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Medical Principles and Practice :... 2023Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an alpha emitter, is expected to have higher efficacy and fewer side effects compared to the beta-emitters such as Lutetium-177. We have performed a meta-analysis to assess the therapeutic responses, survival effects, and significant side effects of Ac-225 PSMA RLT in patients with mCRPC.
METHODOLOGY
Systematic literature search was carried out from five electronic databases PubMed/MEDLINE, SCOPUS, EMBASE, Web of Science, and Cochrane Library until March 2021. Eight studies were found to be eligible for this metanalysis.
RESULTS
Eight studies with 226 patients were analyzed in this metanalysis. 81% (95% CI 73-89) patients had a decline in PSA levels. 60% of the patients showed more than 50% PSA decline. Two studies assessed survival effects of radioligand naïve patients compared to patients who had received Lu-PSMA therapy previously and the pooled HR for radioligand naïve patients is 0.22. The most common toxicity reported was xerostomia in 167 patients out of 226 patients (73.9%, 95% CI 67.6-79.5%); however, most of them were confined to grade I and II levels. Other reported side effects include hematologic toxicity and nephrotoxicity.
CONCLUSION
Ac-PSMA RLT is a safe and potentially effective treatment option for patients with mCRPC.
Topics: Male; Humans; Actinium; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Prostate; Dipeptides; Treatment Outcome; Retrospective Studies
PubMed: 37247612
DOI: 10.1159/000531246 -
Frontiers in Oncology 2023Patients with hematological malignancies (HMs), like chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), have a high risk of...
Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review.
INTRODUCTION
Patients with hematological malignancies (HMs), like chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), have a high risk of secondary immunodeficiency (SID), SID-related infections, and mortality. Here, we report the results of a systematic literature review on the potential association of various cancer regimens with infection rates, neutropenia, lymphocytopenia, or hypogammaglobulinemia, indicative of SID.
METHODS
A systematic literature search was performed in 03/2022 using PubMed to search for clinical trials that mentioned in the title and/or abstract selected cancer (CLL, MM, or NHL) treatments covering 12 classes of drugs, including B-lineage monoclonal antibodies, CAR T therapies, proteasome inhibitors, kinase inhibitors, immunomodulators, antimetabolites, anti-tumor antibiotics, alkylating agents, Bcl-2 antagonists, histone deacetylase inhibitors, vinca alkaloids, and selective inhibitors of nuclear export. To be included, a publication had to report at least one of the following: percentages of patients with any grade and/or grade ≥3 infections, any grade and/or grade ≥3 neutropenia, or hypogammaglobulinemia. From the relevant publications, the percentages of patients with lymphocytopenia and specific types of infection (fungal, viral, bacterial, respiratory [upper or lower respiratory tract], bronchitis, pneumonia, urinary tract infection, skin, gastrointestinal, and sepsis) were collected.
RESULTS
Of 89 relevant studies, 17, 38, and 34 included patients with CLL, MM, and NHL, respectively. In CLL, MM, and NHL, any grade infections were seen in 51.3%, 35.9% and 31.1% of patients, and any grade neutropenia in 36.3%, 36.4%, and 35.4% of patients, respectively. The highest proportion of patients with grade ≥3 infections across classes of drugs were: 41.0% in patients with MM treated with a B-lineage monoclonal antibody combination; and 29.9% and 38.0% of patients with CLL and NHL treated with a kinase inhibitor combination, respectively. In the limited studies, the mean percentage of patients with lymphocytopenia was 1.9%, 11.9%, and 38.6% in CLL, MM, and NHL, respectively. Two studies reported the proportion of patients with hypogammaglobulinemia: 0-15.3% in CLL and 5.9% in NHL (no studies reported hypogammaglobulinemia in MM).
CONCLUSION
This review highlights cancer treatments contributing to infections and neutropenia, potentially related to SID, and shows underreporting of hypogammaglobulinemia and lymphocytopenia before and during HM therapies.
PubMed: 36824125
DOI: 10.3389/fonc.2023.1098326 -
Prostate Cancer and Prostatic Diseases Sep 2021Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen ligands (Ac-PSMA) has emerged as a promising treatment modality in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen ligands (Ac-PSMA) has emerged as a promising treatment modality in the management of metastatic castration-resistant prostate cancer (mCRPC). With its high linear energy transfer and short path length, Ac induces double-stranded DNA breaks and is expected to have excellent efficacy and safety profile. This systematic review was conducted to precisely evaluate the role of Ac-PSMA radioligand therapy (RLT) in mCRPC.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Searches were made using relevant keywords in the PubMed, Embase, and Scopus databases, and articles up to December 2020 were included. Data on efficacy and toxicity were extracted from the individual articles. Random-effects model was used for generating pooled estimates through meta-analysis.
