Terapia radioligandowa 177Lu & 225Ac PSMA

[zosia bluszcz]

Post zosi bluszcz przeniesiony z wątku Miszy:

Jako ciekawostka (potencjalnie ważna) jeszcze jedna informacja.
Zastrzegam tylko, że wiem na ten temat bardzo mało i proszę nie trzymać mnie za słowo. Od jednego z lekarzy słyszeliśmy (padło to jako jedna z opcji dalszego leczenia), że w CO Bydgoszcz niedługo (za 2/3 miesiące) ma pojawić się (niestety odpłatnie, duże kwoty) możliwość leczenia 177Lu-PSMA-617, czyli jednej z najnowszych metod celowanej walki z rakiem prostaty, która wydaje się przynosić doskonałe rezultaty. Koszta są bardzo duże, choć dobrze wiedzieć, że pojawia się kolejny nabój do walki.

Odplatne leczenie w panstwowym (?) szpitalu srodkiem, ktory jest ciagle w fazie badan?



German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

177Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration- resistant prostate cancer (mCRPC).
Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients.

Methods:
One hundred forty-five patients (median age, 73 y; range, 43–88 y) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1–4 therapy cycles and an activity range of 2–8 GBq per cycle.
Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician’s report.
The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline $ 50% from baseline to at least 2 wk after the start of RLT.

Results:
A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available.
The median follow-up was 16 wk (range, 2–30 wk).
Nineteen patients died during the observation period.
Grade 3–4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%.
The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle.
Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response.

Conclusion:
The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients.
Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.
https://www.snmmi.org/files/FileDownloads/JNM 1-17 featured article_Lu-177-PSMA-617 Therapy.pdf


Caly artykul:

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.pdf

Artykul dot. nieduzej kohorty niemieckiej (24 pacjentow):

Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer.pdf

Bardzo interesujacy australijski artykul na temat Lutetu 177 PSMA:

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer- a review of the current literature and discussion of practical aspects of therapy.pdf

W USA prowadzony jest obecnie nabor do badan klinicznych z uzyciem Lutetu 177:

Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC
https://clinicaltrials.gov/ct2/show/NCT03042468

oraz

Lutetium-177 (Lu177) Prostate-Specific Antigen (PSMA)-Directed EndoRadiotherapy (PSMA-directed EndoRadiotherapy of Castration-resISTant Prostate Cancer (PERCIST): A Phase II Clinical Trial)

https://clinicaltrials.gov/ct2/show/NCT03042312

[zosia bluszcz]

Post zosi bluszcz przeniesiony z wątku Źrebie:

po wstępnej rozmowie sugerowano terapię LU177 - wiecie coś na temat tego leku? Byłby skuteczniejszy niż Docetaksel x 6?

Terapia LU-177 (Peptide Receptor Radionuclide Therapy, PRRT) to leczenie zaawansowanego (przerzutowego) raka prostaty przy pomocy radioizotopu wydzielającego promieniowanie beta, ktore niszczy wylacznie komorki CaP z receptorami PSMA (kwalifikacja do leczenia wymaga wykonania PET-CT PSMA z uzyciem Ga68).


Ulotka informacyjna skierowana do australijskiego pacjenta:

LU-177 PSMA Therapy for Men with Advanced Prostate Cancer
UCMI | Uniting Care Medical Imaging

How Lutetium-177 PSMA therapy works
PSMA is a type of protein found on the surface of cells on the prostate gland. When someone has prostate cancer there is an increased amount of the PSMA protein on the cell. PSMA will also appear in other parts of the body where the prostate cancer has spread or metastasised. Lutetium-177 PSMA Therapy uses a molecule which attaches itself to the PSMA receptors on the cancer cells. Before it is administered, the PSMA molecule is bound with Lutetium-177, which emits beta radiation, a destructive type of radiation that damages the cancer cells when it is in close proximity to them. Over time it destroys the prostate cancer cells. The PSMA molecule acts as a means of transporting the radiation to the tumour site to damage and kill the cancer cells. As the PSMA travels to the tumour sites it only targets the unhealthy cells preventing radiation exposure to other parts of the body. This is often referred to as Peptide Receptor Radionuclide Therapy (PRRT)
https://ucmi.com.au/our-services/lu-177 ... te-cancer/

Patient Info LUTETIUM-177 PSMA Therapy-WEB.pdf

Sprawozdanie z zastosowania LU-177 u 100 pacjentow niemieckich z przerzutowym rakiem opornym na kastrację (mCRPC)

Clinical experience with 100 consecutive patients treated with Lu-177-labeled PSMA-I&T radioligand therapy for metastatic castration-resistant prostate cancer

Abstract

Background:
To report our clinical experience with 177Lutetium-labeled prostate-specific membrane antigen-ligand (177Lu-PSMA-I&T) for systemic radioligand therapy in 100 consecutive patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods:
All patients were treated under a review board-approved compassionate use protocol.
Eligibility criteria for 177Lu-PSMA-I&T therapy included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or unsuitability for taxanes as well as positive 68Ga-PSMA tracer uptake of metastases in a prior PET-scan.
Intravenous treatment with 177Lu-PSMA-I&T was given 6- to 8-weekly with an activity of 7.4GBq up to 6 cycles in patients without clinical or radiographic progression.

