title: Phase I/II dose escalation study of recombinant human interleukin-11 following ifosfamide, carboplatin and etoposide in children, adolescents and young adults with solid tumours or lymphoma: a clinical, haematological and biological study.
abstract: Thrombocytopenia remains the major dose-limiting toxicity of myelosuppressive chemotherapy in children with solid tumours. Recombinant human interleukin-11 (rhIL-11) has been approved by the Food and Drug Administration as treatment for adults with solid tumours and lymphomas with severe chemotherapy-induced thrombocytopenia. We conducted a phase I/II trial of rhIL-11 following ifosfamide, carboplatin and etoposide (ICE) chemotherapy in children with solid tumours or lymphomas. Patients received ifosfamide 1800 mg/m(2)/d for 5 d, carboplatin 400 mg/m(2)/d for 2 d and etoposide 100 mg/m(2)/d for 5 d with rhIL-11 subcutaneous (s.c.) at 25-125 microg/kg/d on days 6-33. Forty-seven patients with median age 10.5 years (range, 0.7-26 years) were studied. Median days to absolute neutrophil count >/=0.5 x 10(9)/l, platelet count >/=50 x 10(9)/l and platelet transfusions were 23, 18, 18, 16.5 and 18.5, 21, 20, 18 and 3, 3, 4, and 2 d at doses 25, 50, 75 and 100 Schulteg/kg respectively. There was a dose-dependent increase in C(max) (7.6-25.5 ng/ml), AUC(0-rho) (57-209 ng.h/ml) and T(1/2) (4-8.2 h) respectively. There was a 4% incidence of anti-IL-11 antibody formation. Clinically important adverse events to rhIL-11 were papilloedema and periosteal bone formation. In summary, rhIL-11 was well tolerated at doses of </=50 microg/kg (maximal tolerated dose) and associated with improved haematological recovery and reduced platelet transfusion requirements compared with historical controls receiving similar ICE chemotherapy without rhIL-11.
authors.affiliation: Department of Pediatrics, Columbia University, New York, NY, USA. mc1310@columbia.edu
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
authors.forename: Virginia
authors.initials: V
authors.lastname: Davenport
authors.forename: Olga
authors.initials: O
authors.lastname: Bessmertny
authors.forename: Stanton C
authors.initials: SC
authors.lastname: Goldman
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Berg
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kreissman
authors.forename: Joseph
authors.initials: J
authors.lastname: Laver
authors.forename: Violet
authors.initials: V
authors.lastname: Shen
authors.forename: Rita
authors.initials: R
authors.lastname: Secola
authors.forename: Carmella
authors.initials: C
authors.lastname: van de Ven
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D017370:Interleukin-11 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D010976:Platelet Count; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000628:therapy*
chemical_list: D017370:Interleukin-11; D011994:Recombinant Proteins; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide