). It is not licensed as therapy for FIP in Australia (unlike in the UK) so I found out about it circuitously - damn the delay.

How to Order FOI in the USA 

It will be shipped from AbbeyVet UK to your vet. Your vet has to contact Katy Janik orders@abbeyvet-export.co.uk - she will send all the information required. This will be faster than going through the website. Your vet should also have a prescription ready to submit.
Katy Janik
Export Administrator
Abbeyvet Export LLP
Sherburn Enterprise Park
Aviation Way
Sherburn-in-Elmet
Nr. LEEDS
North Yorkshire
LS25 6NB
ENGLAND

Office Tel: +44 1977 685777
Office Fax: +44 1977 685111
E-Mail: orders@abbeyvet-export.co.uk
Web: http://www.abbeyvet-export.co.uk

Human Interferon (Roferon, Intron-A)

Protocols for dry and wet FIP and instructions for dilution http://www.dr-addie.com/treatment.htm#Interferon (also more info at Bud's FIV therapy website)
Easy to get in USA, UK and probably also Australia, very very cheap and oral dose but eventually cats can get antibodies to it - if the dose is high this is quick, at very low FIP dose this may be not a problem. There are a few cats apparently doing well on this with steroids. The longest that I know of is Blade who belongs to Joni Swanson - you will have to join fip fighters facebook page to talk to Joni. Blade has been treated with interferon with weekly ( now monthly ) abdominal drainages for 2 years!

Moducare (and FIP-to-Health Homeopathy group)

http://pets.groups.yahoo.com/group/FIP-to-HEALTH/ practical help even if you do not want to use homeopathy. Their recommended immune supplement is a plant extract from pines called 'moducare' ASPEN brand : http://www.nutri-health.co.uk/detox_and_immunity/moducare__90_capsules/24271_p.html  (Aspen brand is more pure, very small capsule that cat can eat whole in food even) or a the not so pure version by Thorne "Moducare" can be bought from iherb.com or in australia/nz for around $50 I can also order it for you from wholesale supplier in NZ (roughly 6 days transit) Bigger capsule - the filler is the inevitable magnesium stearate, I sprinkled it on Mishka's food twice a day, half capsule. The loading dose for two weeks is double that - try to give away from main meals and not with calcium as that binds it.

caveat: the list owner Irene is not licensed to diagnose, very judgemental and can be extremely rude to people both on and off list if they disagree with her. Also she deletes any posts that have any information other than what she approves of so you won't get any other possibly helpful information.
Irene de Villier's makes amazing claims for FIP cure although in the 11 months I have been a member no one is celebrating such a victory on list. Sharon Hamel is very quick to respond and helpful. She says Dr Addie's website has a lot of bad information on it. Homeopathy is not contraindicated if you are using any other treatment although the group managers do not reccomend either antibiotic, interferon or steroid use. Steroids in particular will cause involution of the thymus gland.  
Note for greenhorns - homeopathic remedies for cats should not be bought as drops which have alcohol preservative. Cats can't detox it and hate the taste. I bought those as that was all that i could get quickly and tried the method of heating off the alcohol but that didn't work so applied to skin but Mishka still hated the smell. It wasn't helping anyway so I stopped using it after a fortnight and went for the interferon.

I did try the homeopathic remedy from their quick start guide to little avail, and contacted an australian vetinary homeopath who unfortunately responded by contradicting most of what Irene reccomended with regard to feeding ( I stuck with Irenes guidelines) and furthermore saying she had stronger things to offer than homeopathy - alarm bells. But lets not throw the baby out with the bathwater. Taking all their advice and checking it thoroughly I still can reccomend this group's quick start post to new members as somewhere to start with practical, sensible treatments that would be supportive of regaining health from any illness, in particular the gut health guides. FIP starts in the gut - so It made sense to me to look to start healing it there. It was one of the first and only encouraging reading on FIP I found. She gave me hope, a place to start, ideas that have obviously benefited Mishka who wouldn't have made it 5 days let alone 5 months without it.

The groups files are in disarray, many of the first 5 folders are empty but the information is contained in the later folders - be patient, click through them all quickly and just print out anything you find useful to read offline rather than try to find it again.  Also if you are using Alpha lipoic acid ALA be aware there are two forms - pure and inactive - the dose will be less for pure formulas. ALA depletes biotin so it must be given together - this was in the files but not in the group welcome letter. Kitty's fur started falling out alarmingly at one stage; whether from the ALA or the wretched riprap bandage i don't know. I think the toxic dose is too close to the therapeutic in cats so I do not use it  - i used NAC ( N acetyl cysteine ) instead.