We report prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS) and overall survival (OS) as well as toxicity. Results: Median age was 72 years (range 46-85) and median PSA level was 164 ng/ml (range 0-6178).
Bone, lymph node and visceral metastases were present in 94%, 85% and 33% of patients, respectively.

The median number of previous treatment regimens for mCRPC was 3 (range 1-6) and 84% of patients were pretreated with chemotherapy

At the time of evaluation, 286 cycles with 177Lu-PSMA-I&T were applied (median 2 cycles per patient, range 1-6), while treatment was still ongoing in 27% of patients.
Overall, 4 and 6 cycles were applied in 33 and 15 patients, respectively. PSA decline ≥30%, ≥50% and ≥90% was achieved in 40%, 32% and 9% of patients, respectively.

Median PSA-PFS was 3.4 months (95%CI 2.7-4.0), median cPFS was 4.1 months (95%CI 2.5-5.7) and median OS was 12.2 months (95%CI 8.8-15.7).

Treatment-emergent hematologic grade 3/4 toxicities were anemia in 7%, thrombocytopenia in 5% and neutropenia in 4% of patients.
Grade 3/4-non-hematologic toxicities were not observed.
The main non-hematologic grade 1/2 toxicities were dry mouth in 18%, fatigue in 16% and loss of appetite in 9/% of patients.

Conclusions:
Radioligand therapy with 177Lu-PSMA I&T appears to be safe and active in late-stage mCRPC.

http://ascopubs.org/doi/abs/10.1200/JCO ... _suppl.206



Trudno powiedziec czy LU-177 bylby skuteczniejszy niz Docetaxel - o ile wiem nie bylo badan klinicznych, ktore porownywalyby dzialanie obu lekow.
LU-177 stosowany jest raczej jako leczenie drugiej i trzeciej linii u pacjentow z rakiem opornym na kastracje (mCRPC), ktorzy przeszli wczesniejsze, nieskuteczne leczenie ADT drugiej generacji (Abirateron, Enzalutamid), taksanami (Docetaxel, Cabazitaxel) lub Ra233.
Trudno rowniez powiedziec czy Zrebie zostalby zakwalifikowany do leczenia LU-177 - przed podjeciem decyzji o kwalifikacji Niemcy musieliby dysponowac pelna dokumentacje medyczną, w tym wynikami PET-CT PSMA Ga68.
Mysle, ze nalezy rozpoczac terapie DX a ewentualną terapię LU-177 w Berlinie zostawic na wypadek, odpukac, braku skutecznosci DX...
Z zyczeniami minimalnych skutkow ubocznych terapii,
zosia

[zosia bluszcz]

Post zosi bluszcz przeniesiony z wątku Capricorn(a):

Dowiedziałem się o rewelacyjnej metodzie leczenia raka o nazwie Lu177-PSMA, polegające na leczeniu izotopem lutetu.

Wedle mojej najlepszej wiedzy, nikt z uczestnikow forum nie byl leczony przy pomocy Lu 177-PSMA.
Leczenie tym specyfikiem zaproponowano w berlinskiej klinice Charite najmlodszemu chyba pacjentowi piszącemu na forum, zrebie (34 lata).
Zrebie terapii Lutetem w koncu się nie poddal - leczony jest obecnie Docetaxelem.


Ponizej wklejam artykul z 2017 roku na temat zastosowania Lu 177-PSMA u pacjentów z rakiem prostaty, z ktorego wynikaloby, że rowniez i tej terapii nie mozna okreslic mianem magic bullet

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Abstract
Prostate‐specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high‐binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.

Predictors of Response
Not all men with mCRPC will have a good treatment response to 177Lu PSMA. Up to a third of those men treated to date show progressive disease despite treatment. This is likely due to a variety of factors.

One important factor is whether the tumour cells uniformly express a high density of the PSMA receptor (Fig. 3). Heterogeneity of PSMA receptor activity within the tumour population may mean that some sites will not respond to treatment with 177Lu PSMA, which will manifest as disease progression, and a rising PSA.

Currently PSMA activity is measured by assessing intensity of activity on a 68Ga‐PSMA staging PET/CT and is a requirement for treatment in all currently published studies. Cutoffs of PSMA intensity on 68Ga‐PSMA below which 177Lu PSMA therapy may not be effective have not yet been established.