RESULTS
Ten articles comprising 256 patients were included. Overall, 62.8% (95% confidence interval, CI: 53.4-71.7%) of the patients treated with Ac-PSMA RLT achieved biochemical response, i.e., ≥50% decline in the serum prostate-specific antigen levels from baseline. Molecular response on Gallium-68 PSMA positron emission tomography/computed tomography was noted in 74% (95% CI: 50.1-92.1%) of the patients. The pooled estimates of median progression-free survival and overall survival were 9.1 months (95% CI: 3.6-14.5 months) and 12.8 months (95% CI: 4.5-21.0 months), respectively. The most commonly reported adverse event was xerostomia, which was observed in 72.7% (95% CI: 50.5-90.1%) of the patients. However, clinically significant toxicity was limited with grade ≥3 xerostomia, anemia, leucopenia, thrombocytopenia, and nephrotoxicity occurring in 1.2%, 12.3%, 8.3%, 6.3%, and 3.8% of the patients, respectively. Treatment discontinuation due to adverse events was noted in 20/208 patients.
CONCLUSIONS
Ac-PSMA RLT is an efficacious and safe treatment option for patients with mCRPC. Future randomized controlled trials are required to establish its therapeutic efficacy and survival benefit vis-à-vis other approved treatment modalities.
Topics: Actinium; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Survival Rate
PubMed: 33746213
DOI: 10.1038/s41391-021-00349-w -
Biomolecules Aug 2023Following previously published systematic reviews on the diagnostic use of nanoparticles (NPs), in this manuscript, we report published methods for radiolabeling... (Review)
Review
Following previously published systematic reviews on the diagnostic use of nanoparticles (NPs), in this manuscript, we report published methods for radiolabeling nanoparticles with therapeutic alpha-emitting, beta-emitting, or Auger's electron-emitting isotopes. After analyzing 234 papers, we found that different methods were used with the same isotope and the same type of nanoparticle. The most common type of nanoparticles used are the PLGA and PAMAM nanoparticles, and the most commonly used therapeutic isotope is Lu. Regarding labeling methods, the direct encapsulation of the isotope resulted in the most reliable and reproducible technique. Radiolabeled nanoparticles show promising results in metastatic breast and lung cancer, although this field of research needs more clinical studies, mainly on the comparison of nanoparticles with chemotherapy.
Topics: Dendrimers; Isotope Labeling; Nanomedicine; Nanoparticles; Radioisotopes
PubMed: 37627307
DOI: 10.3390/biom13081241 -
The Prostate Jun 2021The aim of this systematic review and meta-analysis was to present an overview of the role of Ac-PSMA (prostate-specific membrane antigen)-targeted alpha therapy (TAT)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this systematic review and meta-analysis was to present an overview of the role of Ac-PSMA (prostate-specific membrane antigen)-targeted alpha therapy (TAT) as a salvage treatment option in metastatic castration-resistant prostate cancer.
METHODS
A systematic literature review was performed in databases such as Medline, Embase, PubMed, Cochrane Central Register of Controlled Clinical Trials, and the website; www.ClinicalTrials.gov until December 2020. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. All original articles, including retrospective, prospective, hand-searched articles, and clinical trials, were searched, and appropriate data were included for the analysis. The study's primary endpoint assessed therapeutic efficacy by biochemical response assessment criteria (any prostate-specific antigen [PSA] decline and >50% PSA decline from the baseline) after Ac-PSMA-TAT. The secondary endpoints included assessing overall survival (OS), progression-free survival (PFS), molecular response, and therapy-related adverse events across all the studies. The values were expressed as pooled proportions and demonstrated graphically by forest plots using the random-effects model.
