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.
AuthorsG M Mavligit, A A Zukiwski, C Charnsangavej, C H Carrasco, S Wallace, J U Gutterman
JournalCancer (Cancer) Vol. 69 Issue 2 Pg. 557-61 (Jan 15 1992) ISSN: 0008-543X [Print] UNITED STATES
PMID1728386 (Publication Type: Journal Article)
Chemical References
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Adult
  • Aged
  • Drug Resistance
  • Female
  • Hepatic Artery
  • Humans
  • Infusions, Intra-Arterial
  • Liver Neoplasms (drug therapy, secondary)
  • Male
  • Middle Aged
  • Recombinant Proteins (administration & dosage, adverse effects, therapeutic use)
  • Remission Induction
  • Tumor Necrosis Factor-alpha (administration & dosage, adverse effects, therapeutic use)

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