Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors

Patients with nonresectable metastatic neuroendocrine tumors (NETs) experience symptoms of hormone hypersecretion including diarrhea, flushing, and bronchoconstriction, which can interfere with quality of life [Anthony and Vinik (2011) Pancreas, 40:987]. Treatment with a long-acting release formulation of octreotide, a somatostatin analog, can help to alleviate these symptoms. Although high doses of octreotide are often required for adequate symptom control, the relationship between octreotide dose escalation and symptom control in the NET context is not well quantified in the literature. A retrospective chart review was conducted of nonresectable metastatic NET patients who received a dose greater than 30 mg intramuscular octreotide long-acting formulation (O-LAR) at any time between January 2005 and December 2011 at the British Columbia Cancer Agency (BCCA). The association between dose escalation of O-LAR, chromogranin A (CGA), 24-h urine 5-hydoxyindoacetate (5-HIAA), symptom control, and radiological progression was explored. Dose escalation of O-LAR was associated with improved symptom control in NET patients who were refractory to the standard dose levels. Reduction of serum CGA & 5-HIAA levels by at least 10% was observed in 31% and 23% respectively. Retrospective review of imaging did not document any reductions in tumor volume. Higher doses of O-LAR are associated with improved symptom control in NET patients. The variability in tumor marker levels in response to O-LAR dose escalation may indicate that tumor marker levels may not be an accurate assessment of therapeutic efficacy.