Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma

Mark H. Einstein, Merieme Klobocista, June Y. Hou, Stephen Lee, Subhakar Mutyala, Keyur J. Mehta, Laura L. Reimers, Dennis Yi-Shin Kuo, Gloria S. Huang, Gary L. Goldberg

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Abstract

Objective: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin "sandwiched" with RT in patients with surgically staged and completely resected uterine carcinosarcoma. Methods: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m 2/day × 5 days) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods. Results: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p = 0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p = 0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively. Conclusions: Ifosfamide "sandwiched" with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile.

Original languageEnglish (US)
Pages (from-to)26-30
Number of pages5
JournalGynecologic Oncology
Volume124
Issue number1
DOIs
StatePublished - Jan 2012

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Carcinosarcoma
Ifosfamide
Cisplatin
Radiation
Radiotherapy
Disease-Free Survival
Brachytherapy
Neutropenia
Thrombocytopenia
Anemia

Keywords

  • Adjuvant therapy
  • Carcinosarcoma
  • Ifosfamide
  • Phase II trial
  • Radiation therapy
  • Uterine cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma. / Einstein, Mark H.; Klobocista, Merieme; Hou, June Y.; Lee, Stephen; Mutyala, Subhakar; Mehta, Keyur J.; Reimers, Laura L.; Kuo, Dennis Yi-Shin; Huang, Gloria S.; Goldberg, Gary L.

In: Gynecologic Oncology, Vol. 124, No. 1, 01.2012, p. 26-30.

Research output: Contribution to journalArticle

Einstein, Mark H. ; Klobocista, Merieme ; Hou, June Y. ; Lee, Stephen ; Mutyala, Subhakar ; Mehta, Keyur J. ; Reimers, Laura L. ; Kuo, Dennis Yi-Shin ; Huang, Gloria S. ; Goldberg, Gary L. / Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma. In: Gynecologic Oncology. 2012 ; Vol. 124, No. 1. pp. 26-30.
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abstract = "Objective: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin {"}sandwiched{"} with RT in patients with surgically staged and completely resected uterine carcinosarcoma. Methods: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m 2/day × 5 days) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods. Results: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p = 0.16), so they were combined for analysis. 19 patients (70{\%}) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p = 0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18{\%}, 4{\%} and 4{\%} of cycles, respectively. Conclusions: Ifosfamide {"}sandwiched{"} with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile.",
keywords = "Adjuvant therapy, Carcinosarcoma, Ifosfamide, Phase II trial, Radiation therapy, Uterine cancer",
author = "Einstein, {Mark H.} and Merieme Klobocista and Hou, {June Y.} and Stephen Lee and Subhakar Mutyala and Mehta, {Keyur J.} and Reimers, {Laura L.} and Kuo, {Dennis Yi-Shin} and Huang, {Gloria S.} and Goldberg, {Gary L.}",
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T1 - Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma

AU - Einstein, Mark H.

AU - Klobocista, Merieme

AU - Hou, June Y.

AU - Lee, Stephen

AU - Mutyala, Subhakar

AU - Mehta, Keyur J.

AU - Reimers, Laura L.

AU - Kuo, Dennis Yi-Shin

AU - Huang, Gloria S.

AU - Goldberg, Gary L.

PY - 2012/1

Y1 - 2012/1

N2 - Objective: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin "sandwiched" with RT in patients with surgically staged and completely resected uterine carcinosarcoma. Methods: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m 2/day × 5 days) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods. Results: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p = 0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p = 0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively. Conclusions: Ifosfamide "sandwiched" with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile.

AB - Objective: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin "sandwiched" with RT in patients with surgically staged and completely resected uterine carcinosarcoma. Methods: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m 2/day × 5 days) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m 2/day × 5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods. Results: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p = 0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p = 0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively. Conclusions: Ifosfamide "sandwiched" with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile.

KW - Adjuvant therapy

KW - Carcinosarcoma

KW - Ifosfamide

KW - Phase II trial

KW - Radiation therapy

KW - Uterine cancer

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