Lutetium-177 (Lutathera, Lu-Dotatate)

Lu 177 dotatate is the first FDA-approved peptide receptor radionuclide therapy.

Tradename Pluvicto.

Lu-PSMA-617 delivers beta-particle radiation selectively to PSMA positive cells and the surrounding micro environment.

Lutetium177 is indicated for the treatment of adult patients with prostate specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.

It is an ad-on injection therapy for patients with prostate specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer who have previously been treated with the androgen receptor pathway inhibition and taxane based chemotherapy.

Approved lutetium Lu 177 dotatate (Lutathera) for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults.

Lutetium Lu 177 dotatate is a radiolabeled somatostatin analog.

It is a form of targeted treatment comprising a targeting molecule that carries a radioactive component.

The approval included tumors of the foregut, midgut, and hindgut.

NETTER-1 trial, which included 229 patients with progressive, well-differentiated, locally advanced, inoperable, or metastatic somatostatin receptor positive midgut carcinoid tumors randomly assigned to lutetium Lu 177 dotatate every 8 weeks for up to 4 administrations plus long-acting octreotide, or the standard of care: high-dose long-acting octreotide.

The median progression-free survival was not yet reached in patients assigned lutetium Lu 177 dotatate compared with 8.5 months in the high-dose long-acting octreotide group.

Significantly delays time to deterioration in the quality of life in patients with progressive midgut neuroendocrine tumors.

This translated into a 79% reduction in the risk of disease progression or death.

Interim analysis of overall survival that showed a 48% reduction in the risk of death with lutetium Lu 177 dotatate compared with standard of care.

The objective response rate with lutetium Lu 177 dotatate was 13% compared with 4% for high-dose long-acting octreotide.

The most common adverse events in the intervention arm of NETTER-1 were lymphopenia, increased gamma-glutamyltransferase, vomiting, nausea, and elevated AST.

It can cause severe and life-threatening myelosuppression, and also renal toxicity.

In addition, with a median follow-up of 2 years, 2.7% of patients in the lutetium Lu 177 dotatate arm developed myelodysplastic syndromes compared with no patients in the comparison arm.

The efficacy of lutetium Lu 177 dotatate was also evaluated in a subset of 360 patients enrolled in a study of GEP-NET tumors at the Erasmus Medical Center in the Netherlands: patients had an overall response rate of 16%, including three complete responses.

Radilogand therapy Lu-PSMA-617 prolonged the increased progression free survival in overall survival when added to standard care in patients with advanced  PSMA positive metastatic castration resistant prostate cancer (Vision Investigators).

VISION trial utilized radioligand therapy with lutetium 177 prostate specific membrane antigen 617 invitation to standard therapy for heavily treating patients with progressive disease: median overall survival significantly longer in the trial group than  in the control group of 15.3 versus 11.3 months respectively.

In the VISION  trial median radiographic progression free survival was also significantly longer than the control group of 8.7 versus 3.4 months, respectively.

The rate of declining PSA, objective response rate, median time to first symptomatic skeletal event was also increased in the LU-PSMA-617 trial.

In the VISION trial adverse events including bone marrow suppression, anemia, thrombocytopenia, which were more common in this heavily treated group.

The therapy is delivered by injection every six weeks for up to six doses.

Patients receiving standard care plus luteum LU 177 vipivotude tetraxetan had significant reduction in the risk of death with the median overall survival of 15.3 months compared with 11.3 months for the standard of care only control group in metastatic Prostate cancer.

It is given every eight weeks for four treatments.

Relative in contraindications include GFR less than 30 and the presence of liver disease.

adverse effects include: myelosuppression, nephrotoxicity, Pero, toxicity, nausea and vomiting, carcinoid crisis, fetal toxicity, infertility, and rarely the development of myelodysplastic syndrome or leukemia.

It is  usually administered with an amino acid infusion, usually arginine and lysine to provide natural protection.

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