RESULTS
After the data extraction and filtration process, a total of three publications, including 141 patients, were included for the final analysis. The pooled proportion of patients demonstrating any PSA decline and greater than 50% PSA decline were 83% (95% confidence interval [CI]: 77%-89%) and 59% (95% CI: 42%-76%), respectively. The pooled proportions for OS was 81% (95% CI: 74%-89%). The pooled proportion of patients who have shown complete molecular response are 17% (95% CI: 5%-29%). The median PFS was 12 months (interquartile range: 8.2-14.4 months). Across the studies, the most common side effects from Ac-PSMA-617 TAT were xerostomia/dry mouth, which pertained to Gr I-II in 63.1% (89 of 141), followed by fatigue in 44.5% (45 of 101) of patients. Grade I-II and III anemia was noted in 48.5% (49 of 101) and 6% (6 of 101), respectively. Grade III leukopenia and thrombocytopenia were negligible: 0.9% (1 of 101) and 0.9% (1 of 101), respectively. Similarly, grade III nephrotoxicity was also observed only in 5 of 101 (5%) patients.
CONCLUSION
Treatment with Ac-PSMA-617 TAT demonstrated biochemical response, improved survival, caused low treatment-related toxicity proving a promising salvage treatment option in mCRPC patients.
Topics: Actinium; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Theranostic Nanomedicine; Treatment Outcome
PubMed: 33905559
DOI: 10.1002/pros.24137 -
World Journal of Nuclear Medicine 2021Neuroendocrine neoplasms (NENs) are a very diverse group of tumors with a worldwide rise in incidence. Systemic therapy remains the mainstay treatment for unresectable... (Review)
Review
Neuroendocrine neoplasms (NENs) are a very diverse group of tumors with a worldwide rise in incidence. Systemic therapy remains the mainstay treatment for unresectable and/or metastatic NENs. Lu-DOTATATE, a radiopharmaceutical which emits beta particles, has emerged as a promising therapy for metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, limited treatment options are available particularly after the failure of Lu-DOTATATE therapy. This review aims to identify and summarize the available evidence for, and potential adverse events of, targeted alpha-particle therapy (TAT) in the treatment of metastatic NENs, specifically GEP-NENs. The MEDLINE, EMBASE, SCOPUS, and Cochrane Library databases were searched. Two articles which met the inclusion criteria were identified and included in the review. Putative radiopharmaceuticals that can be considered for metastatic NEN treatment include Actinium (Ac)-DOTATATE and Bismuth (Bi)-DOTATOC. There was evidence of partial response using both radiopharmaceutical agents without significant hematological, renal, or hepatotoxicity. Future studies should consider longer term, randomized controlled trials investigating the role of TAT, in particular, Ac-DOTATATE, in the treatment of metastatic NENs.
PubMed: 35018146
DOI: 10.4103/wjnm.wjnm_160_20 -
The Prostate Jul 2023Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen agents (225Ac-PSMA) is currently being studied in clinical trials for patients... (Review)
Review
BACKGROUND
Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen agents (225Ac-PSMA) is currently being studied in clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC). Compared to β-emitting therapeutic radionuclides, alpha-emitters (e.g., 225Ac) have a significantly higher linear energy transfer and significantly shorter range. As a result, alpha emitters could be expected to improve efficacy and reduce bystander toxicity. This systematic literature review was conducted to evaluate the impact of sequencing of 177Lu-PSMA and 225Ac-PSMA targeted radionuclide therapy (TRT) in mCRPC.
METHODS
The present systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The searches were made using relevant keywords in the PubMed, Scopus, and Web of Science databases, and articles up to August 22, 2022, were included. Publications were excluded if they were duplicate publications, wrong study or publication format, or discussing a topic out of scope. Data on efficacy, toxicity, and health-related quality of life were extracted from the individual articles. The I index was used to measure the extent of heterogeneity amongst studies. In the studies that reported subgroup outcomes according to the prior status on 177Lu-PSMA TRT, pooled estimates of the main outcomes were generated through descriptive analysis. Quality assessment was performed using the Newark-Ottawa-scale.
RESULTS
The study included 12 articles; 1 series was performed prospectively. In total, data of 329 patients were analyzed. About 40.1% (n = 132) of the included men were pretreated with 177Lu-PSMA TRT. Seven studies, including data of 212 individuals, were eligible for quantitative analysis based on reporting outcomes of the subgroups according to their prior status on 177Lu-PSMA TRT. >25% PSA decline after 225Ac-PSMA TRT was lower in individuals who received prior 177Lu-PSMA TRT (pooled median 42.7%) compared to those who did not (pooled median 15.4%). The pooled medians of the reported median progression-free survival and overall survival for pretreated versus not pretreated individuals was 4.3 versus 14.3 months and 11.1 versus 9.2 months, respectively. However, the outcomes for each individual study were reported inconsistently (I = 99.9%). None of the included studies stratified the report of adverse events or changes in health-related quality of life for the subgroups.
