Continuous interleukin-2 infusion combined with cyclophosphamide- based combination chemotherapy in the treatment of hemato-oncological malignancies. Results of a phase I-II study.

The combination of a cyclophosphamide (CTX)-based chemotherapy regimen and interleukin-2 (IL-2) has been shown to provide synergistic effects against malignancy in animal models. We therefore conducted a phase I-II trial combining CTX-based combination chemotherapy or CTX alone with high-dose IL-2 in patients with advanced and refractory malignant disease. Fifteen patients with hemato-oncological malignancies (malignant lymphoma 8, multiple myeloma 3, solid tumor 2, leukemia 2) were enrolled in the study. Continuous high-dose IL-2 infusion was shown to be safely administered, starting as soon as recovery of white blood cell count. All patients developed rebound lymphocytosis 24-48 h after termination of IL-2 infusion. Although grade IV toxicity was observed in 5 patients (7 episodes), all side effects completely subsided. Triple chemotherapy (CTX, etoposide and Ara-C) seemed rather toxic (in this group of heavily treated patients) while CTX alone was well tolerated. Four out of 13 (31%) evaluable patients had partial response and another patient (7%) had stabilization of disease progression lasting 2-8 months. Our conclusion is that the combination of CTX and continuous infusion of IL-2 is feasible and should be investigated in patients with various malignant neoplasms.