Phase III Trial of Ifosfamide With or Without Paclitaxel in Advanced Uterine Carcinosarcoma: A Gynecologic Oncology Group Study

Homesley, Howard D.; Filiaci, Virginia L.; Markman, Maurie; Bitterman, Pincas; Eaton, Lynne; Kilgore, Larry C.; Monk, Bradley J.; Ueland, Frederick R.

doi:10.1200/jco.2006.06.4907

Cited by 242 publications

(157 citation statements)

References 15 publications

(11 reference statements)

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“…However, responses to present-day adjuvant radiotherapy and chemotherapy are poor and clinical trials are conducted to improve prognosis by new treatment strategies. Treatment with adjuvant combined chemotherapy seems the most promising compared with single-agent chemotherapy 14,15 or radiotherapy. 16 However, more research is needed to develop the most effective treatment for patients with uterine carcinosarcomas.…”

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confidence: 99%

Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

et al. 2011

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Carcinosarcomas (malignant mixed Mü llerian tumors) of the uterus are rare and aggressive malignancies consisting of an epithelial (carcinoma) and a mesenchymal (sarcoma) tumor component and are considered as metaplastic endometrial carcinomas. This study evaluated molecular characteristics and clinical behavior of uterine carcinosarcomas to improve treatment regimens in the future. Immunohistochemical expression of estrogen receptor-a and -b, progesterone receptor-A and -B, MLH1, MSH2, MSH6, PTEN (phosphatase and tensin homolog deleted on chromosome 10), p53, b-catenin and cyclin D1 was determined in 40 uterine carcinosarcomas. Immunostaining was compared between epithelial and mesenchymal tumor components. To determine the prognostic role of the epithelial component, clinicopathological data and survival were compared between patients with endometrioid and non-endometrioid epithelial tumor components. To determine prognosis of carcinosarcomas compared with high-risk endometrial carcinomas, clinicopathological characteristics and survival were compared between these patients. Hormone receptor expression occurred infrequently: estrogen receptor-a (8%) and -b (32%), progesterone receptor-A (0%) and -B (23%), next to b-catenin (4%) and cyclin D1 (7%). PTEN, MLH1, MSH2 and MSH6 mutations occurred in 39%, 33%, 22% and 21%, respectively (based on absent immunostaining). Overexpression of p53 was observed in 38%. Expression patterns of p53, MSH2 and MSH6 corresponded between epithelial and mesenchymal tumor components. In our cohort, the epithelial component caused the majority of metastases (72%) and vascular invasion (70%). Survival tended to be worse for patients with a non-endometrioid epithelial component compared with an endometrioid epithelial component (5-year survival: 26% and 55%, respectively). Survival was worse for patients with uterine carcinosarcomas compared with high-risk endometrial carcinomas (grade 3 endometrioid and non-endometrioid); 5-year survival rates: 42%, 77% and 57%, respectively. Our results support the monoclonal origin of uterine carcinosarcomas. The epithelial component determines prognosis by causing the majority of metastases and vascular invasion. To improve prognosis, treatment should focus on the epithelial tumor component of uterine carcinosarcomas. Modern Pathology (2011Pathology ( ) 24, 1368Pathology ( -1379 doi:10.1038/modpathol.2011; published online 13 May 2011Keywords: carcinogenesis; clinical behavior; epithelial component; immunohistochemistry; uterine carcinosarcomas Uterine carcinosarcomas (malignant mixed Mü llerian tumors) are rare malignancies of the female genital tract, accounting for 1-5% of uterine malignancies. 1,2 Microscopically, carcinosarcomas consist of two histological malignant components: an epithelial (carcinoma) and a mesenchymal (sarcoma) component. The epithelial component is usually a

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Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

et al. 2011

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“…The main non-hematological toxicity was grade 2 gastrointestinal reactions in 2 patients and grade 1 in the remaining 2 patients. There were no severe adverse reactions to BEV, such as bowel perforation, bleeding or blood vessel embolism, high blood pressure, or severe proteinuria (14). Thus, it may be safe to use BEV combined with chemotherapy to treat advanced persistent and/or recurrent uterine sarcomas.…”

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confidence: 95%

Curative effect of bevacizumab combined with chemotherapy in advanced or recurrent uterine sarcoma

