TY - JOUR
T1 - A phase I trial of cyclosphosphamide and carboplatinum combined with interleukin-3 in women with advanced-stage ovarian cancer
AU - Speyer, James L.
AU - Mandeli, John
AU - Hochster, Howard
AU - Runowicz, Carolyn
AU - Wadler, Scott
AU - Wallach, Robert
AU - Cohen, Carmel
AU - Oette, Dagmar
AU - Sorich, Joan
AU - Demakos, Erin
AU - Gelpke, Laura
AU - Goldberg, Gary
AU - Bruckner, Howard
AU - Holland, James
PY - 1995/3
Y1 - 1995/3
N2 - The hematopoietic growth factor, recombinant human interleukin-3 (rhu IL-3), stimulates production of both leukocytes and platelets, and thus potentially has greater utility than growth factors that solely stimulate leukocyte production when employed with dose-intensive chemotherapeutic regimens. To determine the optimal schedule for administration of rhu IL-3 in combination with cyclophosphamide and carboplatin, an aggressive regimen for the treatment of advanced ovarian cancer, a phase I trial was initiated by the New York Gynecologic Oncology Group. Following surgical debulking, all patients received cyclophosphamide and carboplatin for 6 cycles. rhu IL-3 was administered at 50, 250, or 500 μg subcutaneously for 5 days either immediately prior to or after administration of chemotherapy. Cohorts of six patients were treated at each dose level (three pre- and three postchemotherapy). Eighteen patients received 91 cycles of treatment. The major toxicities attributable to rhu IL-3 included fevers, chills, malaise, nausea, and headache, but were not dose-limiting at the doses of rhu IL-3 employed. The major finding of this study was that rhu IL-3 administered after chemotherapy offered greater platelet protection than rhu IL-3 administered prior to chemotherapy as assessed by median platelet nadir and duration of platelet counts <50,000/mm3. A second major finding was a dose-response relationship for rhu IL-3: the two higher doses employed, 250 and 500 μ, offered more effective platelet protection than the lower dose employed, 50 μ. rhu IL-3 had no significant effects on leukocyte nadirs or duration of nadirs at any schedule or dose employed. rhu IL-3 may reduce the thrombocytopenia associated with aggressive treatment with cyclophosphamide and carboplatin, although this remains to be confirmed in a randomized, placebo-controlled trial. The effects of rhu IL-3 are dose- and schedule-dependent.
AB - The hematopoietic growth factor, recombinant human interleukin-3 (rhu IL-3), stimulates production of both leukocytes and platelets, and thus potentially has greater utility than growth factors that solely stimulate leukocyte production when employed with dose-intensive chemotherapeutic regimens. To determine the optimal schedule for administration of rhu IL-3 in combination with cyclophosphamide and carboplatin, an aggressive regimen for the treatment of advanced ovarian cancer, a phase I trial was initiated by the New York Gynecologic Oncology Group. Following surgical debulking, all patients received cyclophosphamide and carboplatin for 6 cycles. rhu IL-3 was administered at 50, 250, or 500 μg subcutaneously for 5 days either immediately prior to or after administration of chemotherapy. Cohorts of six patients were treated at each dose level (three pre- and three postchemotherapy). Eighteen patients received 91 cycles of treatment. The major toxicities attributable to rhu IL-3 included fevers, chills, malaise, nausea, and headache, but were not dose-limiting at the doses of rhu IL-3 employed. The major finding of this study was that rhu IL-3 administered after chemotherapy offered greater platelet protection than rhu IL-3 administered prior to chemotherapy as assessed by median platelet nadir and duration of platelet counts <50,000/mm3. A second major finding was a dose-response relationship for rhu IL-3: the two higher doses employed, 250 and 500 μ, offered more effective platelet protection than the lower dose employed, 50 μ. rhu IL-3 had no significant effects on leukocyte nadirs or duration of nadirs at any schedule or dose employed. rhu IL-3 may reduce the thrombocytopenia associated with aggressive treatment with cyclophosphamide and carboplatin, although this remains to be confirmed in a randomized, placebo-controlled trial. The effects of rhu IL-3 are dose- and schedule-dependent.
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U2 - 10.1006/gyno.1995.1068
DO - 10.1006/gyno.1995.1068
M3 - Article
C2 - 7705673
AN - SCOPUS:0028954011
SN - 0090-8258
VL - 56
SP - 387
EP - 394
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -