Sorbitol removal by the metastatic liver: a predictor of systemic toxicity of intra-arterial chemotherapy in patients with liver metastases.
OBJECTIVE
Hepatic arteriovenous shunting in the metastatic liver reduces the advantages of intraarterial infusion of chemotherapeutic agents because of the passage of drugs into the systemic circulation. The aim of this study was to quantitatively assess spontaneous functional hepatic arteriovenous shunting in patients with liver metastases and to determine its implication in the increase in systemic toxic effects of intra-arterial infusion chemotherapy with floxuridine.


METHODS
Twenty-five patients who underwent implantation of arterial ports for regional chemotherapy of liver metastases were studied. Functional hepatic arterio-venous shunting was evaluated through the bioavailability of intra-arterially administered D-sorbitol, a safe, natural compound whose kinetic features make its hepatic clearance flow dependent. In addition, D-sorbitol hepatic clearance (a parameter reflecting functional liver blood flow) and common liver function tests were evaluated for each studied patient. Patients were then grouped with respect to the percentage of medically-assessed liver occupation by metastases and with respect to systemic toxicity of the chemotherapeutic treatment. Both univariate and multivariate analyses by Student's t-test and stepwise logistic regression, respectively, were performed in both groups for each of the evaluated parameters (age, liver function tests, D-sorbitol hepatic clearance and arterial bioavailability).


RESULTS
Arterial bioavailability of D-sorbitol ranged between 0.05 and 0.72 and was significantly greater in patients with more than 50% liver occupation (0.39+/-0.19) compared with those with minor liver involvement (0.17+/-0.13; p = 0.003); it was also significantly greater in patients experiencing high-grade systemic toxicity (0.40+/-0.19) compared with those with low-grade toxicity (0.16+/-0.11; p<0.001). Multivariate analysis showed that arterial bioavailability of D-sorbitol was the only parameter among those evaluated which was able to predict systemic toxicity of this kind of chemotherapy.


CONCLUSIONS
Our results show that, in the metastatic liver, arterial bioavailability of D-sorbitol, an index of functional arteriovenous shunting, varies widely, is significantly greater in patients with massive liver occupation and it is a good predictor of systemic toxicity of intra-arterial regional chemotherapy with floxuridine.
Division of General Medicine A, San Giovanni Battista Hospital, Turin, Italy.
F
F
Bar
S
S
Battista
M C
MC
Bucchi
C
C
Zanon
M
M
Grosso
O
O
Alabiso
S
S
Miraglia
N
N
Cappello
A
A
Gariboldi
G
G
Molino
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001166:Arteriovenous Shunt, Surgical; D001682:Biological Availability; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D013012:Sorbitol / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013012:Sorbitol