Adjuvant Pelvic Radiation "sandwiched" between Paclitaxel/Carboplatin Chemotherapy in Women with Completely Resected Uterine Serous Carcinoma: Long-term Follow-up of a Prospective Phase 2 Trial

Marina Frimer, Eirwen M. Miller, Shankar Viswanathan, Eugenia Girda, Keyur J. Mehta, Harriet O. Smith, Dennis Yi-Shin Kuo, Gary L. Goldberg, Mark H. Einstein

Research output: Contribution to journalArticle

Abstract

Objective We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation "sandwiched" between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival. Methods Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m2 and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities. Results One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles. Conclusions The long-term follow-up in this study demonstrates that "sandwich" therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal "sandwich" therapy should be considered in all USC patients who have undergone complete surgical resection and staging.

Original languageEnglish (US)
Pages (from-to)1781-1788
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume28
Issue number9
DOIs
StatePublished - Nov 1 2018

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Carboplatin
Paclitaxel
Radiation
Carcinoma
Drug Therapy
Survival
Area Under Curve
Radiotherapy
National Cancer Institute (U.S.)
African Americans
Disease-Free Survival
Therapeutics
Safety

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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Adjuvant Pelvic Radiation "sandwiched" between Paclitaxel/Carboplatin Chemotherapy in Women with Completely Resected Uterine Serous Carcinoma : Long-term Follow-up of a Prospective Phase 2 Trial. / Frimer, Marina; Miller, Eirwen M.; Viswanathan, Shankar; Girda, Eugenia; Mehta, Keyur J.; Smith, Harriet O.; Kuo, Dennis Yi-Shin; Goldberg, Gary L.; Einstein, Mark H.

In: International Journal of Gynecological Cancer, Vol. 28, No. 9, 01.11.2018, p. 1781-1788.

Research output: Contribution to journalArticle

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title = "Adjuvant Pelvic Radiation {"}sandwiched{"} between Paclitaxel/Carboplatin Chemotherapy in Women with Completely Resected Uterine Serous Carcinoma: Long-term Follow-up of a Prospective Phase 2 Trial",
abstract = "Objective We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation {"}sandwiched{"} between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival. Methods Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m2 and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities. Results One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81{\%}) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22{\%} and 14{\%} of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9{\%} of cycles. Conclusions The long-term follow-up in this study demonstrates that {"}sandwich{"} therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal {"}sandwich{"} therapy should be considered in all USC patients who have undergone complete surgical resection and staging.",
author = "Marina Frimer and Miller, {Eirwen M.} and Shankar Viswanathan and Eugenia Girda and Mehta, {Keyur J.} and Smith, {Harriet O.} and Kuo, {Dennis Yi-Shin} and Goldberg, {Gary L.} and Einstein, {Mark H.}",
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T1 - Adjuvant Pelvic Radiation "sandwiched" between Paclitaxel/Carboplatin Chemotherapy in Women with Completely Resected Uterine Serous Carcinoma

T2 - Long-term Follow-up of a Prospective Phase 2 Trial

AU - Frimer, Marina

AU - Miller, Eirwen M.

AU - Viswanathan, Shankar

AU - Girda, Eugenia

AU - Mehta, Keyur J.

AU - Smith, Harriet O.

AU - Kuo, Dennis Yi-Shin

AU - Goldberg, Gary L.

AU - Einstein, Mark H.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Objective We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation "sandwiched" between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival. Methods Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m2 and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities. Results One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles. Conclusions The long-term follow-up in this study demonstrates that "sandwich" therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal "sandwich" therapy should be considered in all USC patients who have undergone complete surgical resection and staging.

AB - Objective We prospectively evaluated patients with completely resected uterine serous carcinoma (USC) treated with radiation "sandwiched" between carboplatin/paclitaxel (C/T). The primary objective was to determine the safety profile, and the secondary outcome was to evaluate progression-free and overall survival. Methods Surgically staged patients with completely resected USC were enrolled to receive 3 cycles of paclitaxel 175 mg/m2 and carboplatin (area under the curve, 6-7.5) every 21 days, followed by radiotherapy and an additional 3 cycles of T/C at area under the curve of 5-6 (6 cycles + radiotherapy). Toxicity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.03. Kaplan-Meier and log-rank tests were used to compare survival probabilities. Results One hundred forty patients were enrolled, of which 132 were evaluable, completed at least 3 cycles of chemotherapy and radiation. One hundred seven (81%) completed 6 cycles of chemotherapy and radiation. Patients with early-stage (I/II) disease have survival probabilities of 0.96 and 0.81 at 2 and 5 years. Patients with stage I USC and lymphovascular invasion have considerably worse overall survival, with 2.7 times' higher risk of death than those without lymphovascular invasion. Patients with late-stage (III/IV) disease had overall survival probabilities of 0.64 and 0.18 at 2 and 5 years, which is far higher survival than what has been reported in single-modality trials. Interestingly, and different than what is reported in other studies, there is no difference in survival in African Americans versus whites/other races who were evaluable. Of the 779 cycles administered, 22% and 14% of cycles were associated with grades 3 and 4 hematologic toxicities, respectively. Grades 3 and 4 nonhematologic toxicities occurred in 6.9% of cycles. Conclusions The long-term follow-up in this study demonstrates that "sandwich" therapy is an efficacious, well-tolerated treatment approach with acceptable toxicities. Lymphovascular invasion (LVSI) is a significantly poor prognostic factor in stage I USC. Multimodal "sandwich" therapy should be considered in all USC patients who have undergone complete surgical resection and staging.

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