Regional biologic therapy. Hepatic arterial infusion of recombinant human tumor necrosis factor in patients with liver metastases.
Twenty-two chemotherapy-resistant patients with liver metastases received 46 courses of recombinant human tumor necrosis factor (rhTNF) administered by 5-day continuous infusion through percutaneously inserted hepatic arterial catheters. The maximum tolerated daily dose of rhTNF was 150 micrograms/m2. This is six times the maximum tolerated daily dose of rhTNF that could be given systemically (intravenous) on the same schedule. The dose-limiting toxicity resulted in severe, although transient, hypophosphatemia (less than 1.0 mg/dl) associated with myocardial dysfunction. Objective tumor response (partial tumor response or greater) was observed in 2 of 14 patients (14%) with colorectal cancer and lasted as long as 3 months. Three additional minor responses occurred among these patients with colorectal cancer. Plasma carcinoembryonic antigen levels also decreased significantly (greater than 25%) in 7 of the 14 (50%) patients with colorectal cancer. Regional biologic therapy with rhTNF as a sole modality has definite antitumor activity in colorectal cancer metastatic to the liver and warrants additional study in previously untreated patients.
Mavligit
G M
GM
Department of Clinical Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Zukiwski
A A
AA
Charnsangavej
C
C
Carrasco
C H
CH
Wallace
S
S
Gutterman
J U
JU
D000328:Adult; D000368:Aged; D004351:Drug Resistance; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha