Can peptide receptor radionuclide therapy be safely applied in florid bone metastases?

Summary

Aim: Highly advanced metastatic bone disease with extensive osseous infiltration of neuroendocrine tumours (NET) may preclude patients from treatment with peptide receptor radionuclide therapy (PRRT) in concern about haematotoxicity. This study aims to assess the safety and efficacy of PRRT with ¹⁷⁷Lu-octreotate in a patient cohort with this condition. Patients, methods: 41 PRRT courses were performed in 11 patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET) and florid bone metastases (severely advanced widespread metastatic bone disease). A mean activity of 6.95 GBq ¹⁷⁷Lu-octreotate was administered per treatment cycle, aimed at four courses with standard intervals of 3 months. Haematological parameters were determined prior to each treatment course, in 2-4 weeks intervals between the courses, 8-12 weeks after the last course of PRRT and in 3 monthly intervals thereafter. Toxicity was recorded using Common Terminology Criteria for Adverse Events v3.0. Restaging was performed 3 months after termination of PRRT with CT/MRI and functional imaging (modified MDA criteria). Results: Significant (grade III-IV), reversible haematotoxicity occurred in 4 (35%) patients and after 10 (24%) administrations. It either resolved spontaneously (1 patient) or was controlled by supportive measures (3 patients), such as blood transfusions (3 patients) or deferral of the subsequent therapy cycle (1 patient). Patients returned to baseline blood values within up to 23 months after termination of PRRT. The observed treatment response of bone metastases consisted of a partial response in 2, a minor response in 1, stable disease in 7, and progressive disease in 1 patient. Of the 4 patients with metastatic bone pain, 1 experienced complete and 3 partial resolution of symptoms within 3-10 weeks after commencement of PRRT. Conclusion: These preliminary data indicate that PRRT with ¹⁷⁷Lu-octreotate can be safely applied even in florid bone metastases with extensive, severely advanced osseous replacement. The higher myelosuppression rate was not associated with serious complications and should not preclude patients from being treated and potentially experiencing remarkable treatment efficacy despite the very advanced stage.

Zusammenfassung

Hintergrund: Eine massiv fortgeschrittene Knochenmetastasierung mit extensiver Knochenmarkinfiltration durch neuroendokrine Tumore (NET) kann wegen der befürchteten Hämatotoxizität zum Ausschluss von der Peptid-Radiorezeptortherapie (PRRT) führen. Sicherheit und Wirksamkeit von ¹⁷⁷Lu-DOTA- Octreotat (¹⁷⁷Lu-Octreotat) in einer solchen Situation sollen anhand eines entsprechenden Patientenkollektives retrospektiv untersucht werden. Patienten, Methodik: 41 PRRT Zyklen (mittlere Aktivität: 6,95 GBq ¹⁷⁷Lu- Octreotat, 4 intendierte Zyklen, Standardintervall: 3 Monate) wurden in 11 Patienten mit gastroenteropankreatischen NET (GEP- NET) und weit fortgeschrittener Knochenme- tastasierung mit ausgedehnter Knochenmarksinfiltration verabreicht. Blutbildparameter wurden vor jedem Behandlungszyklus, in 2- bis 4-wöchigen bzw. nach Abschluss der PRRT in 8- bis 12-wöchigen Intervallen bestimmt; Wertung der Toxizität nach Common Terminology Criteria for Adverse Events v3.0; Restaging 3 Monate nach Abschluss der PRRT mittels CT/MRT und funktioneller Bildgebung, Ansprechen eingeteilt nach modif. MDA Kriterien. Ergebnisse: Eine signifikante (°III-IV) Hämatotoxizität trat bei 4 (35%) Patienten bzw. nach 10 (24%) Zyklen auf, jeweils mit Spontanerholung oder Korrektur durch supportive Maßnahmen. Die Rückkehr der Zellzahlen auf Ausgangsniveau erfolgte innerhalb von bis zu 23 Monaten nach Ab- schluss der PRRT. Das Ansprechen der Knochenmetastasen bestand in einer “partial response” bei 2, einer “minor response” bei 1, “stable disease” bei 7, und “progressive disease” bei 1 Patienten. Von den 4 Patienten mit tumorbedingten Knochenschmerzen erfuhr ein Patient eine komplette und 3 Patienten eine partielle Rückbildung (innerhalb 3-10 Wochen nach Beginn der PRRT). Schlussfolgerung: Die vorläufigen Daten deuten auf eine sichere Anwendbarkeit der PRRT mittels ¹⁷⁷Lu-Octreotat selbst bei maximaler Knochenmetastasierung mit extensiver Knochenmarksverdrängung. Die beobachtete höhere Rate an Myelosuppressio- nen war klinisch unproblematisch und sollte nicht zu einem Vorenthalten des potenziell sehr wirksamen Verfahrens führen, welches selbst in stark fortgeschrittenem Stadium noch zu beachtlicher Stabilisierung oder Teilremission führen kann.

Keywords

Bone metastases - PRRT - ¹⁷⁷Lu-octreotate - NET

Schlüsselwörter

PRRT - Peptid-Radiorezeptortherapie - neuroendokrine Tumore - Knochenmetastasierung - Hämatotoxizität - 177Lu-DOTA.Octreotat

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