Endocrine Abstracts

Outpatient theranostics began 30 years ago in Western Australia with world-first phase 1/11 clinical trials of Samarium-153-EDTMP for pain palliation of skeletal metastases prospective individualised dosimetry in each patient, based upon a calculated maximum radiation absorbed dose of 2Gy to haemopoietic marrow was performed by quantitative whole-body gamma imaging, to prescribe the safe effective administered therapeutic activity, which was then given on the same day as an outpatient.

The same simple, practical outpatient theranostic methodology was subsequently applied to Rhenium-188-HEDP, prepared in-house using an on-site Tungsten-188/Rhenium-188 generator for inexpensive, sustainable, practical control of bone cancer pain.

In 1999, we introduced Iodine-131 rituximab radioimmunotherapy (RIT) of relapsed/refractory non-Hodgkin Lymphoma (NHL) using an outpatient theranostic approach with a prescribed individual administered activity (GBq) on the basis of a prospectively measured whole body radiation absorbed dose of 0.75Gy (predicated upon 2Gy to red marrow). The efficacy and lack of toxicity of this theranostic approach was subsequently demonstrated in first-line outpatient RIT of advanced follicular NHL. Our contemplated introduction of Lutetium-177-rituximab will obviate the requirement for such patient isolation within the community.

We have administered Lutetium-177-octreotate exclusively as an outpatient therapy of NETs for over a decade. The radiation safety of this simple, practical and relatively inexpensive outpatient approach has been documented in a formal study of radiation exposure to hospital personnel, patient’s family members and the public and measured rates are in conformity with international guidelines.

The enhanced efficacy of our outpatient theranostic Lutetium–177-Octreotate PRRT of GEP-NETs, when combined with radiosensitizing chemotherapy with capecitabine and temozolomide is currently under formal multicentre randomised controlled trial throughout Australia–CONTROL–NETs (ACTRN12615000909527).

We have recently reviewed the short-term and long-term myelotoxicity of our outpatient theranostic Lutetium-177-Octrotate capecitabine/temozolomide PRRT of GEP-NETs and shown it to be modest, provided that patients have not been heavily pre-treated with alkylating agents. We are now currently reviewing the myelotoxicity profile of our out-patient theranostics Lutetium-177-PSMA radiopeptide therapy of advanced prostate cancer.

References

1.Turner JH, Claringbold PC, Hetherington EL, et al. A Phase 1 study of Samarium-153 Ethylenediaminetetra methylene Phosphonate Therapy for Disseminated Skeletal Metastases J Clin Oncol 1989 17(12) 1926-31.

2. Leahy MF, Turner JH. Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131 I – rituximab in routine clinical practice: 10 year single institution experience of 142 consecutive patients. Blood 2011:117-45.

3. Mc Quillan AD. Macdonald WBG, Turner JH Phase II study first-line Iodine-131-rituximab radioimmunotherapy follicular non-Hodgkin lymphoma and prognostic Fluorine-18-FDG PET: Leukaemia and Lymphoma 2014:19:1-7.

4. Calais PJ Turner JH Outpatient Iodine-131-rituximab radioimmunotherapy of non-Hodgkin lymphoma: A study in safety: Clin Nucl Med 2012 37 732-737.

5. Calais PJ, Turner JH: Radiation Safety of outpatient Lutetium-177 octreotate radiopeptide therapy of neuroendocrine tumours: Ann Nucl Med 2014 28(6) 531-539.

6. Claringbold PG, Turner JH: Pancreatic Neuroendocrine Tumour Control: Durable Objective Response to combination 177 Lu-Octreotate – Capecitabine-Temozolomide Radiopeptide Chemotherapy: Neuroendocrinol 2016:103:432-439.

7. Kesavan M.Turner JH. Myelotoxicity of Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumours: A Decade of Experience. Cancer Biother Radiopharm 2016 31:6:189-198.