Han

Holt

et al. 2015

Molecular and Clinical Oncology

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Abstract. The aim of this study was to investigate the clinical effect of bevacizumab (BEV) combined with chemotherapy in advanced or recurrent uterine sarcoma. The clinical data of 4 patients with advanced or recurrenct uterine sarcoma, who received treatment with BEV combined with chemotherapy in our hospital between May, 2006 and May, 2014, were retrospectively analyzed. We estimated the chemotherapy response rate [complete response (CR) + partial response (PR)], clinical benefit rate [CR + PR+ stable disease (SD)], progression-free survival (PFS) and overall survival (OS), and evaluated treatment safety and toxicity reactions. Of the 4 patients, 1 achieved CR, with a disease-free survival time of 96 months; 1 achieved PR, with a PFS of 13 months and an OS of 25 months; 1 achieved SD, with a PFS of 9 months and an OS of 24 months; and 1 developed progressive disease, with a PFS of 3 months and an OS of 9 months. The response rate (CR+PR) was 50%, and the clinical benefit rate (CR+PR+SD) was 75%. Treatment-related adverse reactions occurred in all 4 patients, including bone marrow suppression and gastrointestinal reactions. Of the 4 patients, 1 developed grade 4 bone marrow suppression (thrombocytopenia), whereas the remaining 3 patients developed grade 2 bone marrow suppression (leukopenia). Of the 4 cases, 2 developed grade 2 gastrointestinal reactions, and the remaining 2 patients grade 1 gastrointestinal reactions. Therefore, BEV combined with chemotherapy was able to effectively control advanced or recurrent uterine sarcoma, was well-tolerated, and is considered to be a safe and effective candidate treatment for this type of tumor.

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“…Ifosfamide is the most active single agent for carcinosarcoma. Ifosfamide±cisplatin yielded favorable results in the adjuvant setting whereas ifosfamide-paclitaxel regimen clearly demonstrated a superior overall survival in the advanced setting (Homesley et al, 2007). However, this treatment is inconvenient, costly and toxicity is considerable.…”

Section: Discussionmentioning

confidence: 99%

“…GOG0108 previously showed that ifosfamide plus cisplatin offers a slight prolongation of progression-free survival but no significant overall survival benefit over ifosfamide alone in patients with advanced, persistent, or recurrent carcinosarcoma (Sutton et al, 2000). GOG0161 is the first randomized prospective trial in uterine carcinosarcoma that clearly demonstrates a superior overall survival for combination (ifosfamide and paclitaxel) chemotherapy compared to single agent treatment (ifosfamide) in the advanced setting (Homesley et al, 2007). On the other hand, data in the adjuvant treatment is more scarce.…”

Section: Introductionmentioning

confidence: 99%

Impact of Treatment Strategies on Local Control and Survival in Uterine Carcinosarcomas in Turkey

Küçüköztaş

Dizdar²,

Rahatli³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcomas treated in our institution. Materials and Methods: Records of 26 patients diagnosed between 2007 and 2011 with uterine carcinosarcoma were retrospectively evaluated for demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of DFS and OS Results: Median age was 61 (range 43-78). 10 patients (38%) had stage I disease at diagnosis, 3 (12%) had stage II, 4 (15%) had stage III and 9 (35%) had stage IV. Sixteen patients (62%) received chemotherapy with paclitaxel and carboplatin for 6 cycles. One patient underwent radiotherapy. Median follow up was 17 months. Sixteen patients relapsed and 13 died during follow up. Considering recurrence, 5 out of 16 patients had lung metastases, one had brain metastases and 9 had only intraabdominal recurrence. The 3 year DFS was 37% and the 3 year OS was 30%. Conclusions: Our data show that uterine carcinosarcomas tend to be at advanced stage at diagnosis and despite the use of chemotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates.

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Phase III Trial of Ifosfamide With or Without Paclitaxel in Advanced Uterine Carcinosarcoma: A Gynecologic Oncology Group Study

Abstract: OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.

Cited by 242 publications

References 15 publications

Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

Curative effect of bevacizumab combined with chemotherapy in advanced or recurrent uterine sarcoma

Impact of Treatment Strategies on Local Control and Survival in Uterine Carcinosarcomas in Turkey

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