Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: A Gynecologic Oncology Group study

Harry J. Long, Brian N. Bundy, Edward C. Grendys, Jo Ann Benda, D. Scott McMeekin, Joel Sorosky, David S. Miller, Lynne A. Eaton, James V. Fiorica, Denise Mackey

Research output: Contribution to journalArticle

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Abstract

Purpose: On the basis of reported activity of methotrexate, vinblastine, doxorubicm, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. Patients and Methods: Eligible patients were randomly allocated to receive cisplatin 50 mg/m2 every 3 weeks (CPT); cisplatin 50 mg/m2 day 1 plus topotecan 0.75 mg/m2 days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m 2 day 2, and cisplatin 70 mg/m2 day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. Results: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. Conclusion: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Original languageEnglish (US)
Pages (from-to)4626-4633
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number21
DOIs
StatePublished - 2005

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Topotecan
Cervix Uteri
Cisplatin
Carcinoma
Vinblastine
Methotrexate
Survival
Uterine Cervical Neoplasms
Disease-Free Survival
Clinical Trials Data Monitoring Committees
Quality of Life
Combination Drug Therapy
Doxorubicin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix : A Gynecologic Oncology Group study. / Long, Harry J.; Bundy, Brian N.; Grendys, Edward C.; Benda, Jo Ann; McMeekin, D. Scott; Sorosky, Joel; Miller, David S.; Eaton, Lynne A.; Fiorica, James V.; Mackey, Denise.

In: Journal of Clinical Oncology, Vol. 23, No. 21, 2005, p. 4626-4633.

Research output: Contribution to journalArticle

Long, HJ, Bundy, BN, Grendys, EC, Benda, JA, McMeekin, DS, Sorosky, J, Miller, DS, Eaton, LA, Fiorica, JV & Mackey, D 2005, 'Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: A Gynecologic Oncology Group study', Journal of Clinical Oncology, vol. 23, no. 21, pp. 4626-4633. https://doi.org/10.1200/JCO.2005.10.021
Long, Harry J. ; Bundy, Brian N. ; Grendys, Edward C. ; Benda, Jo Ann ; McMeekin, D. Scott ; Sorosky, Joel ; Miller, David S. ; Eaton, Lynne A. ; Fiorica, James V. ; Mackey, Denise. / Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix : A Gynecologic Oncology Group study. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 21. pp. 4626-4633.
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abstract = "Purpose: On the basis of reported activity of methotrexate, vinblastine, doxorubicm, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. Patients and Methods: Eligible patients were randomly allocated to receive cisplatin 50 mg/m2 every 3 weeks (CPT); cisplatin 50 mg/m2 day 1 plus topotecan 0.75 mg/m2 days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m 2 day 2, and cisplatin 70 mg/m2 day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. Results: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27{\%} and 13{\%}, respectively. Conclusion: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.",
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T1 - Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix

T2 - A Gynecologic Oncology Group study

AU - Long, Harry J.

AU - Bundy, Brian N.

AU - Grendys, Edward C.

AU - Benda, Jo Ann

AU - McMeekin, D. Scott

AU - Sorosky, Joel

AU - Miller, David S.

AU - Eaton, Lynne A.

AU - Fiorica, James V.

AU - Mackey, Denise

PY - 2005

Y1 - 2005

N2 - Purpose: On the basis of reported activity of methotrexate, vinblastine, doxorubicm, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. Patients and Methods: Eligible patients were randomly allocated to receive cisplatin 50 mg/m2 every 3 weeks (CPT); cisplatin 50 mg/m2 day 1 plus topotecan 0.75 mg/m2 days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m 2 day 2, and cisplatin 70 mg/m2 day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. Results: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. Conclusion: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

AB - Purpose: On the basis of reported activity of methotrexate, vinblastine, doxorubicm, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. Patients and Methods: Eligible patients were randomly allocated to receive cisplatin 50 mg/m2 every 3 weeks (CPT); cisplatin 50 mg/m2 day 1 plus topotecan 0.75 mg/m2 days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m 2 day 2, and cisplatin 70 mg/m2 day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. Results: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. Conclusion: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

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