A phase I study of intraarterial iododeoxyuridine in patients with colorectal liver metastases.
Regional delivery of iododeoxyuridine (IdUrd) to patients with colorectal liver metastases was examined in a phase I study. The maximum-tolerated intraarterial (IA) dose (MTD) was 1,333 mg/m2/d administered continuously for 14 days. The dose-limiting toxicity was thrombocytopenia. Thrombocytopenia and leukopenia were correlated with the amount of IdUrd incorporated into DNA of peripheral granulocytes. In contrast to our experience with 5-fluorodeoxyuridine, there was no evidence of hepatobiliary toxicity. In 11 patients who received IA IdUrd alone, seven had a greater than or equal to 50% decrease in carcinoembryonic antigen (CEA) levels, with five having tumor volume reductions of 65%, 48%, 46%, 44%, and 27%. Thus, IA IdUrd alone has antitumor efficacy. Patients subsequently received IdUrd in combination with external beam radiation to a total dose of 2,400 cGy without acute local toxicity. In addition to these favorable clinical findings, we have previously shown that IdUrd is selectively incorporated into tumor DNA compared with normal liver in these patients. Further phase II evaluations of this approach are warranted.
Chang
A E
AE
Surgery Branch, National Cancer Institute, Bethesda, Md.
Collins
J M
JM
Speth
P A
PA
Smith
R
R
Rowland
J B
JB
Walton
L
L
Begley
M G
MG
Glatstein
E
E
Kinsella
T J
TJ
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000378:metabolism; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006499:Hepatic Artery; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007065:Idoxuridine