A phase I trial of intrapleural recombinant human interferon alpha (rHuIFN alpha 2b) 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 alpha (rHuIFN alpha 2b) was initiated to determine the toxicity and maximal tolerated dose in this group of patients. rHuIFN alpha 2b was instilled as a single dose following chest tube (15/16) or percutaneous (1/16) drainage of cytologically proven malignant effusions. Doses of rHuIFN alpha 2b were escalated from 25 x 10(6) to 200 x 10(6) 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 rHuIFN alpha 2b. Dose-limiting toxicity occurred at 200 x 10(6) 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 rHuIFN alpha 2b should utilize up to 150 x 10(6) U/m2 for intrapleural instillation.