INTERFERON INSTILLATION FOR MALIGNANT PLEURAL EFFUSIONS

Background: Malignant pleural effusions can be managed in various ways including instillation of antineoplastic agents. Instillations of alfa interferon-2b (IFN-alpha2b) have been utilized with success in various loco-regional malignancies suggesting a possible role in management of pleural effusions. This trial was designed to evaluate the tolerability and efficacy of intrapleural IFN-alpha2b instillations in this situation. Patients and methods: Twenty-three patients with cytologically proven malignant pleural effusions were given IFN-alpha2b 50 x 10(6) units in 50 ml normal saline (NS) by intrapleural instillation after partial or complete clearance of effusions by percutaneous aspiration or chest tube drainage. For persistent or recurrent effusions, instillations were repeated with dose escalation to 75 x 10(6) Units. Patients were assessed and monitored by regular clinical examinations, chest radiographs, biochemical and hematological parameters and assays of lymphocyte subpopulations until relapse or death in each case. Results: Fourteen of 20 evaluable patients (70%) had responses lasting for a median of 6 months; there were 8 complete responses (CR) and 6 partial responses (PR). In 6 CR patients the effusions did not recur after the first instillation. In 2 of 6 other patients, the second instillation was successful in inducing CR. Intrapleural instillation of IFN-alpha2b was well tolerated, no grade 4 toxicities were encountered. There were no significant effects on any of the studied parameters at the initial dose level; however, grade 3 neutropenia occurred with the escalated dose. The most common toxicity was flu-like syndrome, after 70% of the instillations. Conclusions: Intrapleural instillation of IFN-alpha2b produced an encouraging response rate without significant toxicities. This approach may warrant additional phase II or phase III comparative clinical studies.