Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion - Results of a phase II study on 31 consecutive patients

Malignant pleural mesothelioma is often unresectable at diagnosis, is refra ctory to cytotoxic agents and is frequently complicated by pleural effusion . The expected survival range for patients with or without involvement of v isceral pleura is respectively 1-9 and 9-12 months: mesothelioma-related pl eural effusion severely impairs the patients' quality of life and easily re lapses after conservative treatments. Intrapleural administration of IL-2 i s reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic adminis tration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion. we p erformed a phase II study on 31 consecutive patients (M.F 16/15: median age 61 years. range 40 84. PS ECOG 0 n = 7. ECOG 1 n = 15: ECOG 2 n = 9, stage IA, n = 13: IB II = 9: II n = 7; IV = 2) who received first-line therapy w ith intrapleural repeated instillation of 9 000 000 I.U. IL-2 twice-weekly for 4 weeks. after needle thoracenthesis. In nonprogressing patients. 3 000 000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 m onths. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fryer in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in o ne patient (3%): tonicity during subcutaneous treatment was mild to moderat e. mainly a Ru-like syndrome. In 28/31 (90%) of patients there was no furth er or minimal (asymptomatic) pleural fluid collection (according to Paladin e criteria). pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT. occurred in seven pati ents (one CR and six PR: ORR 22%): ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5 39) in all pati ents. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneo usly in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageabl e toxicity. The overall survival observed in nonprogressing patients warran ts further randomized studies with IL-2 aimed to the patient outcome. (C) 2 001 Elsevier Science Ireland Ltd. All rights reserved.