Efficacy and safety of 225Ac-DOTATATE targeted alpha therapy in metastatic paragangliomas: a pilot study

• Published in: European journal of nuclear medicine and molecular imaging 2022-04, Vol.49 (5), p.1595-1606
• Main Authors: Yadav, Madhav Prasad, Ballal, Sanjana, Sahoo, Ranjit Kumar, Bal, Chandrasekhar
• Format: Article
• Language: English
• Subjects: Analgesics; Antihypertensives; Cardiology; Criteria; Disease control; Health services; Imaging; Lutetium; Lutetium isotopes; Medical treatment; Medicine; Medicine & Public Health; Metastases; Neuroendocrine tumors; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Paraganglioma; Patients; Radiation therapy; Radioisotopes; Radiology; Safety; Theragnostic
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-021-05632-5

Purpose In this study, we aim to evaluate the efficacy and safety of 225 AC-DOTATATE targeted alpha therapy in advanced-stage paragangliomas (PGLs). Methods Nine (6 males and 3 females) consecutive patients with histologically proven PGLs were treated with 225 Ac-DOTATATE targeted alpha therapy (TAT) and concomitant radiosensitizer, capecitabine, at 8-weekly intervals up to a cumulative activity of ~ 74 MBq. The primary endpoint included evaluating therapy response and disease control rate (DCR) using the RECIST 1.1 criteria. Additional secondary endpoints comprised clinical response assessment using EORTC QLQ-H&N35 questionnaire, Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group performance status (ECOG), analgesic score (AS), dose alterations of anti-hypertensive drugs (anti-HTN), and the safety and side-effect profile evaluation as per CTCAE criteria version 5.0. Results Following 225 Ac-DOTATATE treatment, morphological response revealed partial response in 50%, stable disease in 37.5%, and disease progression in 12.5%, with a DCR of 87.5%. Similarly, the symptomatic response was remarkable, and anti-HTN drugs were stopped in 25% and reduced in 37.5%. Another significant finding in our study revealed a morphologic DCR of 66.6% (2/3) in patients who failed previous lutetium-177 peptide receptor radionuclide therapy ( 177 Lu-PRRT). Regarding the KPS, ECOG, and AS performance scores, a notable improvement was observed post- 225 Ac-DOTATATE treatment. The QLQ-H&N35 symptom scores evaluated in seven H&N PGL patients showed significant improvement in all aspects. No improvement in sexual function was noted ( P  = 0.3559). Despite the significant reduction in the analgesic score post-treatment ( P  = 0.0031), the QLQ-H&N35 revealed only marginal significance concerning the intake of pain killers ( P  = 0.1723). No grade III/IV hematological, renal, and hepatological toxicities were noted. Conclusion The evidence from this study suggests 225 Ac-DOTATATE therapy is effective and safe in the treatment of advanced-stage PGLs and also reports a clear benefit even in patient’s refractory to the previous 177 Lu-PRRT.