Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients
Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (<sup>177</sup>Lu-PSMA RLT) is an effective salvage treatment. However, studies have high...
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MDPI AG
2021-03-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/11/3/515 |
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| author | Murali Kesavan Danielle Meyrick Marat Gallyamov J. Harvey Turner Sharon Yeo Giuseppe Cardaci Nat P. Lenzo |
| author_facet | Murali Kesavan Danielle Meyrick Marat Gallyamov J. Harvey Turner Sharon Yeo Giuseppe Cardaci Nat P. Lenzo |
| author_sort | Murali Kesavan |
| collection | DOAJ |
| description | Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (<sup>177</sup>Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative <sup>177</sup>Lu-DOTAGA-(I-y)fk(Sub-KuE) (<sup>177</sup>Lu-PSMA I&T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (<sup>68</sup>Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of <sup>177</sup>Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (<i>p</i> < 0.0001; 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: <sup>177</sup>Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. <sup>68</sup>Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy. |
| first_indexed | 2024-03-10T13:15:07Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T13:15:07Z |
| publishDate | 2021-03-01 |
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| series | Diagnostics |
| spelling | doaj.art-0ba78a99ed934bc7923b5dcbd518f7312023-11-21T10:27:50ZengMDPI AGDiagnostics2075-44182021-03-0111351510.3390/diagnostics11030515Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated PatientsMurali Kesavan0Danielle Meyrick1Marat Gallyamov2J. Harvey Turner3Sharon Yeo4Giuseppe Cardaci5Nat P. Lenzo6Department of Haematology, School of Medicine, The University of Western Australia, Perth 6009, AustraliaDepartment of Nuclear Medicine, School of Medicine, The University of Western Australia, Perth 6009, AustraliaGenesisCare, East Fremantle, Fremantle 6158, AustraliaDepartment of Nuclear Medicine, School of Medicine, The University of Western Australia, Perth 6009, AustraliaGenesisCare, East Fremantle, Fremantle 6158, AustraliaSchool of Medicine, The University of Notre Dame, Fremantle 6160, AustraliaGenesisCare, East Fremantle, Fremantle 6158, AustraliaBackground: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (<sup>177</sup>Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative <sup>177</sup>Lu-DOTAGA-(I-y)fk(Sub-KuE) (<sup>177</sup>Lu-PSMA I&T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (<sup>68</sup>Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of <sup>177</sup>Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (<i>p</i> < 0.0001; 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: <sup>177</sup>Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. <sup>68</sup>Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.https://www.mdpi.com/2075-4418/11/3/515LuPSMAmCRPChematologic toxicityMDS |
| spellingShingle | Murali Kesavan Danielle Meyrick Marat Gallyamov J. Harvey Turner Sharon Yeo Giuseppe Cardaci Nat P. Lenzo Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients Diagnostics LuPSMA mCRPC hematologic toxicity MDS |
| title | Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients |
| title_full | Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients |
| title_fullStr | Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients |
| title_full_unstemmed | Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients |
| title_short | Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients |
| title_sort | efficacy and haematologic toxicity of palliative radioligand therapy of metastatic castrate resistant prostate cancer with lutetium 177 labeled prostate specific membrane antigen in heavily pre treated patients |
| topic | LuPSMA mCRPC hematologic toxicity MDS |
| url | https://www.mdpi.com/2075-4418/11/3/515 |
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