Thymidylate synthase quantitation and in vitro chemosensitivity testing predicts responses and survival of patients with isolated nonresectable liver tumors receiving hepatic arterial infusion chemotherapy.
BACKGROUND
Patients with isolated, nonresectable liver tumors may receive regional hepatic arterial infusion (HAI) chemotherapy with response rates of about 50%. The objective of this study was to investigate the value of thymidylate synthase (TS) determination in combination with in vitro chemosensitivity testing to predict the responses and survival of patients receiving HAI.


METHODS
TS mRNA expression was quantitated using a reverse transcription-polymerase chain reaction technique with beta-actin as the internal standard. In vitro chemosensitivity testing was performed with tumor cell suspensions using the human tumor colony-forming assay (HTCA).


RESULTS
An analysis of the test combination in 24 consecutive patients revealed that 77% (10 of 13) of the sensitive and 9% (1 of 11) of the resistant patients had complete or partial clinical responses. Sensitive patients were 8.5-fold more likely to respond (P = 0.0036) and displayed with 32 months (range, 5-75 months) a longer median survival than resistant patients with 17 months (range, 3-28 months, P = 0.003). Analysis of the Kaplan-Meier curves revealed that sensitive patients had a higher overall survival probability, as determined by the log rank test (P = 0.044).


CONCLUSIONS
These results suggest that the clinical outcomes of patients receiving HAI therapy may be predictable with TS quantitation and HTCA. It is possible, therefore, that this combination may be used in the future to select patients with liver tumors who will benefit from HAI before the start of regional chemotherapy.
Department of General Surgery, University of Ulm, Ulm, Germany.
K H
KH
Link
M
M
Kornmann
U
U
Butzer
G
G
Leder
E
E
Sunelaitis
J
J
Pillasch
D
D
Salonga
K D
KD
Danenberg
P V
PV
Danenberg
H G
HG
Beger
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005492:Folic Acid / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D008942:Mitoxantrone / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013940:Thymidylate Synthase / Q000032:analysis*; D016896:Treatment Outcome; D014410:Tumor Stem Cell Assay
D015251:Epirubicin; D016685:Mitomycin; D005492:Folic Acid; D008942:Mitoxantrone; D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil