Biologic study of the effects of octreotide-LAR on growth hormone in unresectable hepatoma Free

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PURPOSE: Animal models suggest that growth hormone (GH) participates in the carcinogenesis of hepatocellular carcinoma (HCC), however no human clinical studies have explored this hypothesis. We conducted this study to correlate the effect of octreotide-LAR, a suppressor of GH, on insulin-like growth factors -I (IGF-I) and -II (IGF-II), surrogates of GH, with response and survival in patients with unresectable HCC.

METHODS: We conducted a phase II, single-institution trial of octreotide-LAR (30 mg intramuscularly every four weeks) in 15 patients with advanced HCC; in addition, serum IGF-I and IGF-II levels were monitored with treatment.

RESULTS: Patients (median CLIP score 2; median Okuda stage II; median ECOG performance status 1) were treated a median 2.0 cycles. No responses occurred. Median overall survival (OS) was 116 days (range, 27 to 937 days) and median progression-free survival (PFS) was 60 days (range, 27 to 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 IGF-I decreased from baseline (42.2 ng/ml; range, 14.2 to 109 ng/ml) to day 29 (27.9 ng/ml; range, 5.7 to 71.1 ng/ml) and median IGF-II decreased from baseline (25,000 ng/ml; range, 12,400 to 93,600 ng/ml) to day 29 (18,400 ng/ml range, 4,061 to 79,400 ng/ml) (two-sided P-value<0.006 and <0.04, respectively; Wilcoxon signed-rank test on log transformed data). This suppression did not correlate inversely with clinical activity.

CONCLUSIONS: There were no responses and median PFS and OS were similar to historical patients not on treatment. Octreotide-LAR consistently lowered IGF-I and IGF-II serum levels; however, this suppression did not correlate inversely with clinical activity.