Can peptide receptor radionuclide therapy be safely applied in florid bone metastases? A pilot analysis of late stage osseous involvement.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
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A
Sabet
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Khalaf
C J
CJ
Yong-Hing
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Sabet
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Haslerud
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H
Ahmadzadehfar
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S
Guhlke
F
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Grünwald
H-J
HJ
Biersack
Samer Ezziddin, MD, Department of Nuclear Medicine, University Hospital, Sigmund-Freud-Str. 25, 53105 Bonn, Germany, Tel. +49/228/28 71 91 74,, Fax +49/(0)228/28 79 01 91 74, e-mail: samer.ezziddin@ukb.uni-bonn.de.
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Ezziddin
D000328:Adult; D000368:Aged; D001855:Bone Marrow Diseases / Q000000981:diagnostic imaging / Q000209:etiology*; D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010865:Pilot Projects; D011832:Radiation Injuries / Q000000981:diagnostic imaging / Q000209:etiology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome
C554548:177Lu-octreotate; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; D015282:Octreotide
177Lu-octreotate; Bone metastases; NET; PRRT