6 augustus 2018: Bron: Cancer Manag Res. 2018; 10: 207–216. Published online 2018 Feb 1.

Tumoren van de weke delen is, als het niet operabel is (of met radiotherapie onschadelijk wordt gemaakt) en er een recidief ontstaat, heel moeilijk te behandelen. Chemokuren post operatief lijken weinig zin te hebben.  In 2015 publiceerde UZ Leuven een grote studie met eribulin myselate (Halaven) wat min of meer als een doorbraak werd gezien met enkele maanden verbetering van de mediane overall overleving.

Patiënten met een kwaadaardige tumor in spier- of vetcellen (wekedelensarcoom) hebben maar een beperkte levensverwachting, vaak zelfs minder dan één jaar. Een grootschalig onderzoek onder leiding van professor Patrick Schöffski van UZ Leuven wijst nu uit dat het middel eribulin (Halaven®) de levensverwachting significant doet toenemen. Een grote stap voorwaarts nadat de afgelopen decennia nauwelijks doorbraken geweest zijn op het vlak van de behandeling.

Professor Schöffski publiceerde de resultaten van een grootschalig onderzoek, waaruit blijkt dat patiënten die het geneesmiddel eribulin toegediend kregen, twee maanden langer in leven bleven dan de controlegroep die een behandeling met een oud product, decarbazine, kregen.>>>>>lees het artikel verder

Maar wat zijn enkele maanden op een heel leven. Weke delen tumoren komen vooral voor bij jonge mensen dus is een verbetering van enkele maanden in feite niets.

Recent is een reviewstudie verschenen over de stand van zaken bij weke delen tumoren met de focus op eribulin mesytate (Halaven) en in deze reviewstudie zijn de auteurs wel optimistisch en zeggen hoop te hebben voor patiënten met weke delen tumoren. Al zie ik niet zo snel waar dat optimisme dan vandaan komt behalve dan dat circa 70 procent geneest van weke delen tumoren met een standaard behandeling van operatie en/of bestraling - radiotherapie. Maar zodra er een recidief ontstaat is er geen genezende behandeling voorhanden tot nu toe.

Hieronder het werkingsmechanisme van eribulin mysetate dat bij o.a. borstkanker met botmetastases wel hele goede resultaten heeft laten zien

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Figure 1

Molecular structures of halichondrin B and eribulin.

Note: Reproduced from National Center for Biotechnology Information. Pubchem Open Chemistry Database –Compound Summary for CID 11354606. https://pubchem.ncbi.nlm.nih.gov/compound/11354606,13 and https://pubchem.ncbi.nlm.nih.gov/compound/5488895.14

In onderstande tabel staan een aantal studies vermeld met eribulin bij weke delen tumoren. Klik op de referentienummers om bij de studiepublicaties te komen. De referentielijst staat ook onderaan dit artikel:

Table 1

Summary of Phase I, Phase II, and Phase III clinical trials of eribulin in soft tissue sarcoma

AuthorsPatients on eribulinAdministration
ToxicityGradeNumber of patients*
TypeFrequencyCycle duration
Phase I DLT MDT
Synold et al59 40 Bolus D1,8,15 q28d FN 3 1 1.4 mg/m2
Neutropenia 4 1
Goel et al37 32 1 h infusion D1,8,15 q28d Neutropenia 4 2 1.0 mg/m2
Fatigue 3 1
Neutropenia 3 3
Tan et al38 21 1 h infusion D1 q21d FN 4 3 2.0 mg/m2
Mukohara et al39 15 2–10 min infusion D1,8 q21d Neutropenia 4 1 2.0 mg/m2
FN 3 1
Phase II Dose
Schöffski et al46 127 2–5 min infusion D1,8 q21d Neutropenia 3 66 1.4 mg/m2
Leukopenia 3 44
Anemia/fatigue 3 9
Kawai et al47 51 2–5 min infusion D1,8 q21d Neutropenia ≥3 44 1.4 mg/m2
Leukopenia ≥3 38
Lymphopenia ≥3 17
Anemia ≥3 7
FN ≥3 4
Phase III Dose
Schöffski et al17 226 2–5 min infusion D1,8 q21d Neutropenia ≥3 80 1.4 mg/m2
Leukopenia ≥3 23
Anemia ≥3 18
Fatigue ≥3 7
Hypokalemia ≥3 6

Notes: Dose-limiting toxicity and maximum tolerated toxicity in Phase I and toxicity in Phase II and III studies; route of administration was intravenous.

