Background: Pancreatic cancer (PC) is an aggressive tumor that accounts for 3-4% of all cancers. Unfortunately, 80% of PCs are diagnosed when the disease has already given regional or distant metastases, and the 5-year overall survival rate is approximately 5%. Neuroendocrine pancreatic tumors (pNETs) are much less common (<5%) than exocrine tumors and are usually nonfunctional. The rare functional pNETs overproduce hormones, consequently exhibiting different hormone-related symptoms. In all patients with PC unsuitable for surgery or who refuse surgery, two 4-drug regimens, named PEFG (cisplatin, epirubicin, 5FU, gemcitabine) and FOLFIRINOX (folinic acid, 5FU, irinotecan, oxaliplatin), have been shown to give better results towards gemcitabine alone. Recently, nab-paclitaxel (nanoparticle albumin-bound paclitaxel) plus gemcitabine (NAB-P/GEM) use has been suggested. Clinical case: A 57-year-old man, with a history of hyperthyroidism and type II diabetes mellitus, underwent hematological screening complaining indolent abdominal and lumbar pain, progressive weight loss, and mild jaundice. The main biochemical data were hyperbilirubinemia, hypercalcemia (3.8 mmol/L), elevated chromogranin A (1,237 ng/mL), low TSH, low PTH (0.9 ng/L), and high levels of parathyroid hormone-related protein (PTHrP=72 pmol/L). The CT-scan depicted a 4-cm mass at the head of pancreas involving the surrounding structures, multiple focal liver lesions, and several vertebral and rib metastases. MRI confirmed the presence of liver metastases, and a CT-guided cutting needle biopsy revealed liver metastasis from a moderately differentiated (G2) NET (Ki-67 index=15%). The ECOG performance status of the patient was 4. However, he refused surgery, and thus a NAB-P/GEM was proposed and accepted. NAB-P (125 mg/m2) and GEM (1000 mg/m2) on day 1, 8, 15 every 28 days for 4 cycles plus octreotide long-acting release (LAR), 30 mg every 4 weeks, were administered. With the aim of reducing hypercalcemia, zoledronic acid (ZA), 4 mg every 4 weeks was used. No grade 3-4 adverse events occurred, and the treatment continued until 6 cycles. A significant objective response detected on CT was obtained at 4-month follow-up. Unfortunately, serum calcium levels did not change significantly, and thus the patient received denosumab (120 mg on days 1, 2, 4, 8, 12, 16, 20 and then 120 mg every 2 weeks). A normalization of serum calcium levels was obtained after 2 weeks. Conclusions: Cancer-related hypercalcemia (CRH) is the second cause of hypercalcemia, and is observed in up to 20% of patients with advanced malignancy. In patients with pNETs, CRH is very uncommon, and is usually related to PTHrP production by the cancer cells (humoral hypercalcemia). Patients with CRH due to pNETs can be treated with a combination of chemotherapy, and ZA or denosumab. Peptide receptor radionuclide therapy with 177Lutetium DOTA-octreotate administration should be reserved for unresponsive patients.

Severe cancer-related hypercalcemia in a patient with unresectable neuroendocrine pancreatic malignant tumor treated with NAB-P/GEM chemotherapy and denosumab

LUMACHI, FRANCO;
2015

Abstract

Background: Pancreatic cancer (PC) is an aggressive tumor that accounts for 3-4% of all cancers. Unfortunately, 80% of PCs are diagnosed when the disease has already given regional or distant metastases, and the 5-year overall survival rate is approximately 5%. Neuroendocrine pancreatic tumors (pNETs) are much less common (<5%) than exocrine tumors and are usually nonfunctional. The rare functional pNETs overproduce hormones, consequently exhibiting different hormone-related symptoms. In all patients with PC unsuitable for surgery or who refuse surgery, two 4-drug regimens, named PEFG (cisplatin, epirubicin, 5FU, gemcitabine) and FOLFIRINOX (folinic acid, 5FU, irinotecan, oxaliplatin), have been shown to give better results towards gemcitabine alone. Recently, nab-paclitaxel (nanoparticle albumin-bound paclitaxel) plus gemcitabine (NAB-P/GEM) use has been suggested. Clinical case: A 57-year-old man, with a history of hyperthyroidism and type II diabetes mellitus, underwent hematological screening complaining indolent abdominal and lumbar pain, progressive weight loss, and mild jaundice. The main biochemical data were hyperbilirubinemia, hypercalcemia (3.8 mmol/L), elevated chromogranin A (1,237 ng/mL), low TSH, low PTH (0.9 ng/L), and high levels of parathyroid hormone-related protein (PTHrP=72 pmol/L). The CT-scan depicted a 4-cm mass at the head of pancreas involving the surrounding structures, multiple focal liver lesions, and several vertebral and rib metastases. MRI confirmed the presence of liver metastases, and a CT-guided cutting needle biopsy revealed liver metastasis from a moderately differentiated (G2) NET (Ki-67 index=15%). The ECOG performance status of the patient was 4. However, he refused surgery, and thus a NAB-P/GEM was proposed and accepted. NAB-P (125 mg/m2) and GEM (1000 mg/m2) on day 1, 8, 15 every 28 days for 4 cycles plus octreotide long-acting release (LAR), 30 mg every 4 weeks, were administered. With the aim of reducing hypercalcemia, zoledronic acid (ZA), 4 mg every 4 weeks was used. No grade 3-4 adverse events occurred, and the treatment continued until 6 cycles. A significant objective response detected on CT was obtained at 4-month follow-up. Unfortunately, serum calcium levels did not change significantly, and thus the patient received denosumab (120 mg on days 1, 2, 4, 8, 12, 16, 20 and then 120 mg every 2 weeks). A normalization of serum calcium levels was obtained after 2 weeks. Conclusions: Cancer-related hypercalcemia (CRH) is the second cause of hypercalcemia, and is observed in up to 20% of patients with advanced malignancy. In patients with pNETs, CRH is very uncommon, and is usually related to PTHrP production by the cancer cells (humoral hypercalcemia). Patients with CRH due to pNETs can be treated with a combination of chemotherapy, and ZA or denosumab. Peptide receptor radionuclide therapy with 177Lutetium DOTA-octreotate administration should be reserved for unresponsive patients.
2015
Proceedings of the Endo-Bridge 2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3167782
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