Experimental Anti Virals

http://debraroberts.net/2017/10/lunas-drug-trial-update-10-weeks-out-and-labs-are-perfect/

Synergistic antiviral effect of Galanthus nivalis agglutinin and nelfinavir against feline coronavirus http://www.ncbi.nlm.nih.gov/pubmed/20603153 In 2010 taiwanese researchers found the poison from the snowdrop plant mixed with Viracept worked in the petri dish against FIP. 

In searching for agents that may prove clinically effective against FCoV infection, 16 compounds were screened for their antiviral activity against a local FCoV strain in Felis catus whole fetus-4 cells. The results showed that Galanthus nivalis agglutinin (GNA) and nelfinavir effectively inhibited FCoV replication. When the amount of virus preinoculated into the test cells was increased to mimic the high viral load present in the target cells of FIP cats, GNA and nelfinavir by themselves lost their inhibitory effect. However, when the two agents were added together to FCoV-infected cells, a synergistic antiviral effect defined by complete blockage of viral replication was observed. These results suggest that the combined use of GNA and nelfinavir has therapeutic potential in the prophylaxis and treatment of cats with early-diagnosed FIP.

( GNA galanthus nivalis agglutanin - buy it here if you are a researcher http://www.medicago.se/galanthus-nivalis-lectin-gna ) An american lady tried to obtain and use these in vivo for her FIP cat Lenny. Read about her brave attempt to cure her cat stymied by access to GNA, a readily available plant extract here. He responded to the Viracept alone knowing it would only be for a short time unless she got the GNA.

I have since learned that it is easy to make your own preparations from the snowdrop plant for experimental therapy; This blog relates to a human with neurological disease but it may give you somewhere to start http://lymeuk.blogspot.com/2013/07/snowdrops.html

Euthanasia

For some it is the first treatment of choice; others don't want to think about it while in the healing mindset. I think it is best to at least make inquiries about home euthanasia rather than be caught with an emergency after hours as we were, which is particularly possible if your cat has wet FIP as it often compromises breathing very quickly. People have had some really bad experiences with cats trying to claw their way out of the carrier at the vets - at home is calmer for them. You may need to be aware cats eyes do not close.
Mishka's vet did not offer to come over if we needed to euthanase and I never thought to ask. An assisted passing can be a blessing and some vets take their duty of care above and beyond. I could only wish my own end may be as surrounded in love and peace as that of some FIP cats I know.

Dr Yasson’s Guidelines for GastroIntestinal Troubles

Holistic vet Dr Yasson's excellent guide for managing the intestinal distress if FIP and natural diet advice. http://www.holvet.net/slippery_soup.html

Digestive Enzymes

useful for helping a sick cats get the most from her diet and denaturing viral protein coat. May contribute to decreasing inflammation as well. We gave Mishka a plant based enzyme supplement with her meals as per Irene de Villier's reccomendations. Can't remember the brand - it was a human supplement plant based, no fillers, from health food shop which I opened and mixed a small amount into each meal for the duration of her illness.  I did some research and we tried Serrapeptase as well since it has been used in vasculitis and against viual illness - but i think even only one small cat sized dose made her effusion worse. I don't know for sure. The PI arrived the same day.
There are no pet specific brands of enzymes in australia except for one i found only recently http://biohawk.com.au/animalhealth.html - a proprietary formulation of extracts/ground ginger root - well known as a digestive which cleaves proteins. This stuff has been researched for the human coronaviruses. (SARS MERS) Dr Cliff is right on it - he even sent me the exact protein codes for the feline corona spike protein and highlighted where the enzyme makes the cuts! and it should also prevent transmission by denaturing the virus in the gut - put usual dose into the food and bigger dose with small amount of food between meals. I think that it is useful anyway if one has to feed crap commercial food to the cat who is addicted to a certain brand. Talking to him more by phone tomorrow to clarify. The WHO in HK trialed the product against SARS i think, but its not common knowledge so i only just found it while footling about looking for gluten free flour. He also can't advertise it for use in cancer etc. but he will be doing clinical trials in glioblastoma and multiple myeloma asap because people have used it as a last ditch effort (these cancers do not respond well to standard treatment).