Pilot study: rapamycin in advanced hepatocellular carcinoma.
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.


OBJECTIVE
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.


CONCLUSIONS
Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective.
Schöniger-Hekele
M
M
Klinik Innere Medizin III, Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Vienna, Austria. maximilian.schoeniger-hekele@meduniwien.ac.at
Müller
C
C
D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D020123:Sirolimus