title: Phase I study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer.
abstract: OBJECTIVE
  Pasireotide LAR (SOM230 LAR) is a cyclohexapeptide engineered to bind to multiple somatostatin receptor subtypes to mimic the action of naturally occurring somatostatin with higher affinity to these receptors than octreotide and is a potent inhibitor of insulin-like growth factor-1 (IGF-1). Somatostatin receptors and IGF receptors are highly expressed in pancreatic cancer, thereby potentially making it a valuable target. This phase I study evaluated safety, tolerability and preliminary tumor response of pasireotide LAR in combination with gemcitabine in locally advanced or metastatic pancreatic cancer.
  
  
  METHODS
  Patients with previously untreated metastatic pancreatic cancer were included. A 3 + 3 dose-escalation design was used. Patients received gemcitabine on days 1, 8 and 15 and pasireotide LAR IM monthly in a 28-day cycle. Two dose levels of pasireotide LAR were planned: 40 mg IM and 60 mg. Cohort was expanded by ten more patients at the highest tested dose to further assess the safety and efficacy.
  
  
  RESULTS
  Twenty patients were consented on this trial, and 16 patients were evaluable for safety and efficacy. No dose-limiting toxicities were observed. Two out sixteen patients (12%) had partial response, and nine of sixteen (56%) had stable disease as best response. Median progression-free survival was 4.1 months (range 1-16 months), and median overall survival was 6.9 months (range 1-25 months). Most common grade 3 or 4 toxicities were hyperglycemia (n = 5), hyperbilirubinemia (n = 1) and thrombocytopenia (n = 2). Median baseline IGF-1 level was lower in patients with stable disease than in those with progressive disease (63 vs 71 ng/ml).
  
  
  CONCLUSIONS
  Pasireotide in combination with gemcitabine was well tolerated with disease control rate of 68%. Larger trials are needed in the future to establish its efficacy in the treatment of pancreatic cancer.
  
  
  BACKGROUND
  NCT01385956.
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA.
authors.forename: Yaman
authors.initials: Y
authors.lastname: Suleiman
authors.forename: Amit
authors.initials: A
authors.lastname: Mahipal
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.forename: Erin M
authors.initials: EM
authors.lastname: Siegel
authors.forename: Helen
authors.initials: H
authors.lastname: Jump
authors.forename: William J
authors.initials: WJ
authors.lastname: Fulp
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Springett
authors.forename: Richard
authors.initials: R
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D013004:Somatostatin; C517782:pasireotide; D000093542:Gemcitabine