TY - JOUR
T1 - Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas
T2 - Results from a prospectively designed analysis of progression-free survival
AU - Alberts, David S.
AU - Marth, Christian
AU - Alvarez, Ronald D.
AU - Johnson, Gary
AU - Bidzinski, Mariusz
AU - Kardatzke, David R.
AU - Bradford, Williamson Z.
AU - Loutit, Jeff
AU - Kirn, David H.
AU - Clouser, Mary C.
AU - Markman, Maurie
PY - 2008/5/1
Y1 - 2008/5/1
N2 - Objectives: Interferon gamma (IFN-γ) is a pleiotropic cytokine with antiproliferative, immunostimulatory, and chemosensitization properties. This trial was designed to evaluate IFN-γ 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer (OC) and primary peritoneal carcinoma (PPC) patients. Methods: Eligible patients were randomized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-γ 1b (100 μg 3×/wk subcutaneously). The primary endpoint was overall survival (OS) time (target hazard ratio (HR) = 0.77). Secondary endpoints included progression-free survival (target HR = 0.7), based on blinded review of serial imaging scans, physical exams, and CA-125 levels. Results: 847 patients were enrolled (OC 774, PPC 73) in Europe (n = 539) and North/South America (n = 308) from January 29, 2002 to March 31, 2004 and stratified according to: optimal debulking (n = 271) versus suboptimal debulking with plans for interval debulking (PID) (n = 238) or no PID (n = 338). The study stopped early following a protocol-defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-γ 1b plus chemotherapy compared to chemotherapy alone (1138 days vs. not estimable, HR = 1.45, 95% CI = 1.15-1.83). At the time of the analysis, 169 of 426 (39.7%) patients in the IFN-γ 1b plus chemotherapy group had died compared to 128 of 421 (30.4%) in the chemotherapy alone group. Serious adverse events were more common in the IFN-γ 1b plus chemotherapy group (48.5% vs. 35.4%), primarily due to a higher incidence of serious hematological toxicities (34.5% vs. 22.7%). Conclusions: Treatment with IFN-γ 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer.
AB - Objectives: Interferon gamma (IFN-γ) is a pleiotropic cytokine with antiproliferative, immunostimulatory, and chemosensitization properties. This trial was designed to evaluate IFN-γ 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer (OC) and primary peritoneal carcinoma (PPC) patients. Methods: Eligible patients were randomized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-γ 1b (100 μg 3×/wk subcutaneously). The primary endpoint was overall survival (OS) time (target hazard ratio (HR) = 0.77). Secondary endpoints included progression-free survival (target HR = 0.7), based on blinded review of serial imaging scans, physical exams, and CA-125 levels. Results: 847 patients were enrolled (OC 774, PPC 73) in Europe (n = 539) and North/South America (n = 308) from January 29, 2002 to March 31, 2004 and stratified according to: optimal debulking (n = 271) versus suboptimal debulking with plans for interval debulking (PID) (n = 238) or no PID (n = 338). The study stopped early following a protocol-defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-γ 1b plus chemotherapy compared to chemotherapy alone (1138 days vs. not estimable, HR = 1.45, 95% CI = 1.15-1.83). At the time of the analysis, 169 of 426 (39.7%) patients in the IFN-γ 1b plus chemotherapy group had died compared to 128 of 421 (30.4%) in the chemotherapy alone group. Serious adverse events were more common in the IFN-γ 1b plus chemotherapy group (48.5% vs. 35.4%), primarily due to a higher incidence of serious hematological toxicities (34.5% vs. 22.7%). Conclusions: Treatment with IFN-γ 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer.
KW - Advanced ovarian
KW - Carboplatin
KW - First-line treatment
KW - Interferon γ-1b
KW - Paclitaxil
KW - Primary peritoneal carcinomas
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U2 - 10.1016/j.ygyno.2008.01.005
DO - 10.1016/j.ygyno.2008.01.005
M3 - Article
C2 - 18314182
AN - SCOPUS:42749083267
VL - 109
SP - 174
EP - 181
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 2
ER -