title: Continuous interleukin-2 infusion combined with cyclophosphamide- based combination chemotherapy in the treatment of hemato-oncological malignancies. Results of a phase I-II study.
abstract: 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.
authors.affiliation: Department of Bone Marrow Transplantation and Cancer Immunobiology Research, Hadassah University Hospital, Jerusalem, Israel. nagler@hadassah.org.il
authors.forename: A
authors.initials: A
authors.lastname: Nagler
authors.forename: A
authors.initials: A
authors.lastname: Ackerstein
authors.forename: M
authors.initials: M
authors.lastname: Ben-Shahar
authors.forename: R
authors.initials: R
authors.lastname: Or
authors.forename: E
authors.initials: E
authors.lastname: Naparstek
authors.forename: R
authors.initials: R
authors.lastname: Ben-Yosef
authors.forename: S
authors.initials: S
authors.lastname: Slavin
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000187:drug effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D007938:Leukemia / Q000188:drug therapy* / Q000532:radiotherapy / Q000628:therapy; D008223:Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000628:therapy; D008297:Male; D008875:Middle Aged
chemical_list: D007376:Interleukin-2; D003520:Cyclophosphamide