Biologic study of the effects of octreotide-LAR on growth hormone in unresectable and metastatic hepatocellular carcinoma
Attia, S.; Holen, K.D.; Thomas, J.P.; Richie, K.; Dzelak, T.; Teeter, K.; Warren, D.; Bilger, A.; Fine, J.; Eickhoff, J.; Drinkwater, N.; Mulkerin, D.; Morgan-Meadows, S.
Clinical Advances in Hematology and Oncology H&o 6(1): 44-54
2008
ISSN/ISBN: 1543-0790 PMID: 18322441 Document Number: 618002
Animal models suggest that growth hormone participates in hepatocarcinogenesis. 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. 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. 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). 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.