Background: There are limited effective treatment options for metastatic insulinoma with intractable hypoglycaemia in which the cause of death is often hypoglycaemia rather than oncologic disease burden.
Methods: A retrospective audit identified six patients (3 men, age 55–77 years) with a diagnosis of metastatic insulinoma treated with peptide receptor chemo-radionuclide therapy (PRCRT) according to defined eligibility criteria for control of hypoglycaemia between July 2004 - June 2014 at the Peter MacCallum Cancer Centre. Five patients had prior inadequate response and/or intolerability of therapies including surgical-debulking, somatostatin-analogue therapy, diazoxide, glucocorticoids, glucagon, enteral feeding and cytotoxic chemotherapy; one patient was treated at diagnosis. Of patients with available tumour histology, three were ENETs Grade 1 (Ki,67 ≤2%) and one was Grade 2 (Ki,67 20%). All patients received 177Lu DOTA-octreotate (median cumulative dose 44.1 GBq) and radiosensitising 5FU chemotherapy; two patients also received either 111In DOTA-octreotide or 90Y DOTA-octreotate.
Results: All patients had complete resolution of hypoglycaemia after a median of 12 weeks (range 1–102 weeks) following treatment with PRCRT. Hyperglycaemic therapies were weaned and then ceased in all patients after a median of 4.5 weeks (range 1–14) and 32 weeks (range 1–128) respectively. Three patients were admitted for post-treatment flare of hypoglycaemia. Three patients had ongoing resolution of hypoglycaemia out to 35, 92 and 187 weeks follow-up. Recurrent hypoglycaemia occurred in three patients after 32, 77 and 222 weeks, and all were successfully re-treated with PRCRT. Median survival was not reached at median follow-up of 163 weeks. All patients demonstrated partial scintigraphic response to therapy and three of four patients with assessable lesions demonstrated partial response by RECIST criteria. Five patients with baseline elevated chromogranin A demonstrated a median reduction of 82% (range 51–94%) after PRCRT.
Conclusion: PRCRT is a highly effective therapy for relief of intractable hypoglycaemia in patients with metastatic insulinoma.