Antipyrine Metabolism during Chemotherapy with 5-Fluorouracil Plus Folinic Acid in Patients with Liver Metastases from Primary Colorectal Cancer.
Current evidence suggests that the drug-metabolizing capacity of the liver can be altered by neoplastic lesions and by the chemotherapeutic agents used to treat them. Antipyrine metabolism is a widely used dynamic test for assessing mixed hepatic oxidase system activity in humans. This study was conducted to determine the effects of 5-fluorouracil-folinic acid chemotherapy on hepatic drug metabolization in patients with diffuse liver metastases from colorectal tumors using antipyrine metabolism as an index. Twenty-three patients, all with diffuse liver metastases from primary colorectal tumors and normal liver function tests, were treated with 5-day cycles of 5-fluorouracil (5-FU) (370 mg m(minus sign2) day(minus sign1) I.V.) and folinic acid (200 mg m(minus sign2) day(minus sign1) I.V.) administered every 28 days. Antipyrine metabolism was assessed before initiation of therapy and after each 5-day cycle to determine the effects of this chemotherapeutic protocol on the mixed-hepatic oxidase system. Response to treatment was assessed after 4 months. None of the patients displayed any change in antipyrine metabolism following treatment. There was no correlation between the ability to metabolize antipyrine and the response to chemotherapy. 5FU has been found to decrease antipyrine metabolism in rats with no liver disease. The absence of such an effect in our patients is thought to be due to inductive effects exerted by the metastases on the mixed hepatic oxidase system and modification of 5-FU metabolism by folinic acid. The liver appears to have an enormous functional reserve, even when there is massive tumor involvement.
Grieco
Antonio
A
Istituto di Clinica Medica Generale e Terapia Medica, Università Cattolica del Sacro Cuore, Rome, Italy.
Castellano
Rosario
R
Matera
Anna
A
Ragazzoni
Enzo
E
Fontana
Tecla
T
Barone
Carlo
C