10 augustus 2018: Zoekend naar een antwoord n.a.v. een vraag onderaan dit artikel waar Xerecept verkrijgbaar is en dat Nederlandse oncologen nog nooit hiervan hebben gehoord kwam ik bij de publicatie van de resultaten van de fase III studie (klik op de tital): Steroid-Sparing Effect of Corticorelin Acetate in Peritumoral Cerebral Edema Is Associated With Improvement in Steroid-Induced Myopathy

Uit het studieprotocol krijg ik dit contactadres

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Lynn Adler
(650) 725-8630

De resultaten uit het abstract:

One hundred patients received subcutaneous injections of 1 mg twice per day of CrA and 100 patients received placebo for the duration of the study period. Although results did not attain statistical significance (at the P < .05 level), a clinically important difference in the proportion of responders between the CrA group (57.0%) and the placebo group (46.0%; P = .12) was observed. In addition, the maximum percent reduction in DEX dose achieved during the double-blind 12-week study was significantly greater in the CrA group (62.7%) than in placebo group (51.4%; P < .001). Patients receiving CrA demonstrated an improvement in myopathy and were less likely to develop signs of Cushing syndrome.

CrA enables a reduction in steroid requirement for patients with PBE and is associated with a reduction in the incidence and severity of common steroid adverse effects, including myopathy.

14 april 2017: Ik kreeg van David de vraag of en waar Xerecept verkrijgbaar is. Ik heb hem daarop het volgende antwoord gegeven:

Beste David, Xerecept is een ontstekingsremmer en zal net als dexamethason het bijkomende vocht verminderen. Maar uw behandelend arts zal dit ongetwijfeld ook weten. Met Xerecept loopt een fase III studie en wellicht kan uw arts daar informeren? https://med.stanford.edu/clinicaltrials/trials/NCT00088166

Hier een reviewstudie uit 2009/2011 maar moet voor worden betaald. Maar uw arts heeft meestal vrije toegang: http://www.tandfonline.com/doi/full/10.1517/13543780903190689?scroll=top&needAccess=true

Ik vind deze studie de beste en meest recente. maar ik denk niet dat u als leek hier verder mee kan. maar wellicht kunt u deze studie voorleggen aan uw behandelend arts? : Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136308/

Tekst loopt verder onder grafiek

Xerecept

21 juli 2012: Bron: 2011 May 15;17(10):3282-92. Epub 2011 Mar 8.

Mensen met een hersentumor krijgen meestal dexamethason om vorming van ontstekingsvocht in de hersenen tegen te gaan. Echter dexamethason geeft vaak ook bijwerkingen. Xerecept is een middel ter vervanging van dexamethason dat bewezen heeft een prima alternatief te zijn. Nu blijkt xerecept ook veilig te gebruiken bij kinderen: bron: Marketwatch 

Data presented today by Dr. Stewart Goldman M.D of the Children's Memorial Hospital, Chicago at the International Symposium for Pediatric Neuro-Oncology being held in Toronto, Canada showed encouraging positive results from a Phase I/II study of Xerecept in Pediatric Patients with Peritumoral Cerebral Edema (brain tumors).

Xerecept(R) is an investigational new drug for use in pediatric patients who are dependent on the steroid Decadron (dexamethasone) to treat peritumoral brain edema associated with cerebral tumors. Approximately 4,000 cases of pediatric brain tumors are diagnosed each year in the United States. Data from this Phase I/II study showed that Xerecept(R) was safe and well tolerated at all doses levels in these patients. Initial indications are that the drug can reduce or eliminate the need for Decadron, and the steroid-associated side effects, providing significant quality of life improvements.

The latest study, involving 15 children, was conducted by Stewart Goldman M.D. at Children's Memorial Hospital in Chicago, IL and Mark Kieran M.D. at Dana-Farber Cancer Institute in Boston, MA. All of the children enrolled on the study had severe steroid-induced side effects and had been unable to decrease dexamethasone dosing in spite of two attempts to do so by the attending physicians.

Corticosteroids (predominantly dexamethasone), the current standard treatment of peritumoral brain edema associated with cerebral tumors, have severe side effects such as severe myopathies, muscle wasting, morbid weight gain, osteoporosis, gastritis, gastrointestinal bleeding, hypertension and personality changes. These side effects are accentuated in pediatric patients, with substantial impact on the patient's ability to function in daily life.

"For those of us who treat children with brain tumors in our daily practice, the prospect of a safe and effective alternative to corticosteroids to control edema in these patients is indeed exciting", said Dr. Stewart Goldman, Children's Memorial in Chicago.

