Early side effects and first results of radioligand therapy with 177Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study

Abstract

BackgroundRadioligand therapy (RLT) with 177Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments.MethodsRLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). 68Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5–853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1–6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes.ResultsEight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4).ConclusionsOur initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

“…Standard administered activity of 177 Lu PSMA has been variable across the currently published literature as institutions undertake safety and toxicity trials 3, 5, 7, 8, 20, 21, 24, 25, 26, 27, 28, 29. Injected doses have ranged from 3 to 8 GBq per single injections with up to six injections given to men, generally at a minimum 6‐weekly intervals.…”

Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

“…Simultaneously, the PSA response rates are lower in comparison to the older 131 I-PSMA-RLT data exploiting the full 1 Gy red-marrow tolerance limit (10,16). Surprisingly, none of the authors (22)(23)(24)(25)(26)(27)(28) discussed the possibility that escalation of 177 Lu treatment activity to an estimated redmarrow absorbed dose between 0.2-1.0 Gy should still be well tolerable but offers the chance to further improve anti-tumor-activity because a positive dose/responserelationship is normally expected in radiotherapy. Therefore, after clinical introduction of 177 Lu-PSMA-617, for us it seemed ethical mandatory to increase treatment activity until either non-dramatically grade-1/2 toxicities appear or patients achieve enduring remissions.…”

German Multicenter Study Investigating177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

“…Since 2015, several studies reported promising results for response rates and a favorable safety profile after radioligand therapy (RLT) with 177 Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) (12)(13)(14)(15)(16). In a single-center study of 28 patients, a slight improvement of survival compared with a matched group of best supportive-care patients (historical population) was demonstrated (16).…”