A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer

• Published in: Cancer chemotherapy and pharmacology 1986-01, Vol.18 (1), p.63-68
• Main Authors: SRISKANDAN, K, GARNER, P, WATKINSON, J, PETTINGALE, K. W, BRINKLEY, D, CALMAN, F. M. B, TEE, D. E. H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Body Weight; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Fatigue - chemically induced; Female; Fever - chemically induced; Humans; Infusions, Intravenous; Interferon-gamma - toxicity; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Neoplasms - therapy; Pharmacology. Drug treatments; Recombinant Proteins - toxicity; Tachycardia - chemically induced
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/BF00253067

Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.