Phase II studies of recombinant human tumor necrosis factor alpha in patients with malignant disease: a summary of the Southwest Oncology Group experience.

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 (rhuTNF alpha) 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 micrograms/m2 of rhuTNF alpha 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, rhuTNF alpha does not appear to have significant antitumor activity. The biological basis for this finding is discussed.