Intrapleural administration of interleukin-2 for the treatment of patients with malignant pleural mesothelioma: A phase II study

Abstract

BACKGROUND. The prognosis associated with malignant pleural mesothelioma (MPM) is poor in spite of surgery, radiotherapy, photodynamic therapy, or chemotherapy. Therefore, new therapeutic strategies, including intrapleural immunotherapy, are being investigated. Several clinical studies have demonstrated objective antitumoral responses to intrapleural interleukin-2 (IL-2) administration in the treatment of malignant pleurisy. The maximum tolerated dose, 24 x 106 IU/m2/day for 5 days, was determined in a Phase I study. Based on these results, a Phase II study was conducted, in which intrapleural IL-2 (21 x 106 IU/m2/day for 5 days) was given to patients with MPM. METHODS. Patients with histologically documented MPM were evaluated for response 36 days after treatment by computed tomography scan and thoracoscopy with biopsies. Toxicity was recorded and graded according to World Health Organization criteria. Survival was calculated from the start of treatment to death according to the Kaplan-Meier method, and the survival of responders and nonresponders was compared using the log rank test. RESULTS. Twenty-two patients entered this study. Of the 22 cases of MPM, 19 were epithelial, 2 were mixed, and 1 was fibrosarcomatous. Three patients had Stage IA disease, 1 had Stage IB, 16 had Stage II, 1 had Stage III, and 1 had Stage IV (Butchart classification). All patients received their planned treatment. No dose reduction or interruption occurred. There were 11 partial responses and 1 complete response. Stable disease occurred in 3 patients and disease progression in 7 patients. The overall median survival time was 18 months; the median survival time of responders differed significantly from that of nonresponders (28 months vs. 8 months, P < 0.01). The 24- and 36- month survival rates for responders were 58% and 41%, respectively. CONCLUSIONS. These results confirm that intrapleural administration of IL-2 is well tolerated and has antitumor activity in patients with MPM. The authors recommend a dose of 21 x 106 IU/m2/day for 5 days. However, determination of the schedule of IL-2 and its superiority to conventional treatment in a Phase III study has yet to be accomplished.