*The actual number of patients who received eribulin in the trial who had toxicity ≥3. Gray shading indicates that the data apply only to Phase I trial toxicity.

Abbreviations: DLT, dose-limiting toxicity; MDT, maximum tolerated toxicity, FN, febrile neutropenia; q21d, cycle of 21 days; q28d, cycle of 28 days; D1, day 1 of the cycle; D1,8, days 1 and 8 of the cycle; D1,8,15, days 1, 8, and 15 of the cycle.

Uit de conclusie van de auterus van deze reviewstudie is nog heel veel onzeker en ik deel hun optimisme eigenlijk niet. Ook zij zijn heel voorzichtig.

Conclusie

De eribulinestudie is de eerste fase III studie van de afgelopen jaren die een klinisch significant, zij het gematigd, overlevingsvoordeel heeft aangetoond bij de behandeling van geavanceerde STS van Liposarcoemen (LPS), en deze resultaten worden als bemoedigend beschouwd. Verschillen tussen de resultaten van progressievrije ziekte (PFS) en overall overleving (OS) blijven echter moeilijk uit te leggen. Eribulin is onlangs door de Amerikaanse FDA en EMA goedgekeurd voor de behandeling van geavanceerde Liposarcomen bij patiënten die voorbehandeld zijn met anthracycline-chemotherapie.
58

Er kan worden gesteld dat de kosteneffectiviteit van het geneesmiddel een potentieel obstakel zou kunnen zijn voor wijdverbreid gebruik van eribulin, en dit is wel vereist om te worden onderzocht in vervolgonderzoeken, waaronder metingen van de kwaliteit van leven. Een Fase III-studie heeft echter een significant overlevingsvoordeel aangetoond en een voor de hand liggende vraag is de mogelijke rol van eribulin in de neoadjuvante / adjuvante setting en de rol ervan in de eerstelijns setting in vergelijking met anthracyclinetherapie bij LPS-patiënten.17

Verdere studies zijn vereist vooral in het evalueren van vermeende biomarkers voor de respons op eribulin en de rol van dit middel in een vroeg stadium van de ziekte.

Het volledige studierapport: Advances in the treatment of soft tissue sarcoma: focus on eribulin is gratis in te zien.

Hier het abstract van de studie met bijbehorende referentielijst

In this article, we reviewed evidence from the latest published data on eribulin and its use in the treatment of soft tissue sarcomas. We explored the drug’s mechanism of action, pharmacodynamics, pharmacokinetics, and metabolism. Lastly, we reviewed all preclinical studies as well as clinical trials that investigated eribulin.

Cancer Manag Res. 2018; 10: 207–216.
Published online 2018 Feb 1. doi:  10.2147/CMAR.S143019
PMCID: PMC5798537
PMID: 29440930

Advances in the treatment of soft tissue sarcoma: focus on eribulin

Abstract

Eribulin mesylate is a synthetic derivative of halichondrin B isolated from a marine sponge. Its mechanism of action is through microtubule inhibition, which is different from that of taxanes. Eribulin has been approved for the treatment of metastatic breast cancer and more recently for non-operable or metastatic liposarcoma in patients who have received prior anthracycline chemotherapy. The major side effects of eribulin are bone marrow suppression including neutropenia, leukopenia, anemia, and fatigue/weakness, which can be well managed. In this article, we reviewed evidence from the latest published data on eribulin and its use in the treatment of soft tissue sarcomas. We explored the drug’s mechanism of action, pharmacodynamics, pharmacokinetics, and metabolism. Lastly, we reviewed all preclinical studies as well as clinical trials that investigated eribulin.

Disclosure

The authors report no conflicts of interest in this work.

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