CONCLUSIONS
225Ac-PSMA TRT is an experimental treatment for men with mCRPC. There is limited data available from high-quality trials but so far PSMA-targeted TRT has demonstrated a low morbidity profile. Our review revealed that there is a possible decrease in efficacy of targeted alpha-particle therapy if individuals previously were exposed to 177Lu-PSMA TRT. However, the level of evidence is low. The underlying mechanism by which 177Lu-PSMA TRT might trigger possible radioresistance as well as randomized controlled trials are required to establish the therapeutic efficacy and safety of 225-Ac-PSMA TRT in men refractory to 177Lu-PSMA TRT.
Topics: Male; Humans; Actinium; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Prostate-Specific Antigen; Treatment Outcome; Radioisotopes
PubMed: 36960580
DOI: 10.1002/pros.24531 -
EJNMMI Research Feb 2021Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. While most of the... (Review)
Review
PURPOSE
Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. While most of the existing literature has been focussed on the application of FAP-specific PET in various kinds of cancers, some researchers have, both intentionally or unintentionally, used FAP-specific PET in patients with non-cancerous diseases. The purpose of this systematic review is therefore to summarize the available evidence of FAP-specific PET for non-malignant indications.
METHODS
The MEDLINE database was searched for studies presenting the clinical use of FAP-specific PET, the records were screened according to PRISMA guidelines and articles containing patients suffering from non-malignant diseases were included.
RESULTS
Sixteen studies with 303 patients were included. FAP-specific PET has been used in cardiac imaging, IgG-related disease, benign tumors as well as various kinds of inflammation. Two prospective studies on FAP-specific PET for IgG-related disease show its potential to differentiate inflammatory from fibrotic lesions, which could be used to determine the management of these patients.
CONCLUSION
While publications on FAP-specific PET for non-malignant indications are mostly limited to case reports and incidental findings, the first retrospective and prospective studies present promising results for IgG-related as well as cardiovascular disease that warrant further research. Several currently recruiting trials will add to the body evidence in the next few years.
PubMed: 33606104
DOI: 10.1186/s13550-021-00761-2 -
European Journal of Nuclear Medicine... Jan 2020To summarise data with radium-223 dichloride (RaCl), a mechanism-mediated targeted alpha therapy (TAT), in metastatic castration-resistant prostate cancer (mCRPC) and to...
PURPOSE
To summarise data with radium-223 dichloride (RaCl), a mechanism-mediated targeted alpha therapy (TAT), in metastatic castration-resistant prostate cancer (mCRPC) and to chart the development of TAT in mCRPC and in other tumour types.
METHODS
Literature for this systematic review was identified using a PubMed search: ("targeted alpha therapy" or "targeted alpha particle therapy") or (213-bismuth or bismuth-213 or 213Bi) or (225-actinium or actinium-225 or 225Ac) or (211-astatine or astatine-211 or 211At) or (212-lead or lead-212 or 212Pb) or (227-thorium or thorium-227 or 227Th) or (223-radium or radium-223 or 223Ra or alpharadin) and (malignancy or cancer). Results were limited to English-language publications in humans, with the article type "clinical trial".
RESULTS
Forty-one publications were included (30 from the literature search and 11 from manual searches/reviews). In clinical trials in mCRPC, RaCl monotherapy is well tolerated, with significantly longer overall survival than placebo and improved quality of life. Clinical trial data have been reinforced by findings from real-world studies. RaCl has also shown promise in other tumour types with bone metastases, including advanced breast cancer and advanced renal cell carcinoma (in combination with anti-vascular endothelial growth factor). Several astatine-211- and bismuth-213-labelled molecules have demonstrated anti-tumour activity and acceptable toxicity in other tumour types.
CONCLUSIONS
RaCl has demonstrated "proof of concept" for use of TAT in cancer in clinical practice. The efficacy and safety of RaCl monotherapy have been demonstrated in mCRPC, and RaCl combination therapies are under investigation in various tumours. TAT has broad applicability across tumour types.
Topics: Actinium; Astatine; Bismuth; Bone Neoplasms; Humans; Lead Radioisotopes; Male; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Radioisotopes; Radium; Thorium
PubMed: 31471713
DOI: 10.1007/s00259-019-04475-5