A Phase II Study of Long-Acting Octreotide in Patients With Advanced Hepatocellular Carcinoma and CLIP Score of 3 or Higher.
BACKGROUND
Studies of octreotide in hepatocellular carcinoma have yielded conflicting results. Since past studies have excluded patients with highly advanced disease and given the fact that octreotide offers several potential physiologic benefits in patients with advanced cirrhosis, such as improving renal physiology and decreasing portal venous pressure, we designed a trial to examine the survival of patients with both advanced HCC and advanced cirrhosis as defined by a CLIP score of 3 or higher.


METHODS
The study was designed as a phase-II, multicenter trial, enrolling patients with advanced HCC in three tertiary care academic centers in the United States. The primary objective was to verify whether long-acting octreotide will extend median survival from 5 months to 8.75 months for patients with CLIP scores of 3 or higher, representing a 75% increase in median survival time. Secondary objectives included assessing safety and tolerability in this patient population.


RESULTS
Twenty-two patients were enrolled from 2003 to 2005. The mean age was 66, with the majority of patients being men. The median CLIP score was 4 with a median KPS of 80%. Ten of 22 patients died without evidence of progression of HCC. The median TTP was 5.7 months (95% confidence interval [CI], 2.8-10.7). The median PFS time was approximately 3 months (95% CI, 1.7-5.7). The median OS time was 4.5 months (95% CI, 2.3-8) and therefore did not meet the established primary end point. Six of 22 patients achieved an OS of greater than 10 months. One patient experienced a radiographic partial response.


CONCLUSIONS
Long-acting octreotide was not associated with a survival benefit in patients with significant liver disease related to HCC. The identification of one patient with disease regression and a subgroup of patients with significantly greater survival underscores the need to gain a better understanding of the role of somatostatin receptors on HCC cells before further clinical testing of this drug in HCC patients.
Shah
Usman
U
Division of Medical Oncology, University of North Carolina, Chapel Hill, NC.
O'Neil
Bert
B
Allen
Jill
J
Goldberg
Richard M
RM
Bernard
Steven
S
Moore
Dominic
D
Venook
Alan P
AP
Morse
Michael M
MM