Raadpleeg ook de lijst van niet-toxische ondersteuning bij prostaatkanker van arts-bioloog drs. Engelbert Valstar.

En als donateur kunt u ook korting krijgen bij verschillende bedrijven, waaronder bij Medpro voor o.a. prostasol  een veelgebruikt natuurlijk middel bij prostaatkanker als alternatief voor hormoontherapie.


10 augustus 2022: Bron: Journal of Radiation Oncology volume 4pages377–386 (2015)

Zelfmoordgentherapie geeft uitstekende overall overleving voor prostaatkankerpatiënten.

Onderzoekers van het Houston Methodist Hospital (TX, VS) hebben al in 2015 opmerkelijk goede resultaten gepubliceerd van een langdurige studie naar radiotherapie - bestralingstherapie in combinatie met een zogeheten 'zelfmoordgentherapie' bij prostaatkankerpatiënten. De resultaten uit de studie laten een algehele 5-jaarsoverleving zien van 97% en 94% in twee patiëntengroepen, wat volgens deze onderzoekers een verbetering is van de mediane overall overleving (resp. met 20% in vergelijking met resultaten uit eerdere studies met radiotherapie en hormoontherapie bij dezelfde groep van patiënten. Geen aantoonbaar recidief na vijf jaar was 94 procent voor groep A en 91 procent voor groep B. De totale overleving na vijf jaar (OS) was 97 procent voor groep A en 94 procent voor groep B.

Wat hebben deze onderzoekers gedaan?

Tussen 1999 en 2003 namen 66 patiënten deel aan een fase II-studie en werden ze in twee groepen gesplitst: groep A bestond uit patiënten met niet uitgezaaide prostaatkanker (groep A; T1–T2a, Gleason score <7, pretreatment PSA <10)) en groep B bestond uit patiënten met een meer agressieve vorm van prostaatkanker, (T2b–T3, Gleason score ≥7, pretreatment PSA ≥10).

De lokaal toegediende gentherapie (GT) bestond uit een intraprostatische injectie van een adenovirale vector (adeno verkoudheidsvirus) die herpes simplex thymidinekinase  (ADV/HSV-tk) bevat, gevolgd door valaciclovir, een veel gebruikt medicijn tegen herpes.  Met als doel dat de valaciclovir het immuunsysteem van de patiënt zou stimuleren om actief de tumorcellen te vernietigen. Met de IMRT (intensiteit gemoduleerde radiotherapie) werd een gemiddelde dosis van 76 Gy de prostaat bestraald.

E Brian Butler, senior auteur en voorzitter van de afdeling Radiation Oncology van het Houston Methodist Hospital, legde eerder in een persbericht uit hoe deze zelfmoordgentherapie werkt: "We hebben strategisch een adenovirus gebruikt, vergelijkbaar met het virus dat verkoudheid veroorzaakt, om het therapiemiddel te dragen - een herpesvirusgen dat het enzym thymidinekinase (TK) direct in de tumorcellen produceert.
"Toen het herpesvirus-gen was afgeleverd en het TK begon te produceren, gaven we patiënten een veelgebruikt anti-herpesgeneesmiddel, valaciclovir. De combinatie viel het herpes-DNA aan en de TK-producerende tumorcellen vernietigden zichzelf, daarom wordt de procedure 'zelfmoordgentherapie' genoemd.

Patiënten met een laag risico (groep A; T1-T2a, Gleason-score <7, PSA vóór behandeling <10) werden behandeld met twee injecties met ADV/HSV-tk, elk gevolgd door valaciclovir en IMRT.
Patiënten met gemiddeld/hoog risico (groep B; T2b–T3, Gleason-score ≥7, PSA vóór de behandeling ≥10) werden behandeld met drie injecties met ADV/HSV-tk, elk gevolgd door valaciclovir, IMRT en hormonale therapie.

Aangezien het vaccin is gemaakt met de eigen kankercellen van de patiënt, heeft de behandeling het potentieel om de resultaten van standaardbestraling en hormonale therapieën aan te vullen en zelfs te verbeteren.
De onderzoeksresultaten rapporteerden opmerkelijk hoge recidiefvrije percentages op 5-jaars meting in beide groepen. Specifiek onthulden biochemische testen geen indicatie van terugkeer van kanker bij 62 patiënten.

Uit het abstract vertaald:

  • 66 patiënten (33 patiënten in elke groep) werden in de studie opgenomen. De mediane follow-up was 100 maanden.
  • De percentages vrij van falen (FFF), dus geen aantoonbaar recidief na vijf jaar waren 94 procent voor groep A en 91 procent voor groep B.
  • De totale overleving na vijf jaar (OS) was 97 procent voor groep A en 94 procent voor groep B. Negatieve biopsiepercentages na 24 maanden waren 83 procent voor groep A en 79 % voor groep B.

Bijwerkingen waren minimaal: Eén patiënt in groep B ontwikkelde een graad 3 verhoging van het leverenzym. Er was geen hematologische toxiciteit van graad 3 of hoger. Eén patiënt had graad 3 urogenitale toxiciteit. Er was geen graad 3 of hoger van lagere gastro-intestinale toxiciteit.

Het volledige studierapport is tegen betaling aan te vragen. Of vraag het studierapport op bij de hoofdonderzoeker: Correspondence to E. Brian Butler.

Hier het persbericht en het abstract van de studie:




Suicide gene therapy demonstrates remarkable prostate cancer survival rates 16 DEC 2015

Researchers at Houston Methodist Hospital (TX, USA) have reported ground-breaking results from a long-term clinical trial investigating radiation therapy combined with suicide gene therapy in prostate cancer.

