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Pilot study: rapamycin in advanced hepatocellular carcinoma
Author(s) -
SchönigerHekele M.,
Müller C.
Publication year - 2010
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2010.04404.x
Subject(s) - medicine , hepatocellular carcinoma , tolerability , sirolimus , liver cancer , cirrhosis , gastroenterology , pi3k/akt/mtor pathway , cancer , oncology , stage (stratigraphy) , adverse effect , signal transduction , paleontology , biochemistry , chemistry , biology
Summary Background The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Aim To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC). Methods Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study. Results Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver‐Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months. Conclusion Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective.