A phase I trial of intrapleural recombinant human interferon α (rHuIFNα2b) in patients with malignant pleural effusions

The use of intrapleural sclerosing agents to control reaccumulation of pleural fluid in patients with malignant effusions has been widely investigated. A phase I trial of intrapleural recombinant human interferon α (rHuIFNα2b) was initiated to determine the toxicity and maximal tolerated dose in this group of patients. rHuIFNα2b was instilled as a single dose following chest tube (15/16) or percutaneous (1/16) drainage of cytologically proven malignant effusions. Doses of rHuIFNα2b were escalated from 25×106 to 200×106 U/m2 in cohorts of three to four patients. Toxicity was mild to moderate, and included chills, fever and chest pain, and resembled that produced by systemic administration of rHuIFNα2b. Dose-limiting toxicity occurred at 200×106 U/m2 and consisted of hepatic enzyme elevations and renal failure. Partial control of the effusions was noted in two patients, with two additional patients having stable disease. Phase II trials of rHuIFNα2b should utilize up to 150×106 U/m2 for intrapleural instillation.