title: A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy.
abstract: We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.
authors.affiliation: Section of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Gordon
authors.forename: W J
authors.initials: WJ
authors.lastname: McCaskill-Stevens
authors.forename: L A
authors.initials: LA
authors.lastname: Battiato
authors.forename: J
authors.initials: J
authors.lastname: Loewy
authors.forename: D
authors.initials: D
authors.lastname: Loesch
authors.forename: E
authors.initials: E
authors.lastname: Breeden
authors.forename: R
authors.initials: R
authors.lastname: Hoffman
authors.forename: K J
authors.initials: KJ
authors.lastname: Beach
authors.forename: B
authors.initials: B
authors.lastname: Kuca
authors.forename: J
authors.initials: J
authors.lastname: Kaye
authors.forename: G W
authors.initials: GW
authors.lastname: Sledge
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D017370:Interleukin-11 / Q000008:administration & dosage*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000517:prevention & control*
chemical_list: D017370:Interleukin-11; D011994:Recombinant Proteins; C105308:oprelvekin