R018

Hypercalcaemia due to PTH-related peptide (PTHrP) secreting pancreatic neuroendocrine tumour, responsive to sunitinib treatment

Kalyan Gurazada, Christina Thirlwell, Martyn Caplin, Bernard Khoo, Tim Meyer

Royal Free Neuroendocrine Tumour Unit

A 33 year old lady presented in 2002 with a large unresectable pancreatic NET of approximately 14 cm in size.

She had FCiSt (5-FU, cisplatin, streptozocin) chemotherapy x6 cycles in 2003, and cycles 2006, leading to stable disease and a reduction in chromogranin A from 123 to <10 pmol/l.

She was also noted to have a slightly elevated calcium of 2.61mmol/l, PTH 1.1 pmol/l (low) and PTHrP 1.3 pmol/l (ref range 0.7 to 1.8). This was considered consistent with a mild PTHrP related hypercalcaemia.

She remained relatively stable until 2010 when the calcium started rising up to 2.9 mmol/l: she was symptomatic with polyuria and polydipsia.  PTHrP was 1.3 pmol/l. At the same time her chromogranin A rose to 181pmol/l, chromogranin B 213pmol/l, and somatostatin >1000pmol/l. The tumour size was stable at ~14cm.

She was treated with zolendronic acid 5mg and this led to a transient drop in calcium of 2.49mmol/l.

However within five months the calcium rose back to 2.93mmol/l. She was given further three doses of zolendronic acid at 3 weekly intervals with no sustained response, i.e. the PTHrP hypercalcaemia had become resistant to zoledronic acid. Octreotide LAR treatment was ineffective in controlling calcium levels.

She was therefore commenced on sunitinib 37.5mg od, and her calcium fell to 2.60mmol/l within a month of initiation. For the first time the PTHrP was undetectable at <0.7 pmol/l.

MRI scanning showed also a significant reduction in size of the PNET from 14.3cm to 13.5cm, plus a reduction in vascularity within six weeks of sunitinib treatment.

This case illustrates the relatively rare presentation of a PTHrP secreting pancreatic NET, how this condition can become resistant to potent bisphosphonate and somatostatin analogue treatment, and how sunitinib has been effective at inducing a partial response.