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Prolonged life-threatening hypoglycaemia following dose escalation of octreotide LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour.

ABSTRACT: This paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This rendered our patient hospital dependent for glycaemic support including continuous dextrose infusion. Although this is a reported adverse effect with initiation of therapy, we describe successful initiation of short-acting octreotide as an inpatient followed by commencement of long-acting octreotide. Hypoglycaemic collapse occurred only after dose titration of long-acting octreotide. We outline the pitfalls of somatostatin analogue therapy and the mechanisms that may contribute to worsening hypoglycaemia. This rare side effect cannot be reliably predicted, necessitating close supervision and glucose monitoring during therapy. Our patient achieved disease stabilisation and gradual resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an emerging therapeutic option for metastatic neuroendocrine tumours with high efficacy and low toxicity. We present a brief but comprehensive discussion of currently available and novel therapies for insulin secreting pNETs.Hypoglycaemia due to malignant insulin secreting pNET is frequently severe and may be life-threatening despite supportive therapies.Octreotide can ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising effects in malignant pNETs that are surgically unresectable.Paradoxical worsening of hypoglycaemia may occur with octreotide initiation and dose titration, necessitating close supervision and glucose monitoring.PRRT is emerging as a therapeutic option with high efficacy and low toxicity.

SUBMITTER: Abell SK

PROVIDER: S-EPMC4313612 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Prolonged life-threatening hypoglycaemia following dose escalation of octreotide LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour.

Abell Sally K SK Teng Jessie J Dowling Anthony A Hofman Michael S MS MacIsaac Richard J RJ Sachithanandan Nirupa N

Endocrinology, diabetes & metabolism case reports 20150101

<h4>Unlabelled</h4>This paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This re ...[more]

PMID: 25755880

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Project description:BACKGROUND:Antitumor activity of the combination of somatostatin analogues (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in patients with neuroendocrine tumors (NETs) has been reported but not confirmed in prospective trials. MATERIALS AND METHODS:This prospective, multicenter, single-arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA octreotide 30 mg every 28 days in patients with advanced nonfunctioning well-differentiated gastrointestinal NETs (GI-NETs) that progressed in the last 12 months (ClinicalTrials.gov NCT01567488). Prior treatment with SSAs and any systemic or locoregional therapy was allowed except for mTOR inhibitors. Patients continued treatment until disease progression or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) at 12 months; secondary endpoints included early biochemical response, objective response rate (ORR) by RECIST v1.0, overall survival (OS), AEs, activation of mTOR pathway (insulin-like growth factor 1 receptor [IGF1R] and phosphoS6 [pS6] expression). RESULTS:Forty-three patients were included in the intent-to-treat analyses. After 12 months of treatment, 62.3% (95% confidence interval [CI] 48%-77%) of patients had not progressed or died. The 24-month PFS rate was 43.6% (95% CI 29%-58%). The confirmed ORR was 2.3%, and stable disease was 58.1%. Median OS was not reached after 24 months of median follow-up. Dose reductions and temporary interruptions due to AEs were required in 14 (33%) and 33 (77%) patients, respectively. The most frequent AEs were diarrhea, asthenia, mucositis, rash, and hyperglycemia. No correlation was observed between IGFR1 and pS6 expression and PFS/OS. CONCLUSION:The everolimus-octreotide combination provided clinically relevant efficacy in nonfunctioning GI-NETs, similar to the results of RADIANT-2 in functioning setting. IMPLICATIONS FOR PRACTICE:The EVERLAR study reports prospective data of somatostatin analogue in combination with everolimus in nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful activity and favorable toxicity profile that supports drug combination in this setting.

Dataset Information

Prolonged life-threatening hypoglycaemia following dose escalation of octreotide LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour.

Publications

Prolonged life-threatening hypoglycaemia following dose escalation of octreotide LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour.

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