A recent study of 40 patients identified platelet level and the need for pain relief as the most significant predictor of poor response to 177LU‐PSMA, likely reflective of the burden of metastatic bone disease.26
This same study did not find that intensity of PSMA activity on 68Ga‐PSMA staging PET/CT was predictive of response, but this is likely because intense PSMA activity on 68Ga‐PSMA imaging was one of the inclusion criteria for receiving 177Lu PSMA therapy initially.26

Other studies have commented that bone metastases appear to respond less well than visceral or lymph nodal disease to treatment with Lu PSMA.3

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355374/





Dwa lata pózniej (artykul ASCO, luty 2019) Australijczycy są bardziej optymistyczni:

Radioligand Therapy Achieves Responses in Metastatic Prostate Cancer
In a prospective, single-center, single-arm phase II trial reported at the 2019 Genitourinary Cancers Symposium, a novel approach using a tumor-specific radioligand therapy that binds to prostate-specific membrane antigen (PSMA) (lutetium-177 PSMA-617 -[LuPSMA]) achieved responses in a majority of men with metastatic castration-resistant prostate cancer that had progressed on standard therapies.1
High prostate-specific antigen (PSA) response rates were observed with low toxicity in this heavily pretreated group of patients with aggressive disease.
High response rates were also found in men who were re-treated with LuPSMA after disease progression.
Although the study was not powered to look at survival, given the absence of a control arm, men who received LuPSMA lived a median of 13.3 months after treatment, exceeding the expected survival of 9 months in this setting.
https://www.ascopost.com/issues/march-1 ... te-cancer/



Sprawdzilam prowadzone w tej chwil badania kliniczne z Lu 177-PSMA:
- 2 są prowadzone w USA
- 1 w Australii (randomizowane, zaslepione, prównujące Lu 177 PSMA z Cabazitaxelem, wspomina o nim artykul ASCO zacytowany wyzej)
- 1 w Holandii, dla pacjentów z hormonozaleznym CaP i z nielicznymi przerzutami

Moze sprawdz ten Berlin?

pzdr
zosia

[zosia bluszcz]

Leczenie mCRPC przy pomocy Actinium-225 and Lutetium-177 w Centrum Radioterapii Molekularnej, Departament Medycyny Nuklearnej Uniwersytetu Saarland w Homburgu (DE)




PSMA-directed Radionuclide Therapy (PSMA-PRRT, PRLT) incl Actinium-225 and Lutetium-177

Prostate cancer is the most common malignant tumor affecting men in Germany. After local therapy (surgery and/or radiation) with the intention of curing advanced (metastatic) prostate cancer, a supplementary anti-hormone therapy is often initiated. After prolonged anti-hormone therapy (androgen-deprivation therapy, ADT), the tumor cells often become resistant, so that other chemotherapeutic treatment options are used as the tumor disease progresses. The uro-oncologists use the entire range of therapies for advanced prostate carcinoma.
PSMA-directed radionuclide therapy, also known as PSMA-directed peptide receptor radionuclide therapy (PSMA-PRRT or PRLT), is a new targeted therapy for patients with advanced prostate carcinoma. PSMA (prostate-specific membrane antigen) is a protein receptor that is richly present on the cell surface of prostate carcinoma cells. This is used for diagnostic and therapeutic procedures in Nuclear Medicine particularily for this tumor entity by means of theranostics, a radioactive nuclide coupled to a substance that binds to PSMA, which emits either detectable radiation for diagnostic purposes or (therapeutically) short-range harmful radiation (e.g. Lu177). During PSMA-directed radionuclide therapy, the radioactive radiation (ß-radiation) exerts its therapeutic effect directly on the tumor cells exposing minimal radiation on the surrounding healthy tissues.


Case Report I PSMA-Therapy

61y old male prostate carcinoma patient with bone metastases. Patient had progressive disease under ADT and abiraterone plus prednisolon. Three treatment cycles of PSMA-directed radioligand therapy (PRLT) using Lutetium-177 PSMA-617 resulted in a dramatic decline of PSA level. Follow-up therapy monitoring by 68Ga-PSMA-11 PET imaging showed only minor residual disease.


Indications for PSMA-directed radionuclide therapy (PSMA-PRRT, PRLT) with 177Lu (Lutetium) and/or 225Ac (Actinium)

Initially, the prostate carcinoma is usually surgically removed or irradiated with curative intent. Although the therapy is optimal, recurrence often occurs during the further course. If inoperable, this can usually be controlled for an extended period of time with anti-hormonal therapy (ADT, directed against prostate carcinoma-stimulating androgens). The tumor cells finally become insensitive (resistant) to these agents and continue to grow unhindered.
Solely bone involvement often offers the possibility of bone-directed radionuclide therapy (Alpharadin, Xofigo).
If this therapy is out of question or no longer effective, many patients will have to undergo chemotherapy. Although this can lead to side effects for the patient, it often leads to tumor control for some time. When the tumor cells finally become resistant to this treatment, PSMA-PRRT (PRLT) often still works because it provides targeted intense radiation of the tumor from the inside, sparing the healthy surrounding tissue because of the milimeter or submilimeter range of radiation. This is a new treatment method for patients for whom no satisfactory therapeutic alternatives are left. For an effective treatment, the metastases or tumor lesions should have the ability to accumulate PSMA in sufficient intensity. To determine this, a 68Ga PSMA PET/CT examination is performed as part of the theranostic concept prior to therapy. This PET-CT study is also offered by our department.



