Phase II studies of recombinant human tumor necrosis factor alpha in patients with malignant disease: A summary of the southwest oncology group experience

Evan M. Hersh, Barbara S. Metch, Franco M. Muggia, Thomas D. Brown, Robert P. Whitehead, George T. Budd, John J. Rinehart, E. David Crawford, John D. Bonnet, Brent C. Behrens

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Abstract

From June 1988 to November 1990 the Southwest Oncology Group initiated nine protocols for the phase II evaluation of recombinant human tumor necrosis factor alpha (rhuTNFα) in cancer patients. Patients with diverse metastatic malignancies including breast, colon, gastric, pancreatic, endometrial, and bladder cancers, as well as multiple myeloma and various sarcomas received 150 μg/m2 of rhuTNFa daily for 5 days every other week. Of 147 patients entered in the study, 127 were eligible and were evaluated for toxicity and response. Of 124 patients known to have completed treatment, 92 (74%) went off study for progression, 21 (17%) for toxicity, and 12 (10%) for other causes, mainly that of worsening medical condition. Thirteen percent of patients experienced grade 4 or fatal toxicity. The most serious toxicities were pulmonary failure and coagulopathies. The predominant grade 3 toxicities were symptomatic (chills, fever, malaise, headache, myalgia, and nausea or vomiting). Only one partial remission was seen in a patient with metastatic bladder cancer lasting 4 months (rate 0.8%, exact 95%; confidence interval 0-4%). At the study dose and schedule, rhuTNFαdoes not appear to have significant antitumor activity. The biological basis for this finding is discussed.

Original languageEnglish (US)
Pages (from-to)426-431
Number of pages6
JournalJournal of Immunotherapy
Volume10
Issue number6
DOIs
StatePublished - Dec 1991

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Keywords

  • Antitumor activity
  • Metastatic malignancy
  • Multiple myeloma
  • Recombinant human tumor necrosis factor alpha
  • Sarcoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Hersh, E. M., Metch, B. S., Muggia, F. M., Brown, T. D., Whitehead, R. P., Budd, G. T., Rinehart, J. J., Crawford, E. D., Bonnet, J. D., & Behrens, B. C. (1991). Phase II studies of recombinant human tumor necrosis factor alpha in patients with malignant disease: A summary of the southwest oncology group experience. Journal of Immunotherapy, 10(6), 426-431. https://doi.org/10.1097/00002371-199112000-00006