1 december 2025:

Inmiddels zijn de resultaten van de IT-Matters studie, een fase III studie waarin Multikine, een Interleukin-IL-2 medicijn, als injectie vooraf aan immuuntherapie vooraf aan standaard zorg gepubliceerd. En blijkt de algehele overleving voor de Interleukin-IL-2 injectie sterk verbetert bij patiënten met een laag risico van lokaal gevorderde mond- en keelkanker type plaveiselcelcarcinoom en die eerder nog niet behandeld waren in vergelijking met standaardzorg. Op 5-jaars meting was er een verschil van mediaan 45 maanden langere overleving - 101,7 maanden vs 55,2 maanden tussen wel of geen IL-2 injectie naast standaard zorg.

Hier de resultaten vertaald uit het abstract:

Randomisatie 3:1:3 naar LI+/-CIZ (cyclofosfamide, indomethacine en zink) + SOC, of SOC (standaardzorg) alleen.
Met LI behandelde patiënten kregen 400 IE (als interleukine-2-equivalent; 200 IE peritumoraal, 200 IE perilymfatisch) sequentieel, dagelijks 5 dagen per week gedurende 3 weken vóór de operatie. Alle proefpersonen kregen SOC.
Na de operatie kregen patiënten met een laag risico op recidief radiotherapie, terwijl patiënten met een hoog risico gelijktijdig chemoradiotherapie kregen. De mediane follow-up was 56 maanden.
Er waren 923 ITT (Intent-to-Treat)-proefpersonen (380 ITT laag risico en 467 ITT hoog risico).
Objectieve vroege respons vóór de operatie (45 objectieve vroege respondenten; 5 complete responsen [CR's], 40 gedeeltelijke responsen [PR's], bevestigd door pathologie bij de operatie.
LI (+/- CIZ) had 8,5% objectieve vroege respondenten (45/529 ITT) en 16% objectieve vroege respondenten (34/212 ITT laag risico) versus geen gerapporteerde SOC objectieve vroege respondenten (0/394 ITT).
Objectieve vroege respondenten verlaagden het sterftecijfer significant tot 22,2% (ITT LI-behandeld), 12,5% (ITT laag risico LI + CIZ + SOC), terwijl het ITT laag risico SOC sterftecijfer 48,7% was. Dus, objectieve vroege respons beïnvloedde de algehele overleving (OS);
proportionele hazard ratio's waren 0,348 (95% BI: 0,152-0,801) voor ITT laag risico LI-behandeld, 0,246 (95% BI: 0,077-0,787) voor ITT laag-risico LI + CIZ + SOC. ITT laag-risico LI + CIZ + SOC toonde een significant OS-voordeel versus ITT laag-risico SOC (ongestratificeerde log-rank p = 0,048; Cox hazard ratio = 0,68; 95% BI: 0,48-0,95, Wald p = 0,024 [controle voor tumorstadium, tumorlocatie en geografische regio]).
Het absolute OS-voordeel nam in de loop van de tijd toe voor met ITT laag-risico (LI + CIZ + SOC) behandelde patiënten versus ITT laag-risico SOC: het bereikte 14,1% (62,7% versus 48,6%) na 60 maanden, met een mediaan OS-voordeel van 46,5 maanden (101,7 maanden versus 55,2 maanden).
Het voordeel in kwaliteit van leven voor complete responders hield > 3 jaar aan na LI-behandeling. Het percentage door de behandeling veroorzaakte bijwerkingen was vergelijkbaar tussen alle behandelde groepen. Er werden geen extra veiligheidsproblemen gemeld voor LI ten opzichte van SOC alleen na de operatie.

Het volledige studierapport is gratis in te zien. Klik op de titel van het abstract:

. 2025 Mar 21;31:1612084. doi: 10.3389/pore.2025.1612084

Neoadjuvant leukocyte interleukin injection immunotherapy improves overall survival in low-risk locally advanced head and neck squamous cell carcinoma –the IT-MATTERS study

Eyal Talor ^1,^*, József Tímár ², Philip Lavin ³, John Cipriano ¹, Dusan Markovic ⁴, Andrea Ladányi ⁵, Andrey Karpenko ⁶, Igor Bondarenko ⁷, Srboljub Stosic ⁸, Hrvoje Sobat ⁹, Aliaksandr Zhukavets ¹⁰, Nazim Imamovic ¹¹, Chih-Yen Chien ¹², Magdalena Bankowska-Wozniak ¹³, Mihály Kisely ¹⁴, Rajko Jovic ¹⁵, James Edward Massey Young ¹⁶, Sheng-Po Hao ¹⁷, The IT-MATTERS Study Working Group

