Biologic study of the effects of octreotide-LAR on growth hormone in unresectable and metastatic hepatocellular carcinoma

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 (ICF-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 clays (range, 27-444 clays). 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 (27.9ng/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 over-all survival (P=.0005 and P=.0173, respectively; 2-sided log-rank test). Conclusions: Octreotide-LAR lowered serum IGF-I and -II levels; however, this loweringdid 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.