Of the 14 evaluable patients, all were able to reduce dexamethasone usage including 10 who reduced their dose by more than 50%, and five of the 10 were able to completely cease using steroids. 88% of patients on Xerecept(R) for at least six weeks reduced dexamethasone to less than 1mg. Those patients treated with Xerecept(R) at the daily maximum dose of 60ug/kg/day for longer than six weeks stopped decadron completely for over twelve weeks on average. These reductions in steroid dosing occurred despite progressive disease in all patients.

Xerecept(R) dosing not only had positive effects on the steroid-associated side effects, but was also associated with significant improvements in physical and emotional functioning and fatigue, as measured by use of the PedsQL(TM), a quality of life instrument which has been validated for use in pediatric patients with cerebral tumors.

Hier het abstract van de laatste gerandomiseerde placebo gecontroleerde fase III studie: Comparison of corticotropin-releasing factor, dexamethasone, and temozolomide: treatment efficacy and toxicity in U87 and C6 intracranial gliomas. 

Onderaan referentielijst van studies gerelateerd aan dit onderwerp

hCRF - Xerecept was more effective than either dexamethasone or temozolomide in the treatment of U87 xenografts, and results included improved prognosis with long-term survivors and only mild toxicity

Comparison of corticotropin-releasing factor, dexamethasone, and temozolomide: treatment efficacy and toxicity in U87 and C6 intracranial gliomas.

Source

Department of Neurology and Radiology, Sloan Kettering Institute Molecular Pharmacology and Chemistry Program, Inc, New York, NY 10065, USA.

Abstract

PURPOSE/

EXPERIMENTAL DESIGN:

Treatment of cerebral tumors and peritumoral brain edema remains a clinical challenge and is associated with high morbidity and mortality. Dexamethasone is an effective drug for treating brain edema, but it is associated with well-documented side effects. Corticorelin acetate (Xerecept) or human corticotrophin-releasing factor (hCRF) is a comparatively new drug and has been evaluated in two orthotopic glioma models (U87 and C6), by a direct comparison with dexamethasone and temozolomide.

RESULTS:

In vitro combination therapy and monotherapy showed a variable response in 6 different glioma cell lines. In vivo studies showed a dose-dependent effect of hCRF (0.03 and 0.1 mg/kg q12h) on survival of U87 intracranial xenograft-bearing animals [median survival: control--41 days (95% CI 25-61); "low-hCRF" 74.5 days (95% CI 41-88); "high-hCRF" >130 days (95% CI not reached)]. Dexamethasone treatment had no effect on survival, but significant toxicity was observed. A survival benefit was observed with temozolomide and temozolomide + hCRF-treated animals but with significant temozolomide toxicity. C6-bearing animals showed no survival benefit, but there were similar treatment toxicities. The difference in hCRF treatment response between U87 and C6 intracranial gliomas can be explained by a difference in receptor expression. RT-PCR identified CRF2r mRNA in U87 xenografts; no CRF receptors were identified in C6 xenografts.

CONCLUSIONS:

hCRF was more effective than either dexamethasone or temozolomide in the treatment of U87 xenografts, and results included improved prognosis with long-term survivors and only mild toxicity. The therapeutic efficacy of hCRF seems to be dependent on tumor hCRF receptor (CRFr) expression. These results support further clinical assessment of the therapeutic efficacy of hCRF and levels of CRFr expression in different human gliomas.

©2011 AACR.

PMID:
21385926
[PubMed - indexed for MEDLINE]
PMCID:
PMC3131845

References - Xerecept

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Plaats een reactie ...

2 Reacties op "Xerecept blijkt beter en geeft minder bijwerkingen dan dexamethason als aanvulling bij behandelingen van hersentumoren."

  • W Burhenne :
    Waarom is dit middel nog niet in Nederland verkrijg baar. Heb een aantal artsen hierover verteld maar zij zijn niet op de hoogte van het bestaan van deze medicatie.
    • Kees Braam :
      Beste mevrouw of meneer Bruhenne, ik heb het artikel van een update voorzien met daarin een adres van de contactpersoon van de fase III studie. Wellicht weten zij waar het medicijn te verkrijgen is of hoe te maken?
      Hier het telefoonnummer: Lynn Adler (Amerikass net nummer gebruiken)
      (650) 725-8630

      Een contactformulier staat in het artikel hierboven.

      Ik hoop dat u hier voldoende aan hebt.

      Kees Braam
      webmaster

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