Salvage Radiopeptide Therapy of Advanced Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen: Efficacy and Safety in Routine Practice

Cancer Biother Radiopharm. 2018 Sep;33(7):274-281. doi: 10.1089/cbr.2017.2403. Epub 2018 Jul 10.

Abstract

Background: Prostate-specific membrane antigen (PSMA)-based radiopeptide/radioligand therapy represents a rapidly expanding field in the management of metastatic castrate-resistant prostate cancer (mCRPC). However, there remains concern for the development of significant toxicities in heavily pretreated patients. In this study, the authors present their local experience, with respect to efficacy and toxicity, of 22 consecutive patients treated with lutetium-177-DOTAGA-(I-y)fk(Sub-KuE) or 177Lu-PSMA I&T radioimmunotherapy for progressive mCRPC, followed up over 1 year.

Materials and methods: All patients had progressive mCRPC, an European Cooperative Oncology Group (ECOG) ≤2 with adequate bone marrow and liver function. 177Lu-PSMA I&T therapy was administered at 8-week intervals with a mean prescribed activity of 5.5 GBq (gigabecquerel) per patient.

Results: Twenty patients had evaluable results, median age of 71 years, and median duration of follow-up of 17 months. Three patients (15%) experienced a G1/2 myelotoxicity and four (20%) G3/4. No incidences of myelodysplasia/acute leukemia have been identified. All toxicities were self-limiting. Baseline cytopenia was predictive of the development of subsequent G3/4 myelotoxicity (p = 0.0035). Eight patients (40%) experienced an objective PSA response, with a median time to response of 15 weeks. The median time to PSA progression was not reached. Patients receiving three cycles of therapy were statistically more likely to experience a disease response when compared to those treated with one, two, or four cycles (p < 0.0001).

Conclusions: 177Lu-PSMA I&T radioimmunotherapy of progressive mCRPC is safe and effective with three cycles being the potential optimal number for determining long-term disease response.

Keywords: bone marrow; bone metastases; lutetium; metastasis; prostate cancer; response to treatment.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Surface / chemistry
  • Antigens, Surface / immunology
  • Antigens, Surface / therapeutic use*
  • Glutamate Carboxypeptidase II / chemistry
  • Glutamate Carboxypeptidase II / immunology
  • Glutamate Carboxypeptidase II / therapeutic use*
  • Humans
  • Kallikreins / blood
  • Lutetium / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prostate
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radioimmunotherapy / adverse effects
  • Radioimmunotherapy / methods*
  • Radioisotopes / therapeutic use
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / therapeutic use*
  • Retrospective Studies
  • Salvage Therapy / adverse effects
  • Salvage Therapy / methods*
  • Treatment Outcome

Substances

  • Antigens, Surface
  • Radioisotopes
  • Radiopharmaceuticals
  • Lutetium
  • Lutetium-177
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen