Phase 2 DFMO preventative trials

(Alexey) #21

Another recent article about DFMO:

@sam - seems your doctor is one of the authors…

(Alexey) #22

Potential future enhancement of the DFMO therapy:

Separately, each drug impeded neuroblastoma in laboratory tests, but when administered together, the two drugs acted synergistically and were more than twice as effective in blocking the cancer’s growth.

“Instead of one plus one equals two, it equals four,” Bachmann said, who is also a professor of pediatrics and associate chair for research in the College of Human Medicine’s Department of Pediatrics and Human Development. “That’s why the synergistic effect is so important. We can use the two drugs in lower doses, thus achieving the same result while minimizing side effects.”

(Sam Saffron) #23

Yeah that trial is very different to the DFMO preventative trial. It is given in a much higher dosage in combination with chemotherapy. (for relapse)

(Kyle Matthews) #24

I am unable to pull up that link. Do you have the author or full text or another link? I’ll check again later.

(Alexey) #25

Try to search “Metronomics — an alternative P4 medicine” in Google and the first link will be this one. This is a publication in Nature Reviews Clinical Oncology (author is Lisa Hutchinson).

(Kyle Matthews) #26

Found it, thanks! And actually that first link works now. :slight_smile:

(Donna Ludwinski) #27

Hi Sam – Myriam is an amazing Mom. I met her in Toronto at ANR in 2012. Muli never got MSK vaccine – they went to Hershey to get Ken Lucas dendritic cell vaccine.

(Mark Shirran) #28

Here are the latest figures from Dr Sholler’s DFMO trial presented in an abstract for SIOP 2016.
There are a handful more patients included since the last abstract published earlier this year for ANR 2016, which was previously copy+pasted in this thread.


G. Saulnier-Sholler1,2, W. Ferguson3, G. Bergendahl1, K. Neville4, D. Eslin5, W. Roberts6, R. Wada7, J. Oesterheld8, D. Mitchell1, J. Foley1, V. Brown9, N. Parikh10, F. Eshun11, P. Zage12, J. Rawwas13, S. Sencer13, D. Pankiewicz1, M. Quinn1, M. Rich1, J. Kraveka14

High Risk Neuroblastoma (HRNB) remains a challenge, accounting for 15% of all paediatric cancer deaths. While most attain remission, the natural history of HRNB is well documented with approximately half of patients relapsing within 5 years after completion of immunotherapy. This study evaluated the effectiveness of the ODC inhibitor difluoromethylornithine (DFMO) as a maintenance therapy to prevent relapse in HRNB patients after the completion of standard therapy.

This study was a single agent, multicenter study, enrolling from June 2012 to February 2016. Patients received 27 four-week cycles of oral DFMO at a dose of 750 ± 250 mg/m2 twice daily. Event free survival (EFS) and overall survival (OS) were determined on an intention-to-treat basis.

A total of 101 patients received DFMO, 98 were eligible for the intention to treat (ITT) analysis. For all ITT patients, EFS was 89% (± 4%) and OS 98% (±2%) at 2 years. For the subgroup of patients (n=79) who had been previously enrolled on ANBL0032 prior to starting this study, the 2 year EFS was 92% (± 4%) and OS 98% (±2%). DFMO was well tolerated, with grade 2-3 transaminitis being the most common toxicity reported in <10 % of patients.

DFMO at 750 ± 250 mg /m2 BID following completion of standard therapy for HRNB is safe and associated with improved EFS and OS in children with HRNB. DFMO is now currently undergoing further evaluation in a prospective confirmatory study for additional safety and pharmacokinetic analysis.

Original link can be found here (on page 351):

(Tomica Tomek) #29

I think it’s very good the result. Does anyone know whether DFMO applied in the territory of the EU. I’m seriously considering accession to this type of treatment
Thank you all for your replies

(Alexey) #30

Hi Tomica, As I know this trial is available only in US

(Tomica Tomek) #31

Alex. Thank you for your answer.
About Siopen., does anyone knows future planing after immunoterapy as front line medicine while
Patients in complete remision?

(Sam Saffron) #32

Neither SIOPEN or COG have any plans to introduce DFMO post frontline, both bodies are being very skeptical about the results.

The current plan for SIOPEN is to introduce an anti idotype vaccine post frontline, but dr. Lode has no timeline for availability of his vaccine trial.

(Kyle Matthews) #33

I continue to be confused at their “skepticism” about results (are they genuinely suggesting the entire NMTRC research consortium is lying to or intentionally misleading the community?! that is insane). In fact, it is quite possibly a harmful mistruth to spread when the results have been so encouraging.

(Sam Saffron) #34

This is where it is super tricky, I have yet to see one kaplan meier curve, comparing DFMO to a cohort without it. The results cover 2 years when generally publications look at a 3 year mark.

No results are published in a peer reviewed in a journal.

Yes, there may be something in it, but it is difficult to tell.

Keep in mind, for internationals, a DFMO decision is not a cheap one, it can easily cost you 200 thousand dollars for a drug that is readily available in your own country.

CHOP who have done a lot of research in the DFMO area have not commented publicly on the trial.

(Sam Saffron) #35

I have sent an email to CHOP (Dr. Maris and Hogarty).

Both of them have spent an enormous amount of time researching NB and are trialing DFMO in a relapse setting at higher dosages in combination with chemo.

Dr. Hogarty said: “I work rather closely with both Drs. Ziegler and Park so don’t have anything to add to their sentiments.” so he is basically echoing the same exact concerns by Dr. Ziegler

I had a phone call with Dr. Maris who re-iterated all of the concerns. This is not a trial Dr. Maris would recommend to any of his patients.

I don’t think anyone here is “intentionally misleading the community” but I also don’t think there is enough science here to back anything up. All we have is anecdotal evidence.

(Alexey) #36

Not sure of where to put this recent article…

(Sam Saffron) #37

Neuroblastoma CA just posted an article on DFMO

(Kyle Matthews) #38

We hope to have sites open in Canada soon.

(Riza) #39

Hello, is there any paper published recently for the result of DFMO trials?

(Sam Saffron) #40

I think @Patrick_Lacey would probably have access to all the latest news here @Riza (pinged him just in case)