title: Biologic study of the effects of octreotide-LAR on growth hormone in unresectable and metastatic hepatocellular carcinoma.
abstract: BACKGROUND
  Animal models suggest that growth hormone participates in hepatocarcinogenesis.
  
  
  OBJECTIVE
  To correlate the effect of octreotide long-acting release (LAR) on insulin-like growth factor-I (IGF-I) and -II (IGF-II) with response and survival in patients with unresectable and metastatic hepatocellular carcinoma.
  
  
  METHODS
  We conducted a phase II, single-institution trial of octreotide-LAR (30 mg intramuscularly every 4 weeks) in 15 patients while monitoring serum IGF-I and -II levels.
  
  
  RESULTS
  Patients (median CLIP score 2, Okuda stage II, and ECOG performance status 1) were treated for a median of 2.0 cycles. No responses occurred. Median overall survival was 116 days (range, 27-937 days) and median progression-free survival was 60 days (range, 27-444 days). One patient had prolonged stable disease (16 months). There were no grade 4 and four grade 3 toxicities: abdominal cramping, elevated creatinine, diarrhea, and dyspnea. Median serum IGF-I decreased from baseline (42.2 ng/mL; range, 14.2-109 ng/mL) to day 29 (27.9 ng/mL; range, 5.7-71.1 ng/mL), and median serum IGF-II decreased from baseline (25,000 ng/mL; range, 12,400-93,600 ng/mL) to day 29 (18,400 ng/mL; range, 4,061-79,400 ng/mL; 2-sided P<.006 and P<.04, respectively; Wilcoxon signed rank test). This suppression did not correlate with clinical activity. Baseline serum IGF-I >30 ng/mL was associated with greater progression-free survival and overall survival (P=.0005 and P=.0173, respectively; 2-sided log-rank test).
  
  
  CONCLUSIONS
  Octreotide-LAR lowered serum IGF-I and -II levels; however, this lowering did not correlate with clinical activity. There were no responses, and progression-free survival and overall survival were similar to historical patients not on treatment. Baseline serum IGF-I predicted prognosis.
authors.affiliation: Department of Medicine, Section of Hematology and Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Attia
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Holen
authors.forename: James P
authors.initials: JP
authors.lastname: Thomas
authors.forename: Kelly
authors.initials: K
authors.lastname: Richie
authors.forename: Torie
authors.initials: T
authors.lastname: Dzelak
authors.forename: Kristine
authors.initials: K
authors.lastname: Teeter
authors.forename: Deb
authors.initials: D
authors.lastname: Warren
authors.forename: Andrea
authors.initials: A
authors.lastname: Bilger
authors.forename: Jason
authors.initials: J
authors.lastname: Fine
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.forename: Norman
authors.initials: N
authors.lastname: Drinkwater
authors.forename: Daniel
authors.initials: D
authors.lastname: Mulkerin
authors.forename: Sherry
authors.initials: S
authors.lastname: Morgan-Meadows
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects*; D007335:Insulin-Like Growth Factor II / Q000187:drug effects*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D015282:Octreotide / Q000494:pharmacology*; D011379:Prognosis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D015282:Octreotide