An experimental study on the pharmacokinetics of 5-fluorouracil regional chemotherapy for pancreatic cancer.

Abstract

BACKGROUND:

Recently a few centers reported promising results of regional intra-arterial chemotherapy for pancreatic cancer. However, the detailed pharmacokinetics and the side effects of anticancer agents remain unclear.

METHODS:

Catheters were introduced into the gastroduodenal artery and the splenic artery of dogs. In group I, arterial infusion of 5-fluorouracil (5-FU) was performed over 10 minutes. In group II, 5-FU was infused systemically. In group III, an intra-arterial infusion was repeated weekly three times. Blood samples and liver and pancreas tissue samples were obtained to determine 5-FU levels. In a subset of each group, the pancreas, duodenum, and liver were excised for histological analyses.

RESULTS:

Immediately after the infusion of 5-FU, the portal level in group I was higher than that in group II. However, the mean systemic level in group I was lower than in group II. The mean tissue concentration in the pancreas in group I was significantly higher than that of group II. Histological examination revealed no microscopic alterations after treatment in all groups, including group III.

CONCLUSIONS:

This fundamental study suggested that intra-arterial chemotherapy of 5-FU for pancreatic cancer allows higher regional drug delivery without adverse effects on normal regions of the pancreas, the duodenum, and the liver.

• Authors: Masaaki Mitsutsuji, Yasuyuki Suzuki, Yasuhiro Iwanaga, Yasuhiro Fujino, Yasuki Tanioka, Takashi Kamigaki, Yonson Ku, Yoshikazu Kuroda
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 10 Issue 5 Pg. 546-50 (Jun 2003) ISSN: 1068-9265 [Print] United States
• PMID: 12794021 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, pharmacokinetics)
• Dogs
• Duodenum (drug effects)
• Female
• Fluorouracil (administration & dosage, adverse effects, pharmacokinetics)
• Infusions, Intra-Arterial
• Liver (drug effects)
• Male
• Neoplasms, Experimental
• Pancreatic Neoplasms (drug therapy, veterinary)