Homburg Concept of Tandem 225Ac (Actinium) and 177Lu (Lutetium) PSMA Radioligand Therapy (Alpha/beta Tandem PRLT)

We were able to show, that patients developing Lutetium (177Lu) refractory mCRPC disease, i.e. metastatic prostate cancer with insufficient response to 177Lu PRLT, may respond well to 225Ac-augmented 177Lu-PRLT. With our approach we use a low amount of activity of 225Ac together with standard 177Lu activities achieving superior remission rates with less toxicity as the standard 225Ac PRLT (mono Actinium PRLT) approach.


Case Report II PSMA-Therapy

A 77y old male prostate carcinoma patient showed progressive disease after enzalutamide and chemotherapy. Near complete remission after a single treatment of PSMA-directed radioligand therapy using Lutetium-177 PSMA-617. Therapy monitoring was performed by 68Ga-PSMA-11 PET imaging.


Therapy procedure

Following the preparing examinations (blood tests, quantitative assesment of organ functions, e.g. renal function, salivary gland function), the radionuclide substance is infused through the arm vein at a dose based on the tumor load and the test results. Prophylactic cooling maneuvers of the salivary glands (cooling of the parotid glands from outside) are performed, assuming appropriate for the patient's benefit. Also the infusion of fluids is provided for sufficient hydration (rinsing) .
During the inpatient stay, the radiation dose reached in tumor and the sensitive organs (especially kidney) is calculated. This is achieved by serial whole-body and SPECT-CT examinations, which allow quantification of the gamma radiation emitted out from the respective tissue. These measurements also involve blood sampling. The duration of the inpatient stay ranges from 2-4 days.


Side effects

In most cases the therapy is very well tolerated. Most patients do not report any noticed side effects. Occasionally there are adverse effects such as minor nausea or reduced appetite for days, taste disturbances or dry mouth (transient or permanent) as well as fatigue. The PSMA-binding radiopharmaceutical is excreted by the kidneys, liver and gallbladder. A normal intestinal activity is therefore required, otherwise stimulation of bowel movements may be considered. A minimum intake of liquids is necessary to ensure this. Liver and kidney values are checked further after therapy.
The organs susceptible to radiation-induced injury during this therapy are mainly the salivary and lacrimal glands, which are also rich in PSMA. Cooling of the salivary glands can possibly decrease the severity of radiation damage by means of decreased blood flow in these tissues. Nevertheless, the risk of permanent damage with loss of function (dry mouth) appears to be low with Lu-177 PSMA-PRRT unlike with other radionuclide therapies involving the salivary glands. However, the long-term side effect of dry mouth and/or dry eye cannot be entirely excluded. In addition, this treatment may lead to temporary changes in blood counts.


Case Report III PSMA-Therapy

84y old male prostate carcinoma patient with liver and bone metastases (mCRPC). Patient had progressive disease after androgen deprivation therapy (ADT), abiraterone/prednisolon, and radiation therapy. Full biochemical response (complete remission) was achieved by 3 treatment cycles of PSMA-directed radioligand therapy (PRLT) using Lutetium-177 PSMA-617. Therapy monitoring was performed by 68Ga-PSMA-11 PET imaging.


Expertise in Homburg; Centre of Molecular Radiotherapy, Dep. of Nuclear Medicine, Saarland University

The Department of Nuclear Medicine in Homburg with its Centre of Molecular Radiotherapy focuses on innovative theranostic treatment approaches in oncology. Prof. Ezziddin is a well recognized international expert in targeted radionuclide therapy and has developed various concepts for individualized cancer therapy, which is the main focus of his clinical and scientific efforts. His commitment is to optimize the treatment of advanced metastatic or otherwise difficult-to-treat cancer disease. After the introduction of Lu-177 based therapy in 2004, he pursued and published new concepts for increasing the effect, including intra-arterial and augmentation approaches. In order to optimize PSMA-directed radionuclide therapy, the Homburg group strives to take into account the individual binding properties and receptor capacity, the tumor load, as well as the patient's organ functions and excretion kinetics for therapy planning and decision making.

