TY - JOUR
TI - Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: Randomized placebo-controlled trial
AU - Dimitroulopoulos, D.
AU - Xinopoulos, D.
AU - Tsamakidis, K.
AU - Zisimopoulos, A.
AU - Andriotis, E.
AU - Panagiotakos, D.
AU - Fotopoulou, A.
AU - Chrysohoou, C.
AU - Bazinis, A.
AU - Daskalopoulou, D.
AU - Paraskevas, E.
JO - World Journal of Gastroenterology
PY - 2007
VL - 13
TODO - 23
SP - 3164-3170
PB - Baishideng Publishing Group Co
SN - 1007-9327
TODO - 10.3748/wjg.v13.i23.3164
TODO - alpha fetoprotein;  long acting drug;  octreotide;  pentetreotide in 111;  placebo;  somatostatin receptor, adult;  advanced cancer;  aged;  article;  cancer size;  cancer staging;  cancer survival;  clinical trial;  controlled clinical trial;  controlled drug release;  controlled study;  diarrhea;  drug dosage form comparison;  drug dose reduction;  drug formulation;  drug withdrawal;  female;  follow up;  human;  liver cell carcinoma;  liver cirrhosis;  liver scintiscanning;  major clinical study;  male;  outcome assessment;  protein expression;  quality of life;  randomized controlled trial;  survival time;  treatment duration;  virus infection
TODO - Aim: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). Methods: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. Results: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively. Conclusion: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC. © 2007 The WJG Press. All rights reserved.
Indications:30 patients with advanced hepatocellular carcinoma (multinodular 6, massive 20, and diffuse 4) somatostatin receptor-positive and cirrhosis (stage A 11 and stage B 19).
Patients:126 patients. Sandostatin group: 30 patients, 20 male and 10 female, mean age 69.4 years. 3 dropouts due to side effects. Placebo (control) group: 30 patients, 22 male and 8 female, mean age 69.5 years. SSTR-negative (SSTR-) group: 66 patients, 36 male and30 female, mean age 69.4 years. Patients were followed up for a period of 4 and 160 weeks.
TypeofStudy:This study estimated the extent of improvement of survival rate, with respect to tumor size and alpha-fetoprotein (AFP) levels, and quality of life of patients with advanced hepatocellular carcinoma-somatostatin receptor-positive (HCC-SSTR+) and A-B stage cirrhosis following Sandostatin treatment. Randomized, placebo-controlled clinical trial.
DosageDuration:0.5 mg sc tid (=1.5 mg daily) for 6 weeks; at the end of weeks 4 and 8, 20 mg im (as long acting repeatable); and at the end of week 12 and every 4 weeks, 30 mg im (as long acting repeatable). Duration: 12 weeks.
Results:At the end of the follow-up period, 1 patient death was recorded. A significantly higher mean survival time was noted for the Sandostatin compared with placebo and SSTR- groups (49 vs. 28 and 28 weeks, respectively; P<0.01). This trend was observed at 6 months, but without reaching statistical significance. After controlling for age, sex, HCC morphological characteristics, etiology, metastases, cirrhosis stage, BCLC stage and AFP levels, the Cox proportional hazard model revealed that patients in the Sandostatin (P<0.01) and placebo (P>0.05) groups had a 68.5% and 7% lower hazard of death, respectively as compared with the SSTR- group. In all 3 groups, a decreasing QLQ-C30 score was observed during the follow-up. During the first 12 months, a 22%, 39%, and 43% decrease was observed in the Sandostatin, placebo, and SSTR- groups, respectively. Sandostatin-treated patients presented a significantly higher QLQ-C30 score as compared with placebo and SSTR- patients (P>0.05).
AdverseEffects:A total of 30 adverse events were recorded at the end of follow up. 6 patients developed severe diarrhea leading to Sandostatin withdrawal.
FreeText:SSTR determination was conducted in all patients using scintigraphy with 111Indium-labeled octreotide. Patients with increased uptake (Krenning's score 3 and 4) were randomized to receive placebo or Sandostatin. Other tests: AFP levels, liver and renal function, tumor size (dual phase helical computer tomography scan), and QLQ-C30 (quality of life assessment).
AuthorsConclusions:The proposed therapeutic approach has shown to improve survival and quality of life in SSTR positive patients with advanced HCC and, despite the high cost, it seems to be an attractive therapeutic option for those who have no possibility for other therapeutic modalities such as liver transplantation, surgical resection, PEI [percutaneous ethanol injection] or TACE [transcatheter arterial chemoembolization].
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