title: High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.
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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Kenneth Norris Jr Comprehensive Cancer Center, Los Angeles, CA 90033.
authors.forename: F M
authors.initials: FM
authors.lastname: Muggia
authors.forename: T D
authors.initials: TD
authors.lastname: Brown
authors.forename: P J
authors.initials: PJ
authors.lastname: Goodman
authors.forename: J S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: E M
authors.initials: EM
authors.lastname: Hersh
authors.forename: T R
authors.initials: TR
authors.lastname: Fleming
authors.forename: L
authors.initials: L
authors.lastname: Leichman
mesh_terms: D000328:Adult; D000368:Aged; D001778:Blood Coagulation Disorders / Q000139:chemically induced*; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000188:drug therapy; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000150:complications* / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha