Bioembolisation for unresectable hepatocellular carcinoma: preliminary results of a translational research study.
Lack of effective treatment for surgically unresectable hepatocellular carcinoma has made this disease dismal. Although, systemic and/or locoregional chemotherapy and chemo-embolization are among the established treatment options, the results of these modalities are still far from being satisfactory. Systemic interferon administration is also used for the treatment of this disease however it has high toxicity rates. We conducted a pharmacology guided phase I/II study with the aim to explore the effect of hypoxy and interferon alpha-2a in vitro using the HepG2 Hepatoma cell line. We then translated the in-vitro results to the clinical setting and designed a treatment protocol. This schema consisted of lipiodol embolisation via a hepatic artery port in between two sets of seven loco-regional injections of IFNalpha-2a, 3 MU every other day. The in-vitro study revealed the best sequence of hypoxy and IFN as IFN-Hypoxy-IFN. Based on this finding, ten patients with HCC were treated with loco-regional IFN and lipiodolisation. Seven of them achieved partial response and the mean duration of response was 10 months. There was no Grade 4 toxicity. In conclusion, our preliminary clinical results suggest that the combined use of IFN and lipiodolisation in the optimal sequence may provide a new therapeutic option for patients with HCC.
Goker
E
E
Dept of Medicine, Ege University Hospital, Bornova, Izmir, Turkey. goker@med.ege.edu.tr
Sanli
U A
UA
Yuzer
Y
Y
Uslu
R
R
Karabulut
B
B
Memis
A
A
Coker
A
A
Mentes
A
A
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004396:Coloring Agents / Q000494:pharmacology; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D006499:Hepatic Artery / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D020128:Inhibitory Concentration 50; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007459:Iodized Oil / Q000737:chemistry; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome
D004396:Coloring Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D007459:Iodized Oil; D007372:Interferons; C022616:thiazolyl blue