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Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer
Abstract
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly being used in metastatic castration-resistant prostate cancer (mCRPC). The objective of this study is to report our clinical experience with RLT using 177-lutetium-labeled PSMA-I&T. A total of 100 patients were treated under a compassionate use protocol with a total number of 319 cycles (median two cycles, range 1-6). Eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or chemoineligibility, and positive PSMA-ligand uptake at positron-emission tomography scan. The 177Lu-PSMA-I&T was given 6-8 weekly with an activity of 7.4 GBq up to six cycles. The median number of previous mCRPC regimens was 3 (range 1-6), and 35 patients had visceral metastases. Prostate-specific antigen decline of ≥50% was achieved in 38 patients, median clinical progression-free survival (cPFS) was 4.1mo, and median overall survival (OS) was 12.9mo. Subgroup analyses identified an association of visceral metastases with a poor prostate-specific antigen (PSA) response and shorter cPFS and OS, and an association of rising lactate dehydrogenase (LDH) with shorter cPFS and OS. Patients achieving PSA decline of ≥50% within 12wk of treatment showed longer cPFS and OS. Treatment-emergent hematologic grade 3/4 toxicities were anemia (9%), thrombocytopenia (4%), and neutropenia (6%). Grade 3/4 nonhematologic toxicities were not observed. RLT with 177Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage mCRPC at low toxicity. Presence of visceral metastases and rising LDH were associated with worse treatment outcome. PATIENT SUMMARY: We analyzed the treatment outcome and toxicity of prostate-specific membrane antigen-targeted radioligand therapy in patients with metastatic castration-resistant prostate cancer. We found that a good treatment response could be achieved in a subgroup of patients with few side effects. We also observed that treatment outcome was worse in patients with organ metastases and elevated lactate dehydrogenase in blood tests.
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Hofman, M. S., Violet, J., Hicks, R. J., Ferdinandus, J., Thang, S. P., Akhurst, T., Iravani, A., Kong, G., Ravi Kumar, A., Murphy, D. G., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30198-0 · Cited by 1,174
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Maurer, T., Gschwend, J. E., Rauscher, I., Souvatzoglou, M., Haller, B., Weirich, G., Wester, H.-J., Heck, M., Kübler, H., Beer, A. J., et al. (2016) · Journal of Urology · doi:10.1016/j.juro.2015.12.025 · Cited by 779
Self-citationBaum, R. P., Kulkarni, H. R., Schuchardt, C., Singh, A., Wirtz, M., Wiessalla, S., Schottelius, M., Mueller, D., Klette, I., & Wester, H.-J. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.168443 · Cited by 525
Self-citationComparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer
Pyka, T., Okamoto, S., Dahlbender, M., Tauber, R., Retz, M., Heck, M., Tamaki, N., Schwaiger, M., Maurer, T., & Eiber, M. (2016) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-016-3435-0 · Cited by 370
Self-citationZechmann, C. M., Afshar-Oromieh, A., Armor, T., Stubbs, J. B., Mier, W., Hadaschik, B., Joyal, J., Kopka, K., Debus, J., Babich, J. W., et al. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-014-2713-y · Cited by 358
Delker, A., Fendler, W. P., Kratochwil, C., Brunegraf, A., Gosewisch, A., Gildehaus, F. J., Tritschler, S., Stief, C. G., Kopka, K., Haberkorn, U., et al. (2016) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-015-3174-7 · Cited by 322
Heck, M. M., Retz, M. M., D’Alessandria, C., Rauscher, I., Scheidhauer, K., Maurer, T., Storz, E., Janssen, F., Schottelius, M., Wester, H., et al. (2016) · The Journal of Urology · doi:10.1016/j.juro.2016.02.2969 · Cited by 187
Self-citationRahbar, K., Boegemann, M., Yordanova, A., Eveslage, M., Schäfers, M., Essler, M., & Ahmadzadehfar, H. (2018) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-017-3848-4 · Cited by 158
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Hofman, M. S., Emmett, L., Sandhu, S., Iravani, A., Joshua, A. M., Goh, J. C., Pattison, D. A., Tan, T. H., Kirkwood, I. D., Ng, S., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00237-3 · Cited by 1,170
Gafita, A., Calais, J., Grogan, T. R., Hadaschik, B., Wang, H., Weber, M., Sandhu, S., Kratochwil, C., Esfandiari, R., Tauber, R., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00274-6 · Cited by 271
Self-citationPeters, S. M. B., Privé, B. M., de Bakker, M., de Lange, F., Jentzen, W., Eek, A., Muselaers, C. H. J., Mehra, N., Witjes, J. A., Gotthardt, M., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05471-4 · Cited by 88
Iravani, A., Violet, J., Azad, A., & Hofman, M. S. (2020) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-019-0174-x · Cited by 68
Karimzadeh, A., Heck, M., Tauber, R., Solaris, E., Nekolla, S., Knorr, K., Haller, B., D’Alessandria, C., Weber, W. A., Eiber, M., et al. (2023) · Journal of Nuclear Medicine · doi:10.2967/jnumed.122.265346 · Cited by 19
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Metadata
- Authors
- Heck, M. M., Tauber, R., Schwaiger, S., Retz, M., D’Alessandria, C., Maurer, T., Gafita, A., Wester, H.-J., Gschwend, J. E., Weber, W. A., Schwaiger, M., Knorr, K., & Eiber, M.
- Venue
- European Urology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 75
- Issue
- 6
- Pages
- 920-926
- ISSN
- 0302-2838 (ISSN-L)
- OpenAlex
- W2900829249
- Cited by
- 298
- References
- 13
- FWCI
- 19.21
- Type
- journal article
- Language
- en
- Open access
- closed
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- Heck, M. M., Tauber, R., Schwaiger, S., Retz, M., D’Alessandria, C., Maurer, T., Gafita, A., Wester, H.-J., Gschwend, J. E., Weber, W. A., Schwaiger, M., Knorr, K., & Eiber, M. (2019). Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer. European Urology. https://doi.org/10.1016/j.eururo.2018.11.016
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