PMCID: PMC11968324 PMID: 40191245

Abstract

The randomized controlled pivotal phase 3 study evaluated efficacy and safety of neoadjuvant complex biologic, Leukocyte Interleukin Injection (LI), administered for 3 consecutive weeks pre-surgery, in treatment naïve resectable locally advanced primary squamous cell carcinoma of oral cavity and soft palate. Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. LI-treated patients received 400 IU (as interleukin-2 equivalent; 200 IU peritumorally, 200 IU perilymphatically) sequentially, daily 5 days/week for 3 weeks before surgery. All subjects were to receive SOC. Post-surgery, patients with low risk for recurrence were to receive radiotherapy, while those with high risk received concurrent chemoradiotherapy. Median follow-up was 56 months. There were 923 ITT (Intent-to-Treat) subjects (380 ITT low-risk and 467 ITT high-risk). Pre-surgery objective early response (45 objective early responders; 5 complete responses , 40 partial responses , confirmed by pathology at surgery. LI (+/− CIZ) had 8.5% objective early responders (45/529 ITT) and 16% objective early responders (34/212 ITT low-risk) vs. no reported SOC objective early responders (0/394 ITT). Objective early responders significantly lowered death rate to 22.2% (ITT LI-treated), 12.5% (ITT low-risk LI + CIZ + SOC), while the ITT low-risk SOC death rate was 48.7%. Thus, objective early response impacted overall survival (OS); proportional hazard ratios were 0.348 (95% CI: 0.152–0.801) for ITT low-risk LI-treated, 0.246 (95% CI: 0.077–0.787) for ITT low-risk LI + CIZ + SOC. ITT low-risk LI + CIZ + SOC demonstrated significant OS advantage vs. ITT low-risk SOC (unstratified log-rank p = 0.048; Cox hazard ratio = 0.68; 95% CI: 0.48–0.95, Wald p = 0.024 [controlling for tumor stage, tumor location, and geographic region]). Absolute OS advantage increased over time for ITT low-risk (LI + CIZ + SOC)-treated vs. ITT low-risk SOC: reaching 14.1% (62.7% vs. 48.6%) at 60 months, with 46.5 months median OS advantage (101.7 months vs. 55.2 months), respectively. Quality of life benefit for complete responders sustained for >3 years post LI treatment. Percent treatment-emergent adverse events were comparable among all treated groups. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35.

12 juli 2012: hieronder het abstract van onderstaande studie. Ik weet dat John Jacobs afgelopen jaren heel veel meer onderzoek heeft uitgevoerd: op deze website staat al zijn onderzoek

Ook het volledige studierapport van onderstaande studie is tegen betaling in te zien op de website van Nature - Clinical Oncology

Cancer Immunol Immunother. 2005 Aug;54(8):792-8. Epub 2004 Dec 31.

Treatment of stage III-IV nasopharyngeal carcinomas by external beam irradiation and local low doses of IL-2.

Jacobs JJ, Hordijk GJ, Jürgenliemk-Schulz IM, Terhaard CH, Koten JW, Battermann JJ, Den Otter W.

Source

Department of Pathobiology, Utrecht Medical Centre, Yalelaan 1, P.O.Box 80.158, 3508 TD, Utrecht, The Netherlands.

Abstract

The therapeutic effect of intratumoural application of Interleukin-2 (IL-2) was studied in patients with stage III-IV nasopharyngeal carcinoma (NPC) that received radiotherapy. Patients with stage III-IV NPC receiving a standard treatment of 7,000 cGy external beam irradiation have a mean disease-free survival of about 1.5 years. In this paper, we describe ten of these patients who were treated with additional peritumoural and intratumoural injections with 3 x 10(4) U IL-2 on 5 days in weeks 2, 4, and 6 of the 7-weeks' irradiation period. This combined treatment group was compared with a historical group of patients treated with standard irradiation alone. Local IL-2 therapy showed a marked clinical and statistical significant improvement of disease-free survival. After 5 years, 63% of the IL-2 treated patients were disease-free versus 8% of the control patients. These results suggest that the therapeutic results of radiotherapy can be significantly improved by combining it with local IL-2 treatment. To our knowledge, this is the first clinical report showing that local IL-2 therapy is effective against an infiltrative and locally metastasizing tumour in human patients.

PMID:: 15627211; [PubMed - indexed for MEDLINE]

14 november 2005: Bron: Cancerimmunotherapy

Nederlandse onderzoekers in Utrecht hebben een trial met 10 patiënten met neus- en keeltumoren zeer succesvol behandeld met direct injecteren van Interleukin 2. De vijfjaarsoverleving bij deze kleine groep van patiënten, die vaak inoperabel zijn, steeg uiterst spectaculair van 8% bij alleen radiotherapie(bestraling) naar 63% bij het direct injecteren van interleukin 2 in de tumoren in het neus- en keelgebied.

Treatment of advanced nasopharyngeal carcinoma with only radiotherapy has a poor prognosis Nature clinical practices oncology highlights a research paper from Cancer Immunology Immunotherapy. Jacobs and co-workers from Utrecht University, the Netherlands, publish a remarkable improvement of standard radiotherapy. Addition of interleukin 2 injections increases the 5-years disease-free survival from 8% (radiotherapy only) to 63% (combination therapy). Its location makes nasopharyngeal carcinoma difficult to access for surgery. In advanced stages surgery is impossible due to tumour growth in vital parts of the head, like the encephalic trunk. The tumour can be reached with injections containing interleukin 2. Starting 1989, Prof. Den Otter and his group are successful in research of local interleukin 2 therapy of cancer. The activated immune system makes interleukin 2. In animal experiments, diseased animals and human, local interleukin 2 has resulted almost without any side effects, in higher percentage of cures that standard treatment. Local interleukin 2 therapy was successful in experimental animals with different kinds of advanced cancer. Local interleukin 2 has almost no side effects and is much cheaper than radio- or chemotherapy. Its consequence is, unfortunately, that local interleukin 2 is less interesting for pharmaceutical companies. Research with patients was limited to recurrent bladder carcinoma. The current paper adds nasopharyngeal carcinoma to this list A follow-up study with larger number of nasopharyngeal carcinoma patients is planned, in which local interleukin 2 is tested as addition to the newest standard therapy, a combination of radiotherapy and chemotherapy. The research group also intends to do research on patients with other kinds of cancer with a poor prognosis. More information on the research group and their research can be found at this website (www.cancerimmunotherapy.net).

immuuntherapie, keelkanker, mondkanker, neuskanker, interleukin-2, hoofd- halskanker, Multikine, overall overleving, radiotherapie