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: Results from a prospectively designed analysis of progression-free survival

David S Alberts, Christian Marth, Ronald D. Alvarez, Gary Johnson, Mariusz Bidzinski, David R. Kardatzke, Williamson Z. Bradford, Jeff Loutit, David H. Kirn, Mary C. Clouser, Maurie Markman

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)174-181
Number of pages8
JournalGynecologic Oncology
Volume109
Issue number2
DOIs
StatePublished - May 2008

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Carboplatin
Paclitaxel
Disease-Free Survival
Carcinoma
Drug Therapy
Ovarian Neoplasms
Therapeutics
Survival
South America
North America
Interferon-gamma
interferon gamma-1b
Cytokines
Incidence

Keywords

  • Advanced ovarian
  • Carboplatin
  • First-line treatment
  • Interferon γ-1b
  • Paclitaxil
  • Primary peritoneal carcinomas

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

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 : Results from a prospectively designed analysis of progression-free survival. / Alberts, David S; Marth, Christian; Alvarez, Ronald D.; Johnson, Gary; Bidzinski, Mariusz; Kardatzke, David R.; Bradford, Williamson Z.; Loutit, Jeff; Kirn, David H.; Clouser, Mary C.; Markman, Maurie.

In: Gynecologic Oncology, Vol. 109, No. 2, 05.2008, p. 174-181.

Research output: Contribution to journalArticle

Alberts, David S ; Marth, Christian ; Alvarez, Ronald D. ; Johnson, Gary ; Bidzinski, Mariusz ; Kardatzke, David R. ; Bradford, Williamson Z. ; Loutit, Jeff ; Kirn, David H. ; Clouser, Mary C. ; Markman, Maurie. / 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 : Results from a prospectively designed analysis of progression-free survival. In: Gynecologic Oncology. 2008 ; Vol. 109, No. 2. pp. 174-181.
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abstract = "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.",
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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

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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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