In Homburg, the Ezziddin working group established a standardized dosing scheme for individualized PSMA-directed (PRLT) and Somatostatin receptor-mediated PRRT. This allows for dose-escalation in difficult or highly advanced metastatic disease. Also, augmentation approaches with different anti-tumor substances and alpha-emitters (Ac225) for tandem PRLT have been succcessfully applied as one of the first centres worldwide.

It is important to emphasize that PSMA-PRRT is still an experimental new therapy for which long-term data are scarce. However, the initial results are so promising that this form of therapy cannot be withheld from patients in need. A temporary tumor mass reduction and tumor control is likely in the setting of good tumoral theranostic uptake and accumulation, however, after repeated treatment courses, this procedure may eventually be no longer able to stop tumor progression, as with all other procedures in the (incurable) metastasized stage of prostate cancer.

saarland.de/de/einrichtungen/kliniken_institute/radiologie/nuklearmedizin/patient_information_in_english/psma_directed_radionuclide_therapy_psma_prlt/

[jesien 2015]

Ośrodki w Niemczech leczące za pomocą Lutetium 177 PSMA

Szukałam jako " Lutetium 177 PSMA therapy in Germany."
Na poniższej stronie sa ośrodki uniwersyteckie i ceny.


https://bookinghealth.com/disease/lutet ... ma-therapy

Finski Docrates tez leczy mCRPC przy użyciu Lutetium177.

[leonardo556]

W czasie konsultacji u dr IS zapytałem o leczenie Sipuleucel-T. Doktor niespecjalnie chciała temat rozwijać, ale nadmieniła, że jej zdaniem aktualnie najbardziej obiecującą metodą leczenia zaawansowanego raka prostaty jest Lutet 177.

Na forum mamy wielu kolegów z rakiem hormonoopornym. Wydaje się, że Ramzej, Zbyszko i wielu innych powinno się bliżej zainteresować się tą metodą leczenia. W Niemczech terapia Lu 177 kosztuje kilkanaście tys EUR. Jeżeli ktoś uważa, że to drogo proponuję zastosować metodę "na koszt spadkobierców".

Wszelkie informacje o Lu 177 mile widziane.

Leonardo

[zosia bluszcz]

Obiecujące wyniki australijskiego badania klinicznego:



[177Lu]Lu-PSMA-617 vs Cabazitaxel in Patients With Metastatic Castration-Resistant Prostate Cancer
The Lancet


Abstract

BACKGROUND
Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer.
We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.

METHODS
We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia.
We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed.
Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans.
PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings.
Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6·0–8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline.
This trial is registered with ClinicalTrials.gov, NCT03392428.

FINDINGS
Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging.
Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel.

PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16–42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9–37]; p=0·0016).
Grade 3–4 adverse events occurred in 32 (33%) of 98 men in the [177Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group.
No deaths were attributed to [177Lu]Lu-PSMA-617.

INTERPRETATION
[177Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [177Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.



Advanced Prostate Cancer
Written by Oliver Sartor MD

This is an important trial; congratulations are due to the authors for executing an important prospective randomized study. This is good work.

The study by Michael Hofman and colleagues in Australia compared cabazitaxel with PSMA-617 lutetium-177 and enrolled patients who were considered to be PSMA-positive and, importantly, excluded patients who had FDG PET–discordant lesions.
A total of 291 people were screened for the trial and 91 patients were excluded either because predominantly they had either PSMA uptake that was insufficient for randomization or because they had FDG-discordant disease.

The patients included in the trial had to have failed a previous abiraterone- or enzalutamide-type novel hormonal agent, and progressive disease at the time of trial entry was required.

What was found was interesting in that, by a variety of endpoints including time to PSA progression and PSA response rate, as well as radiographic progression and time to image-based progression, those patients treated with the PSMA lutetium-177 had better outcomes.
Notably missing, however, was adequate survival information, making this trial quite provocative but not definitive, and it will not lead to regulatory approval as it was a randomized phase II trial.

The VISION trial with PSMA lutetium-177 in a similar setting of post abiraterone/ post docetaxel has now completed accrual, and the investigators anticipate having results later in 2021. This is a definitive phase III trial and could lead to regulatory approval should the results be positive.


https://www.practiceupdate.com/c/113763 ... d=20845155

[zosia bluszcz]

Jak się zabrać za szukanie możliwości leczenia Lutetem 177 w Polsce?
Znalazłem Vivantes

Zbyszko, proponujący terapię Lu177-PSMA ośrodek Vivantes znajduje się w Berlinie.


