The intrapleural administration of recombinant interleukin-2 (rIL-2) to patients with malignant pleural effusion: clinical trials.
ABSTRACT Recombinant IL-2 (rIL-2) was administered intrapleurally according to an original protocol to 11 patients with malignant pleural effusion, 7 of whom suffered from breast cancer and 4 from esophageal cancer. The pleural effusions either disappeared or decreased roentgenographically, and malignant cells disappeared from all 13 pleural cavities in the 11 patients, confirming the validity of this therapy to be 100%. The mean survival time from the initial administration of rIL-2 was 15.9 months. We ensured that the concentration of IL-2 in the effusion was maintained at a high level for a sufficient period of time, and that the lymphokine-activated killer (LAK) activity of lymphocytes in the effusion was augmented. Fever, eosinophilia, and a transient increase in the pleural effusion were the main side effects, but the symptoms were temporary and not serious. The results of this study therefore suggest the efficacy of intrapleural rIL-2 for patients with malignant pleural effusion.
- [show abstract] [hide abstract]
ABSTRACT: Recombinant interleukin 2 (rIL 2, Cetus) was administered in escalating doses to 30 patients with advanced malignancy, including 14 patients with the epidemic form of Kaposi's sarcoma, in 2 week treatment cycles as a 6 h i.v. infusion for 10 doses. The maximum tolerated dose was 2 X 10(6) U/m2, with dose-limiting toxicity consisting of fever, diarrhea, and thrombocytopenia. At a well-tolerated dose of 1 X 10(6) U/m2, serum levels of rIL 2 of 30 U/ml were maintained for the duration of the infusion. Such concentrations sustain IL 2-dependent T cell growth in vitro. We observed a significant lymphocytosis in patients receiving 1 X 10(6) U/m2 of rIL 2 following 2 weeks of treatment (p = 0.0035). The expanded T cell pool was polyclonal, as demonstrated by increases in both T4+ and T8+ T cell subsets, and activated, with statistically significant increases in IL 2 receptor (p = 0.043), in the absence of transferrin receptor induction. Proliferating cells were not detected in peripheral blood using flow cytometry. Except for alpha-interferon, no other lymphokines (beta- and gamma-interferon, tumor necrosis factor) were present in serum during treatment. Reversible rises in anti-rIL 2 IgG antibodies occurred, as measured using an enzyme-linked immunosorbent assay. No changes were observed in the T cell mitogenic response to OKT3 and phytohemagglutinin, and no enhancement of cytotoxicity against natural killer-sensitive and resistant targets developed as a consequence of treatment. Except for a partial response in a patient with a myelodysplastic syndrome, no antitumor activity was observed. The in vivo expansion of T cells with the capacity to respond to rIL 2 with enhanced in vitro cytotoxicity against tumor targets provides impetus to ongoing trials exploring different routes and schedules of administration of rIL 2.Journal of biological response modifiers 08/1987; 6(4):412-29.
- [show abstract] [hide abstract]
ABSTRACT: Instilled bleomycin and thoracostomy were utilized in 38 patients with malignant pleural effusions; the therapy produced a complete or partial response rate of 63%. Toxicity was minimal. In patients with intraperitoneal effusions, bleomycin instillation after drainage produced a complete or partial response in 36%. One patient had severe hypotension and fever. Patients with ovarian and breast carcinoma responded best, among them, effusions were controlled in greater that 70%. Because of its low systemic toxicity, absence of marrow toxicity, and virtual absence of discomfort, we think that the local instillation of bleomycin is indicated in the management of malignant effusions.Cancer 12/1976; 38(5):1903-8. · 5.20 Impact Factor
- Journal of Thoracic and Cardiovascular Surgery 12/1969; 58(5):758-63. · 3.53 Impact Factor