Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: Final survival results of a SWOG (S0200) phase 3 randomized trial

Maurie Markman, James Moon, Sharon Wilczynski, Ana Maria Lopez, Kendrith M. Rowland, David P. Michelin, Victor J. Lanzotti, Garnet L. Anderson, David S Alberts

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Objectives: Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods: To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results: In the limited number of patients (n = 61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p = 0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p = 0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p = 0.0008), with 5 being > grade 2 in severity. Conclusion: Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions.

Original languageEnglish (US)
Pages (from-to)323-325
Number of pages3
JournalGynecologic Oncology
Volume116
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Carboplatin
Ovarian Neoplasms
Survival
Hypersensitivity
Platinum
Disease-Free Survival
Area Under Curve
Clinical Trials Data Monitoring Committees
liposomal doxorubicin
Appointments and Schedules
Safety
Incidence
Pharmaceutical Preparations

Keywords

  • Carboplatin
  • Ovarian cancer
  • Pegylated liposomal doxorubicin (PLD)
  • Phase 3 Trial

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer : Final survival results of a SWOG (S0200) phase 3 randomized trial. / Markman, Maurie; Moon, James; Wilczynski, Sharon; Lopez, Ana Maria; Rowland, Kendrith M.; Michelin, David P.; Lanzotti, Victor J.; Anderson, Garnet L.; Alberts, David S.

In: Gynecologic Oncology, Vol. 116, No. 3, 03.2010, p. 323-325.

Research output: Contribution to journalArticle

Markman, Maurie ; Moon, James ; Wilczynski, Sharon ; Lopez, Ana Maria ; Rowland, Kendrith M. ; Michelin, David P. ; Lanzotti, Victor J. ; Anderson, Garnet L. ; Alberts, David S. / Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer : Final survival results of a SWOG (S0200) phase 3 randomized trial. In: Gynecologic Oncology. 2010 ; Vol. 116, No. 3. pp. 323-325.
@article{c545ae8fd3994217988576f56b656932,
title = "Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: Final survival results of a SWOG (S0200) phase 3 randomized trial",
abstract = "Objectives: Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods: To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results: In the limited number of patients (n = 61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p = 0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p = 0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30{\%}) of women randomized to single agent carboplatin experienced an allergic episode (p = 0.0008), with 5 being > grade 2 in severity. Conclusion: Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions.",
keywords = "Carboplatin, Ovarian cancer, Pegylated liposomal doxorubicin (PLD), Phase 3 Trial",
author = "Maurie Markman and James Moon and Sharon Wilczynski and Lopez, {Ana Maria} and Rowland, {Kendrith M.} and Michelin, {David P.} and Lanzotti, {Victor J.} and Anderson, {Garnet L.} and Alberts, {David S}",
year = "2010",
month = "3",
doi = "10.1016/j.ygyno.2009.11.026",
language = "English (US)",
volume = "116",
pages = "323--325",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer

T2 - Final survival results of a SWOG (S0200) phase 3 randomized trial

AU - Markman, Maurie

AU - Moon, James

AU - Wilczynski, Sharon

AU - Lopez, Ana Maria

AU - Rowland, Kendrith M.

AU - Michelin, David P.

AU - Lanzotti, Victor J.

AU - Anderson, Garnet L.

AU - Alberts, David S

PY - 2010/3

Y1 - 2010/3

N2 - Objectives: Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods: To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results: In the limited number of patients (n = 61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p = 0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p = 0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p = 0.0008), with 5 being > grade 2 in severity. Conclusion: Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions.

AB - Objectives: Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods: To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results: In the limited number of patients (n = 61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p = 0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p = 0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p = 0.0008), with 5 being > grade 2 in severity. Conclusion: Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions.

KW - Carboplatin

KW - Ovarian cancer

KW - Pegylated liposomal doxorubicin (PLD)

KW - Phase 3 Trial

UR - http://www.scopus.com/inward/record.url?scp=75749110481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75749110481&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2009.11.026

DO - 10.1016/j.ygyno.2009.11.026

M3 - Article

C2 - 20044128

AN - SCOPUS:75749110481

VL - 116

SP - 323

EP - 325

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 3

ER -