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A New Syndrome: Ascites, Hyperbilirubinemia, and Hypoalbuminemia after Biochemical Modulation of Fluorouracil with N-Phosphonacetyl-L-Aspartate (PALA)

Nancy Kemeny, MD; Karen Seiter, MD; Daniel Martin, MD; Carlos Urmacher, MD; Donna Niedzwiecki, PhD; Robert C. Kurtz, MD; Patricia Costa, RN; and Margaret Murray, BA
[+] Article, Author, and Disclosure Information

Grant Support: U.S. Bioscience and National Cancer Institute grant PO1-CA-25842.

Requests for Reprints: Nancy Kemeny, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Current Author Addresses: Drs. Kemeny, Seiter, Urmacher, Niedzwiecki, and Kurtz and Ms. Costa and Ms. Murray: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Dr. Martin: Department of Surgery, Catholic Medical Center, 89-15 Woodhaven Boulevard, Queens, NY 11421.

©1991 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1991;115(12):946-951. doi:10.7326/0003-4819-115-12-946
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Objective: To report a new syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia after treatment with N-phosphonacetyl-L-aspartate (PALA) and fluorouracil for metastatic colorectal cancer.

Design: Retrospective analysis.

Setting: Regional cancer treatment center.

Patients: Forty-four previously untreated patients with metastatic colorectal cancer in a phase I-II trial of PALA-fluorouracil.

Measurements and Main Results: One or more transient hepatic abnormalities frequently occurred in 15 of the 17 responding patients. Within the first 10 weeks of treatment, 5 patients developed ascites, 12 had a decrease in the serum albumin level, 6 developed bilirubin elevations, and 7 had transaminase elevations, all in the presence of a complete or partial tumor response. Prolongations of the prothrombin time and elevations of serum glucose levels were also seen.

Conclusions: An unusual syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia is associated with a PALA-fluorouracil regimen. These abnormalities, which may be related to decreased hepatic protein synthesis, occurred more often in patients whose tumor was responding to chemotherapy. Clinicians must recognize that in patients undergoing chemotherapy with these agents, ascites and elevated liver function tests may be secondary to drug administration and are not necessarily due to disease progression.





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