Informacja dot. terapii Lu177-PSMA zamieszczona na stronie szpitala:

Metoda Lu177-PSMA: diagnostyka i terapia w przypadku złośliwego nowotworu gruczołu krokowego w stadium zaawansowanym
U pacjentów z rakiem prostaty w stadium zaawansowanym, u których terapia hormonalna i chemioterapia przestały być skuteczne, nowoczesna terapia Lu177-PSMA może przynieść dobre efekty leczenia. W przypadku konwencjonalnych terapii naświetlane są najczęściej tylko przerzuty do kości. Terapia Lu177-PSMA jest wykorzystywana do leczenia pacjentów także z przerzutami do węzłów chłonnych i innych organów takich jak płuca lub wątroba.

PSMA (antygen błonowy swoisty dla prostaty) jest białkiem, które występuje na powierzchni komórek raka prostaty w namnożonej ilości. Dzięki medycynie nuklearnej udało się opracować dwie substancje, które w sposób precyzyjny przylegają do PSMA, ale nie przylegają do zdrowej tkanki: Gallium 68 – jako marker diagnostyczny – pokazuje nam w pozytonowej tomografii emisyjnej (PET) dokładny obraz guza i jego ewentualnych przerzutów.
Luthetium 177 – jako środek terapeutyczny – przyczepia się bezpośrednio do guza, nasyca go radioaktywnością i naświetla od wewnątrz.

Aby móc przeprowadzić leczenie z wykorzystaniem Lu177-PSMA, komórki rakowe pacjenta muszą wykazywać ekspresję PSMA. Stwierdza się to na podstawie obrazowania za pomocą gallium 68.
Większość naszych pacjentów dobrze znosi tę terapię, która ponadto jest obarczona nikłymi skutkami ubocznymi.

https://www.vivantes-international.com/ ... -vivantes/

Koszt leczenia wg info na stronie:
PET/TK od 2 200,00 €
Terapia radioligandem z wykorzystaniem ligandu LU-177-PSMA od 12 100,00 €

Ponieważ do tego trzeba doliczyć koszt samej hospitalizacji oraz koszt dodatkowych badań - w sumie koszt leczenia Lu-177 PSMA może rzeczywiście wynieść ok. 20 tys. EUR.




W marcu 2021 Novartis ogłosił wyniki badania klinicznego III fazy VISION: Lu-177 PSMA-617 w leczeniu pacjentów z zaawansowanym mCRPC, z pozytywnym skanem PET 68Ga PSMA, po uprzednim leczeniu taksanami oraz antyandrogenami II generacji w porównaniu z pacjentami leczonymi standardowo.



Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer

About VISION
Basel, March, 23, 2021 — Novartis today reported the first interpretable results of the Phase III VISION study evaluating the efficacy and safety of 177Lu-PSMA-617, a targeted radioligand therapy in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) compared to best standard of care alone.

The trial met both primary endpoints of overall survival and radiographic progression-free survival1, helping to move closer the ambition of becoming the targeted treatment for >80% of patients with advanced prostate cancer. The safety profile was consistent with data reported in previous clinical studies1.
Results from the VISION trial will be presented at an upcoming medical meeting and included in US and EU regulatory submissions.

VISION is an international, prospective, randomized, open-label, multicenter, phase III study to assess the efficacy and safety of 177Lu-PSMA-617 (7.4 GBq administered by i.v. infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen best standard of care in the investigational arm, versus best standard of care in the control arm17.

Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor-directed therapy (ARDT), were randomized in a 2:1 ratio in favor of the investigational arm. The alternate primary endpoints were rPFS and OS. The study enrolled 831 patients1.
https://www.novartis.com/news/media-rel ... ate-cancer




Informacja o badaniu klinicznym VISION figurująca na stronie clinicaltrials.gov:

Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer
https://clinicaltrials.gov/ct2/show/NCT03511664



W ramach badania klinicznego VISION pacjentom podawano 177Lu-PSMA-617 (7.4 GBq) dożylnie co 6 tyg. (maksimum 6 cykli).
Ciekawe ile razy i ile GBq 177Lu-PSMA-617 podają pacjentom w ośrodku Vivantes, tj. ile wlewwów obejmuje podstawowa cena 12 100 EUR.

[kemoturf]

Odpowiadając na wątpliwości, podawany koszt około 20k EUR raczej nie obejmuje całego leczenia. Trzeba by zapytać w konkretnym ośrodku.

W podanym niżej linku można przeczytać jak to wygląda w jednym z ośrodków w Berlinie (nie jest to wspomniany przez Zbyszko 55 Vivantes).
https://bookinghealth.com/helios-hospit ... -psma.html


Niestety tekst jest zabezpieczony przed kopiowaniem, więc podam tylko najważniejsze elementy, które obejmuje podana kwota 19 181 EUR:
- badanie laboratoryjne,
- USG ukladu moczowego,
- scyntygrafia nerek,
- PET PSMA przed zabiegiem, jeśli jest potrzebny
- 5 dniowy pobyt w szpitalu w pokoju dwuosobowym
- jeden wlew Lu177 - PSMA
- 2 scyntygrafie po zabiegu

Dalej w opisie pada zdanie, że potrzebne są 1-2 zabiegi przeprowdzone w odstępie 8 tygodni.
Na stronie innego ośrodka znalazłem informacje, że potrzebne są 3-4 zabiegi, zapewne wszystko zależy od odpowiedzi pacjenta na leczenie.


