UMC Utrecht start studie (i-GO studie ) met chemo via nanodeeltjes plus MR-HIFU voor borstkankerpatienten

Zie in gerelateerde artikelen een aantal andere artikelen over MR-HIFU.

13 november 2022: UMC-Utrecht, i-GO studie

In de i-GO studie onderzoeken we voor de eerste keer de combinatie van chemotherapie verpakt in temperatuurgevoelige nanodeeltjes (ThermoDox) en MR-HIFU (MRI-geleide opwarming met High Intensity Focused Ultrasound) bij vrouwen met een tumor in de borst en uitzaaiingen in de rest van het lichaam.

Dat deze i-GO studie nog als nieuw wordt gepresenteerd zegt veel over hoe weinig interesse er is voor niet invasieve behandelingen bij kanker. Jarenlang en dan spreek ik echt over 15 jaar of langer is deze techniek van MR-HIFU (artikel uit 2014 in het NtvG) al onderzocht, ook in Nederland. Ik ken een borstkankerpatiënte die steeds heeft geprobeerd om via MR-HIFU haar primaire borsttumor te laten verwijderen. Maar vergeefs. En nu heeft zij uitgezaaide borstkanker terwijl het 5 jaar geleden nog een lokale primaire tumor van enkele centimeters was.

Als je een google search doet (zie ook pagina 2 en 3) op het woord Thermodox dan kom je dus verschillende studies tegen waaronder dus ook de i-GO studie.

In deze reviewstudie wordt ThermoDox en MR-HIFU aan de hand van enkele studies besproken: Thermosensitive liposomes: a promising step toward localised chemotherapy

Klik op section 6 voor een overzicht van studies. Ook nog openstaande studies bij verschillende vormen van kanker.
Onderaan dit artikel staat het abstract plus referentielijst.

Een andere studie die eruitspringt is deze: Turning down the heat: The case for mild hyperthermia and thermosensitive liposomes

Ook deze studie is interessant om eens te lezen: To heat or not to heat: Challenges with clinical translation of thermosensitive liposomes

In deze studie is goed te lezen hoe ThermoDox werkt: Increased Duration of Heating Boosts Local Drug Deposition during Radiofrequency Ablation in Combination with Thermally Sensitive Liposomes (ThermoDox) in a Porcine Model

Ik kopieer een gedeelte van de tekst zoals die in het studieprotocol van de i-GO studie is vermeld:

i-GO studie :

Informatie over de i-GO-studieuitklapper, klik om te openen

Inleiding

In de i-GO studie onderzoeken we voor de eerste keer de combinatie van chemotherapie verpakt in temperatuurgevoelige nanodeeltjes (ThermoDox) en MR-HIFU (MRI-geleide opwarming met High Intensity Focused Ultrasound) bij vrouwen met een tumor in de borst en uitzaaiingen in de rest van het lichaam. Aan dit onderzoek zullen maximaal 12 patiënten met meedoen.

De standaard behandeling van uitgezaaide borstkanker bestaat uit chemotherapie, die vaak

via een infuus wordt toegediend. Meestal bestaat de chemotherapie uit twee middelen, namelijk doxorubicine en cyclofosfamide.

Nanodeeltjes

In dit onderzoek is één van de middelen, doxorubicine, verpakt in temperatuurgevoelige nanodeeltjes (liposomen), genaamd ThermoDox. Deze nanodeeltjes barsten open als zij opgewarmd worden. Alleen daar waar de ThermoDox verwarmd wordt, barsten de nanodeeltjes open, en komt er op die plaats een grote hoeveelheid doxorubicine vrij. In de rest van het lichaam (die niet verwarmd wordt) lekken de nanodeeltjes een beetje en komt er heel langzaam evenveel doxorubicine vrij als bij een normale behandeling. De cyclofosfamide wordt, zoals standaard is, na afloop via een infuus gegeven.

MR-HIFU

Het verwarmen van de tumor in de borst wordt gedaan met behulp van MR-HIFU. De MRI zorgt ervoor dat we precies kunnen zien waar de tumor in de borst zit. De HIFU bestaat uit sterke gebundelde ultrageluidsgolven die op de borsttumor worden gericht. Dit is vergelijkbaar met het bundelen van zonnestralen met een vergrootglas om zo een vuurtje te maken. De ultrageluidsgolven dringen door de huid heen, er hoeft dus niet in de borst gesneden te worden. Tijdens de behandeling is de patiënt onder sedatie (een soort lichte narcose).

Titel van het onderzoek

De i-GO studie: Behandeling van borstkanker door middel van chemotherapie verpakt in temperatuurgevoelige nanodeeltjes, in combinatie met lokale verwarming van de tumor.

Het doel van het onderzoek

Deze studie onderzoekt een nieuwe techniek om borstkanker zonder operatie te kunnen behandelen, ’opereren zonder snijden’ dus.
Uit eerder onderzoek weten wij dat er meer kankercellen doodgaan als de hoeveelheid chemotherapie die in de kanker komt groter is. De totale hoeveelheid chemotherapie die meestal via een infuus wordt toegediend is echter niet zomaar te verhogen; dan zouden de bijwerkingen in de rest van het lichaam te ernstig worden.
In de i-GO studie proberen wij de hoeveelheid chemotherapie in de borst zo hoog mogelijk te krijgen zonder dat de rest van het lichaam daar schade van ondervindt. In het i-GO onderzoek wordt de combinatie van MR-HIFU en Thermodox voor het eerst bij patiënten met borstkanker toegepast.
Het doel van het onderzoek is om vast te stellen of deze nieuwe vorm van behandeling veilig is en goed verdragen wordt. Ook wordt er gekeken of de tumor in de borst op de behandeling heeft gereageerd.

>>>>>>>>>lees verder het studieprotocol en wie er aan mag deelnemen.

Hier het abstract van een eerder genoemde reviewstudie uit juli 2022:

ABSTRACT

Introduction

Many small molecules and biologic therapeutics have been developed for solid tumor therapy. However, the unique physiology of tumors makes the actual delivery of these drugs into the tumor mass inefficient. Such delivery requires transport from blood vessels, across the vasculature and into and through interstitial space within a tumor. This transportation is dependent on the physiochemical properties of the therapeutic agent and the biological properties of the tumor. It was hoped the application of nanoscale drug carrier systems would solve this problem. However, issues with poor tumor accumulation and limited drug release have impeded clinical impact. In response, these carrier systems have been redesigned to be paired with targetable external mechanical stimuli which can trigger much enhanced drug release and deposition.

Areas covered

The pre-clinical and clinical progress of thermolabile drug carrier systems and the modalities used to trigger the release of their cargo are assessed.

Expert opinion

Combined application of mild hyperthermia and heat-responsive liposomal drug carriers has great potential utility. Clinical trials continue to progress this approach and serve to refine the technologies, dosing regimens and exposure parameters that will provide optimal patient benefit.

Article highlights

Appraisal of the pre-clinical data supporting triggered drug release from carriers
Description of heat producing modalities and their comparison
Appraisal of pre-clinical studies on hyperthermia induced drug release
Listing and appraisal of clinical trials of hyperthermia triggered drug release from liposomes

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a co-founder of Thermosome, a biotech start-up focused on developing temperature-sensitive liposomes for clinical use based on the synthetic phospholipid DPPG2. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

Authors RC and CCC were funded by the Engineering and Physical Sciences Research Council under programme grant EP/L024012/1 Oxford Centre for Drug Delivery Devices .

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