Efficacy and safety of 177Lutetium-prostate-specific membrane antigen therapy in metastatic castration-resistant prostate cancer patients: First experience in West Asia – A prospective study

Aghdam, Ramin Akbarian; Amoui, Mahasti; Ghodsirad, Mohammadali; Khoshbakht, Sepide; Mofid, Bahram; Kaghazchi, Fateme; Tavakoli, Mehrdad; Pirayesh, Elahe; Ahmadzadehfar, Hojjat

doi:10.4103/wjnm.wjnm_66_18

“…The salient features of reviewed studies are summarized in Table 1. With regard to predictors of response to therapy and overall survival, numerous studies have shown that patients with PSA decline in response to RLT experience longer overall survival compared to those who do not respond [12,[17][18][19][20][21][22][23][24][25]. It also appears that the degree of PSA decline correlates with the outcome.…”

Section: Reviewmentioning

confidence: 99%

“…A minority of patients had high-grade hematological toxicities that were dose-dependent. Typically, platelets nadir around four weeks after therapy, while the leukocyte count nadirs around two weeks after therapy [18,25]. Cytopenias are generally transient, with counts eventually returning to normal ranges.…”

Section: Reviewmentioning

confidence: 99%

“…Cytopenias are generally transient, with counts eventually returning to normal ranges. Less serious, but more common, side effects included xerostomia, fatigue, and nausea [14,25]. Conclusions 177 Lu-PSMA-617 RLT has emerged as a viable and effective therapy in patients with progressive metastatic prostate cancer, with a majority of patients responding to the therapy.…”

Section: Reviewmentioning

confidence: 99%

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Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

Sun¹,

Niaz²,

Nelson³

et al. 2020

Cureus

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Prostate-specific membrane antigen (PSMA) is a cell membrane glycoprotein that is selectively expressed in prostate cells, with expression levels increasing dramatically in prostatic adenocarcinoma. PSMA-based radioligand therapy (RLT) has emerged as a viable therapeutic modality for the treatment of progressive metastatic prostate cancer. One commonly employed combination involves lutetium-177 conjugated to the ligand PSMA-617 (177 Lu-PSMA-617). In this meta-analysis, we examine therapeutic responses in patients with metastatic disease who have received 177 Lu-PSMA-617 therapy. We conducted a literature search with the following inclusion criteria: clinical trials involving more than 10 patients and solely utilizing 177 Lu-PSMA-617. Seventeen studies were included in the final analysis. Variables documented included the number of patients, the total therapeutic dose administered, the percentage of any prostate-specific antigen (PSA) decline, the percentage with PSA decline exceeding 50% baseline, and toxicities. Overall, a majority of patients responded to therapy, and in the prospective studies, survival was found to be upwards of one year. Significant toxicities included cytopenias, which were infrequent. Patients who had PSA declines in response to therapy had longer survival. Performance status and tumor grade were also key predictors of outcome.

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“…PSMA-targeted RPT has provided a new alternative to managing patients with advanced PC refractory to other therapies 54 , 55 . Recent prospective trials of 177 Lu-based therapies have demonstrated substantial imaging and PSA responses 56 , 57 . Fewer side effects than other systemic therapies, such as hormonal or chemotherapy, have repeatedly been shown 58 .…”

Section: Discussionmentioning

confidence: 99%

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

Boinapally

¹

,

Ahn

²

,

Cheng

³

et al. 2021

Sci Rep

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Prostate-specific membrane antigen (PSMA) is a promising target for the treatment of advanced prostate cancer (PC) and various solid tumors. Although PSMA-targeted radiopharmaceutical therapy (RPT) has enabled significant imaging and prostate-specific antigen (PSA) responses, accumulating clinical data are beginning to reveal certain limitations, including a subgroup of non-responders, relapse, radiation-induced toxicity, and the need for specialized facilities for its administration. To date non-radioactive attempts to leverage PSMA to treat PC with antibodies, nanomedicines or cell-based therapies have met with modest success. We developed a non-radioactive prodrug, SBPD-1, composed of a small-molecule PSMA-targeting moiety, a cancer-selective cleavable linker, and the microtubule inhibitor monomethyl auristatin E (MMAE). SBPD-1 demonstrated high binding affinity to PSMA (Ki = 8.84 nM) and selective cytotoxicity to PSMA-expressing PC cell lines (IC50 = 3.90 nM). SBPD-1 demonstrated a significant survival benefit in two murine models of human PC relative to controls. The highest dose tested did not induce toxicity in immunocompetent mice. The high specific targeting ability of SBPD-1 to PSMA-expressing tumors and its favorable toxicity profile warrant its further development.

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“…PSMA-targeted RPT has provided a new alternative to managing patients with advanced PC refractory to other therapies 54,55 . Recent prospective trials of 177 Lu-based therapies have demonstrated substantial imaging and PSA responses 56,57 . Fewer side effects than other systemic therapies, such as hormonal or chemotherapy, have repeatedly been shown 58 .…”

Section: Discussionmentioning

confidence: 99%

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

Srikanth

¹

,

Ahn

²

,

Cheng

³

et al. 2020

Preprint

0

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Prostate-specific membrane antigen (PSMA) is a promising target for the treatment of advanced prostate cancer (PC) and various solid tumors. Although PSMA-targeted radiopharmaceutical therapy (RPT) has enabled significant imaging and prostate-specific antigen (PSA) responses, accumulating clinical data are beginning to reveal certain limitations, including a subgroup of non-responders, relapse, radiation-induced toxicity, and the need for specialized facilities for its administration. To date non-radioactive attempts to leverage PSMA to treat PC with antibodies, nanomedicines or cell-based therapies have met with modest success. We developed a non-radioactive prodrug, SBPD-1, composed of a small-molecule PSMA-targeting moiety, a cancer-selective cleavable linker, and the microtubule inhibitor monomethyl auristatin E (MMAE). SBPD-1 demonstrated high binding affinity to PSMA (Ki = 8.84 nM) and selective cytotoxicity to PSMA-expressing PC cell lines (IC50 = 3.90 nM). SBPD-1 demonstrated a significant survival benefit in two murine models of human PC relative to controls. The highest dose tested did not induce toxicity in immunocompetent mice. The high specific targeting ability of SBPD-1 to PSMA-expressing tumors and its favorable toxicity profile warrant its further development.

show abstract

Efficacy and safety of 177Lutetium-prostate-specific membrane antigen therapy in metastatic castration-resistant prostate cancer patients: First experience in West Asia – A prospective study

Cited by 23 publications

References 31 publications

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

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