W Bunderwer Academic Hospital Berlin jest nieco taniej - 13 973 EUR.
Lekarzem głównym jest pani w stopniu doktora, a nie profesor.
Widzę taką prawidłowość, że tam gdzie nie profesor jest lekarzem głównym jest taniej.
Opis procedury praktycznie taki sam.

Pewnie trzeba napisać i zapytać o szczegóły.

[kemoturf]

W czerwcu 2021 opublikowano wyniki III fazy badania klinicznego z zastosowaniem PSMA-Lu177 (VISION).
Jak to określono, wyniki sa obiecujące... choć wg mnie słabo.


PSMA Targeted Therapy Trial Results: New Hope For Men With Prostate Cancer

The study results were positive. Patients treated with 177Lu-PSMA-617 were approximately 40% less likely to die and 60% less likely to have disease progression on scans vs. patients treated with standard of care alone.
Median overall survival was 15.3 months for patients in the 177Lu-PSMA-617 arm vs. 11.3 months in the standard of care alone arm.
Other measures in the trial also showed a significant benefit for 177Lu-PSMA-617.

https://www.pcf.org/blog/psma-targeted- ... te-cancer/

[leonardo556]

Ciekawe porównanie:

Lu-177-PSMA-617 vs Jevtana (cabazitaxel): which should I do next?
http://www.prostatecancer.news/2020/05/ ... taxel.html

[leonardo556]

Badania kliniczne z zastosowaniem 177 Lu-PSMA:

up.picr.de/42574912ge.png


Leonardo, Twój niemiecki anons dla szpiegów nie jest aktywny a 2 badania kliniczne z zastosowaniem 177Lu PSMA aktualnie rekrutujące pacjentów w PL są przedstawione w wątku BADANIA KLINICZNE PROWADZONE W POLSCE - patrz również mój post niżej. - zb

[zosia bluszcz]

Badania kliniczne z zastosowaniem 177Lu-PSMA:



1. Dla pacjentów z mHSPC


PSMAddition:

An Open-label, Randomised Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
NCT04720157




2. Dla pacjentów z mCRPC przed leczeniem Docetaxelem


PSMAfore:

A Phase III, Open-label, Multi-Center, Randomised Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer
NCT04689828



Bardziej szczegółowe kryteria włączenia do powyższych badań znajdziesz TUTAJ:

viewtopic.php?f=38&t=1940&p=120715#p120715

[Mieto]

Post przeniesiony z wątku Mieto:


Dla zainteresowanych kuracją lutetium-177 przesyłam garść informacji, jakie wyczytałem w niemieckiej prasie.

Na temat terapii lutetium-177 istniały tylko dwie publikacje, jedna z nich to:

177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study), "Journal of Nuclear Medicine and Molecular Imaging" (2021)
https://doi.org/10.1007/s00259-021-05525-7.


Ostatnio prof. dr Samer Ezziddin z kliniki medycyny nuklearnej w Saarbrücken podjął badania nad wykorzystaniem lutetium-177 bez specjalnego dobierania pacjentów pod kątem określonych kryteriów.
W jego badaniu wzięło udział 254 pacjentów, także ochotników, wielu miało niezbyt optymistyczne prognozy związane z przerzutami do wątroby i płuc. Kuracja trwa 2-3 tygodnie.
U ponad 50% pacjentów PSA spadło o więcej niż połowę, u ok. jednej trzeciej probantów pacjentów spadek był mniejszy niż 50%, co oznacza, że terapia Lutetem 177 przynajmniej zahamowała wzrost raka. Terapia Lutetem 177 powoduje niewielkie skutki uboczne.
Terapia ta może przedłużyć życie pacjentów o miesiące, czasem nawet o lata, bez pogorszania jakości życia.

Dla kogo przeznaczona jest terapia lutetium-177-PSMA:
- dla pacjentów z zaawansowanym, hormonoopornym rakiem,
- przy dobrym ogólnym stanie pacjenta,
- gdy zostały wyczerpane wszystkie inne możliwości leczenia

Terapia jest prowadzona przez zespól interdyscyplinarny.

Pacjent musi się dowiedzieć, czy jego kasa chorych przejmie koszty bardzo drogiej kuracji.

