Absence of therapeutic efficacy of the somatostatin analogue lanreotide in advanced primary hepatic cholangiocellular cancer and adenocarcinoma of the gallbladder despite in vivo somatostatin-receptor expression.

BACKGROUND: Carcinoma of the biliary system is a rare tumour entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma and reports of expression of receptors for somatostatin (SST), we performed a phase II study to evaluate the clinical potential of the long-acting SST analogue lanreotide (LAN) for treatment of this disease.
METHODS: Twenty consecutive patients with histologically verified primary hepatic cholangiocellular cancer or primary adenocarcinoma of the gallbladder were enrolled in the study. Before initiation of therapy, SST-receptor scintigraphy using 111In-DOTA-LAN was carried out in eight patients to check for in vivo expression of SST receptors. Thirty milligrams of a slow-release formulation of LAN was administered by deep intramuscular injection every 2 weeks until progression or patients wished to withdraw. Restaging by means of computed tomography was performed every 8 weeks, and response was assessed according to World Health Organisation standard criteria. In addition, weight, performance status, analgesic intake and subjective pain perception were recorded every 4 weeks, along with evaluation of tumour markers CEA and Ca 19-9.
RESULTS: Tumour sites were visualized by means of 111In-DOTA-LAN in all 8 patients. A total of 161 injections were administered, the median number per patient being 5 (range 2-36). Side effects were generally mild, only two patients complained of mild nausea and one patient had meteorism attributed to therapy. Therapeutic results, however, were disappointing, with only one patient demonstrating complete remission (CR), which lasted for 18 months before diagnosis of recurrence. Four patients had stable disease (SD) lasting between 3.5 and 9+ months accompanied by weight gain and improvement in performance status in 2 cases, while the remaining 15 patients progressed during therapy. The median time to progression was 2.5 months (range 1-18), and the median survival was 4.5 months (range 1.5-18+ months). No clear-cut correlation between scan result and therapeutic outcome could be demonstrated, as not only the patient with CR and two with SD, but also five patients with progressive disease had a positive scan result.
CONCLUSION: Our data show that adenocarcinomas of the gallbladder and hepatic cholangiocellular carcinomas express SST receptors in vivo as judged by 111In-DOTA-LAN scintigraphy. Despite this fact, LAN did not display therapeutic activity in this study.