Chemosensitivity of primary hepatic neoplasms: a potential new approach to the treatment of hepatoma.

Background/aims: Standard chemotherapy approaches for hepatic neoplasms are effective in only 20-30% of cases. The vast majority of patients treated with chemotherapy experience little or no benefit with considerable toxicity. In an effort to identify specific agents potentially effective in individual cases, 22 individuals with a hepatoma were biopsied and their tumor cells were grown in culture such that the expanded tumor cell population could be assessed for chemosensitivity to 14 different commonly used chemotherapeutic agents.

Methodology: Each agent was tested in 6 wells at 6 different doses scanning a range of concentrations known to occur in vivo corresponding to subpharmacologic levels to suprapharmacologic levels. The in vitro response of each tumor for each agent was determined on a 0- to 5-point scale where 0 equals not sensitive and 5 equals extremely sensitive. Each of the tumors was successfully grown and expanded in culture over a 30- to 40-day period. Three individuals had their tumors biopsied and tested twice at 2 different time points. In addition, 2 liver specimens determined to be non-neoplastic liver specimens after removal were expanded in culture as controls to determine the sensitivity of normal non-neoplastic cells to the same 14 chemotherapeutic agents.

Results: Assuming that tumors would be clinically sensitive to an agent if their in vitro sensitivity score is 3 or above, then only a minority of tumors could be identified as chemosensitive to the 14 agents tested. Moreover, of the 2 agents (doxorubicin and cisplatin) used most often clinically, only 14 of the 22 tumors were sensitive to either of these agents. Only 8 of the tumors demonstrated an in vitro sensitivity score of 5 for either of these 2 agents. Specifically, only 11 of the 22 tumors were sensitive to doxorubicin and only 9 were sensitive to cisplatin. In contrast, 14 of the tumors showed in vitro sensitivity to 1 or more of the other 12 agents utilized for chemosensitivity determinations.

Conclusions: These data demonstrate that hepatic tumors can be 1) grown in vitro and 2) tested for in vitro chemosensitivity. These data suggest that this methodology may identify tumors that are sensitive to specific chemotherapeutic agents and assist in the determination of which agents might be most useful in a given case. Selecting a chemotherapeutic agent for use using this methodology, should improve efficacy while toxicity would be minimized.