Obszerne studium w j. niemieckim dostępne jest pod adresem:
https://www.leitlinienprogramm-onkologi ... on_6.0.pdf

[zrebie]

Ciekawy wykład:


PSMA Scans & Pluvicto (lutetium-177) in 2022 | Geoffrey Johnson, MD, PhD | PCRI Conference 2022
https://www.youtube.com/watch?v=JoJomACA5UM

[zosia bluszcz]

W połowie grudnia 2022 EMA zatwierdziła wprowadzenie na rynek europejski Pluvicto® (177Lu PSMA).
Leczeniu w ramach terapii radioligandowej (RTL) z zastosowaniem preparatu Pluvicto mogą być poddawani pacjenci z wykazującym nadekspresję PSMA mCRPC, z progresją po uprzednim leczeniu ADT nowej generacji oraz CHT DX.

Nadekspresja PSMA musi być potwierdzona skanem PET/CT (lub PET/MR) 68Ga PSMA.



Novartis receives European Commission approval for Pluvicto® as the first targeted radioligand therapy for treatment of progressive PSMA–positive metastatic castration-resistant prostate cancer | Novartis

Basel, December 13, 2022 — Novartis today announced the European Commission (EC) approved Pluvicto® (INN: lutetium (177Lu) vipivotide tetraxetan), a targeted radioligand therapy.
Pluvicto® is approved in combination with androgen deprivation therapy (ADT) with or without androgen receptor (AR) pathway inhibition, for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC)3. These patients have been treated with AR pathway inhibition and taxane-based chemotherapy3.

The approval follows a positive opinion issued in October by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway, Northern Ireland and Liechtenstein.

The EC approval was granted based on results from the pivotal Phase III VISION trial, where participants, previously treated with AR pathway inhibition and taxane based chemotherapy, receiving Pluvicto® plus best standard of care (BSoC) had a 38% reduction in the risk of death and a statistically significant reduction (60%) in the risk of radiographic disease progression or death (rPFS) compared to BSoC alone1.
About a third (30%) of patients with evaluable disease at baseline demonstrated an objective response (per RECIST 1.1) with Pluvicto® plus BSoC, compared to the 2% in the BSoC-alone arm1.

https://www.novartis.com/news/media-rel ... ate-cancer



Scan for PSMA I PLUVICTO
https://www.hcp.novartis.com/products/p ... -for-psma/

pluvicto-epar-risk-management-plan_en.pdf

Pluvicto_ulotka leku.pdf

Na tym etapie trudno powiedzieć kiedy leczenie przy pomocy Pluvicto będzie dostępne w Polsce.
Koszt jednego zastrzyku Pluvicto w USA, to obecnie ok. 40 tys. USD.
W DE leczenie z zastosowaniem 177-Lu (ale nie gotowym preparatem Pluvicto), kosztowało ok. 20 tys. EUR za jedno podanie.


Leonardo w jednym ze swoich postów w wątku Kermita zasugerował Indie.
Szybka kwerenda i rzeczywiście - w jednym z miast satelitarnych New Delhi, Gurugram, znajduje się Fortis Memorial Research Institute z Nuclear Medicine Therapy Center, w którym oferowane jest leczenie z zastosowaniem 177Lu PSMA (nie Pluvicto).

Location of Nuclear Medicine Therapy Center in India
https://nuclearmedicinetherapy.in/locate-us


Koszt terapii - ok. 6 tys. USD za jedno podanie, wg informacji na stronie NMTC konieczne są 3-4 zastrzyki (maksimum 6) podawane co 8-12 tygodni (Pluvicto jest podawane co 6 tyg.).

Lowest Cost of Lu177 PSMA Therapy in India
https://nuclearmedicinetherapy.in/blog/ ... ma-therapy


Poniżej link do artykułów zamieszczonych na stronie nuclearmedecinetherapy.in :

Lutetium Lu177 PSMA Therapy for Prostate Cancer in India | Nuclear Medicine Therapy
https://nuclearmedicinetherapy.in/treat ... ma-therapy


Metastasis directed Lu-177 PSMA Therapy in Prostate Cancer Patients with Oligometastatic Disease
https://nuclearmedicinetherapy.in/blog/ ... ic-disease


Oraz linki do relacji z wyprawy do Fortis Memorial Research Institute/Nuclear Medicine Therapy Center jakoby autorstwa amerykańskiego pacjenta:

Medical Travel to India’s Fortis Memorial Research Institute – My Experience (Lu177 PSMA treatment)
https://nuclearmedicinetherapy.in/blog/ ... experience


My Experience Getting Lu177 PSMA Therapy In India at Fortis Memorial Research Institute (FMRI)
https://nuclearmedicinetherapy.in/blog/ ... itute-fmri


Pofatygowałam się również na Research Gate, gdzie wyguglałam poniższe:

Dr. Ishita SEN | Fortis Healthcare, New Delhi | Nuclear Medicine | Research profile
https://www.researchgate.net/profile/Ishita-Sen-3

Reasumując - wydaje się, że to indyjskie przedsięwzięcie ma ręce i nogi, ale caveat emptor!