INTRAPLEURAL ADMINISTRATION OF INTERLEUKIN-2 FOR THE TREATMENT OF PATIENTS WITH MALIGNANT PLEURAL MESOTHELIOMA - A PHASE-II STUDY

BACKGROUND. The prognosis associated with malignant pleural mesothelio ma (MPM) is poor in spite of surgery, radiotherapy, photodynamic thera py, or chemotherapy. Therefore, new therapeutic strategies, including intrapleural immunotherapy, are being investigated. Several clinical s tudies have demonstrated objective antitumoral responses to intrapleur al interleukin-2 (IL-2) administration in the treatment of malignant p leurisy. The maximum tolerated dose, 24 x 10(6) IU/m(2)/ day for 5 day s, was determined in a Phase I study. Based on these results, a Phase II study was conducted, in which intrapleural IL-2 (21 x 10(6) IU/m(2) /day for 5 days) was given to patients with MPM. METHODS, Patients wit h histologically documented MPM were evaluated for response 36 days af ter treatment by computed tomography scan and thoracoscopy with biopsi es. Toxicity was recorded and graded according to World Health Organiz ation criteria. Survival was calculated from the start of treatment to death according to the Kaplan-Meier method, and the survival of respo nders and nonresponders was compared using the log rank test. RESULTS. Twenty-two patients entered this study. Of the 22 cases of MPM, 19 we re epithelial, 2 were mixed, and I was fibrosarcomatous. Three patient s had Stage IA disease, I had Stage IB, 16 had Stage II, 1 had Stage I II, and 1 had Stage IV (Butchart classification). All patients receive d their planned treatment. No dose reduction or interruption occurred. There were 11 partial responses and 1 complete response. Stable disea se occurred in 3 patients and disease progression in 7 patients. The o verall median survival time was 18 months; the median survival time of responders differed significantly from that of nonresponders (28 mont hs vs. 8 months, P < 0.01). The 24- and 36-month survival rates for re sponders were 58% and 41%, respectively. CONCLUSIONS. These results co nfirm that intrapleural administration of IL-2 is well tolerated and h as antitumor activity in patients with MPM. The authors recommend a do se of 21 x 10(6) IU/m(2)/day for 5 days. However, determination of the schedule of IL-2 and its superiority to conventional treatment in a P hase III study has yet to be accomplished. Cancer 1998;83:2099-104. (C ) 1998 American Cancer Society.