High incidence of coagulopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers

F. M. Muggia, T. D. Brown, P. J. Goodman, J. S. Macdonald, Evan M Hersh, T. R. Fleming, L. Leichman

Research output: Contribution to journalArticle

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Abstract

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 μg intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas. Moreover, rTNF's action in activating the coagulation system and other metabolic effects pose a hazard to patients with adenocarcinoma that may be particularly prone to manifest these changes as part of their illness.

Original languageEnglish (US)
Pages (from-to)211-217
Number of pages7
JournalAnti-Cancer Drugs
Volume3
Issue number3
StatePublished - 1992
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Stomach Neoplasms
Tumor Necrosis Factor-alpha
Incidence
Chills
Hypotension
Stomach
Adenocarcinoma
Fever
Therapeutics
Hypertriglyceridemia
Liver
Myalgia
Enzymes
Neutropenia
Fibrin
Hyperglycemia
Thrombocytopenia
Nausea
Vomiting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

Muggia, F. M., Brown, T. D., Goodman, P. J., Macdonald, J. S., Hersh, E. M., Fleming, T. R., & Leichman, L. (1992). High incidence of coagulopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. Anti-Cancer Drugs, 3(3), 211-217.

High incidence of coagulopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. / Muggia, F. M.; Brown, T. D.; Goodman, P. J.; Macdonald, J. S.; Hersh, Evan M; Fleming, T. R.; Leichman, L.

In: Anti-Cancer Drugs, Vol. 3, No. 3, 1992, p. 211-217.

Research output: Contribution to journalArticle

Muggia, FM, Brown, TD, Goodman, PJ, Macdonald, JS, Hersh, EM, Fleming, TR & Leichman, L 1992, 'High incidence of coagulopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers', Anti-Cancer Drugs, vol. 3, no. 3, pp. 211-217.
Muggia, F. M. ; Brown, T. D. ; Goodman, P. J. ; Macdonald, J. S. ; Hersh, Evan M ; Fleming, T. R. ; Leichman, L. / High incidence of coagulopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. In: Anti-Cancer Drugs. 1992 ; Vol. 3, No. 3. pp. 211-217.
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