Stefano Severi1, Maddalena Sansovini2, Annarita Ianniello2, Lisa Bodei3, Silvia Nicolini2, Toni Ibrahim4, Valentina Di Iorio5, Vincenzo D'Errico6, Paola Caroli2, Manuela Monti7, Giovanni Paganelli2. 1. Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy. stefano.severi@irst.emr.it. 2. Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, FC, Italy. 3. Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy. 4. Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Oncology Pharmacy Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 7. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Abstract
PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with (177)Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with (90)Y-DOTATOC (Y-PRRT). METHODS: Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. RESULTS: Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6%, median PFS was 22 months (95% CI 16 months - not reached) compared to 28 months (95% CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. CONCLUSION: Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment.
PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with (177)Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with (90)Y-DOTATOC (Y-PRRT). METHODS: Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. RESULTS: Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6%, median PFS was 22 months (95% CI 16 months - not reached) compared to 28 months (95% CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. CONCLUSION:Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment.
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Authors: L Bodei; M Kidd; I M Modlin; S Severi; I Drozdov; S Nicolini; D J Kwekkeboom; E P Krenning; R P Baum; G Paganelli Journal: Eur J Nucl Med Mol Imaging Date: 2015-11-23 Impact factor: 9.236
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