The findings, published in the Journal of Radiation Oncology, reveal 5-year overall survival rates of 97 % and 94 % in two patient arms, demonstrating a 20% improvement for survival over previous studies.

Between 1999 and 2003, 66 patients participated in the Phase II clinical trial and were split into two arms: Arm A consisted of patients with cancer cells confined to the prostate and Arm B consisted of patients with more aggressive prostate cancer.

An experimental gene therapy termed ‘suicide gene therapy’ was given to patients in Arm A twice during the study alongside radiotherapy treatment. Arm B patients received suicide gene therapy three times during the study, alongside radiation and hormonal therapy.

E Brian Butler, senior author and Chair of the Department of Radiation Oncology at Houston Methodist Hospital explained how this suicide gene therapy works: “We strategically used an adenovirus, similar to the one that causes the common cold, to carry the therapy agent – a herpes virus gene that produces the enzyme thymidine kinase, or TK – directly into the tumor cells.

“Once the herpes virus gene was delivered and it started manufacturing TK, we gave patients a commonly used anti-herpes drug, valacyclovir. The combination attacked the herpes DNA, and the TK-producing tumor cells self-destructed, which is why the procedure is called ‘suicide gene therapy.”

Once activated, valacyclovir kills tumor cells, and alerts the patient’s immune system to induce an attack on the cancer.

Since the vaccine has been created with patient’s own cancer cells, the therapy has the potential to complement and even enhance results from standard-of-care radiation and hormonal therapies.

The study findings reported remarkably high 5-year freedom from failure rates across both arms of the study. Specifically, biochemical testing revealed no indication of cancer recurrence in 62 patients.

Eighty three percent of Arm A patients and 79% of Arm B patients demonstrated negative prostate biopsies, which were performed 24 months after treatment completion. Compared with radiotherapy alone, all evaluative factors exhibited significantly higher outcomes.

Bin Teh, lead author and Vice Chair of Houston Methodist’s Department of Radiation Oncology, explained that the majority of patients in the trial also experienced little or no side effects.

Currently a Phase III trial is underway to evaluate the safety and efficacy of the in situ immunomodulatory gene therapy before it can be approved by the US FDA.

Teh shared his enthusiasm for the future: “We firmly believe this will be a viable treatment strategy.”

Sources: Teh BS, Ishiyama H, Mai WY. Thompson TC, Butler EB. Long-term outcome of a phase II trial using immunomodulatory in situ gene therapy in combination with intensity-modulated radiotherapy with or without hormonal therapy in the treatment of prostate cancer. J. Radiat. Oncol. DOI: 10.1007/s13566-015-0239-y (2015); Houston Methodist press release

Long-term outcome of a phase II trial using immunomodulatory in situ gene therapy in combination with intensity-modulated radiotherapy with or without hormonal therapy in the treatment of prostate cancer


Abstract

Objective

The objective of this study is to report the long-term outcome of a phase II trial of immune-modulatory in situ gene therapy (GT) in combination with intensity-modulated radiotherapy (IMRT) with or without hormonal therapy for the treatment of prostate cancer.

Methods

GT was comprised of intraprostatic injection of adenoviral vector containing herpes simplex thymidine kinase (ADV/HSV-tk) followed by valacyclovir. A mean dose of 76 Gy was delivered to the prostate with IMRT. Low-risk patients (arm A; T1–T2a, Gleason score <7, pretreatment PSA <10) were treated with two injections of ADV/HSV-tk, each followed by valacyclovir, and IMRT. Intermediate/high-risk patients (arm B; T2b–T3, Gleason score ≥7, pretreatment PSA ≥10) were treated with three injections of ADV/HSV-tk, each followed by valacyclovir, IMRT, and hormonal therapy.

Results

Sixty-six patients (33 patients in each arm) were enrolled. The median follow-up was 100 months. Five-year freedom from failure (FFF) rates were 94 and 91 % for arms A and B, respectively. Five-year overall survival (OS) rates were 97 and 94 % for arms A and B. Negative biopsy rates at 24 months were 83 and 79 % for arms A and B. One patient in arm B developed grade 3 elevation in liver enzyme. There was no grade 3 or higher hematologic toxicity. One patient had grade 3 genitourinary toxicity. There was no grade 3 or higher lower gastrointestinal toxicity.

Conclusion

The combination of immunomodulatory in situ gene therapy and IMRT with or without hormonal therapy is feasible, safe, and effective in the treatment of prostate cancer. The effectiveness of this combined approach was likely through enhanced cytotoxicity, antitumor immune response, and abscopal effects. This approach with long term follow up appears to provide better clinical outcome over historical controls. A randomized trial of this strategy is currently ongoing.

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Acknowledgments

This work was supported by a specialized Program of Research Excellence (SPORE) grant (CA58204) from the National Cancer Institute, the Methodist Hospital Foundation, and the General Clinical Research Center (GCRC).

Author information

Authors and Affiliations

Corresponding author

Correspondence to E. Brian Butler.

Ethics declarations

Funding

This work was supported by NIH SPORE Grant P50-58,204. A specialized Program of Research Excellence (SPORE) grant (CA58204) from the National Cancer Institute, the Methodist Hospital Foundation, and the General Clinic Research Center (GCRC).

Conflicts of interest

The authors declare that they have no competing interests.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Bin S. Teh and Hiromichi Ishiyama contributed equally to this work.


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