Thymidylate synthase quantitation and in vitro chemosensitivity testing predicts responses and survival of patients with isolated nonresectable livertumors receiving hepatic arterial infusion chemotherapy

BACKGROUND. Patients with isolated. nonresectable liver tumors may receive regional hepatic arterial infusion (HAI) chemotherapy with response rates o f about 50%. The objective of this study was to investigate the value of th ymidylate synthase (TS) determination in combination with in vitro chemosen sitivity testing to predict the responses and survival of patients receivin g HAI. METHODS. TS mRNA expression was quantitated using a reverse transcriptionpo lymerase chain reaction technique with beta-actin as the internal standard. In vitro chemosensitivity testing was performed with tumor cell suspension s using the human tumor colony-forming assay (HTCA). RESULTS. An analysis of the test combination in 24 consecutive patients rev ealed that 77% (10 of 13) of the sensitive and 9% (1 of 11) of the resistan t patients had complete or partial clinical responses. Sensitive patients w ere 8.5-fold more likely to respond (P = 0.0036) and displayed with 32 mont hs (range, 5-75 months) a longer median survival than resistant patients wi th 17 months (range, 3-28 months, P = 0.003). Analysis of the Kaplan-Meier curves revealed that sensitive patients had a higher overall survival proba bility, as determined by the log rank test (P = 0.044). CONCLUSIONS. These results suggest that the clinical outcomes of patients r eceiving HAI therapy may be predictable with TS quantitation and HTCA. It i s possible, therefore, that this combination may be used in the future to s elect patients with liver tumors who will benefit from HAI before the start of regional chemotherapy. (C) 2000 American Cancer Society.