Bleomycin, Etoposide, and Cisplatin Combination Therapy of Ovarian Granulosa Cell Tumors and Other Stromal Malignancies: A Gynecologic Oncology Group Study

Homesley, Howard D.; Bundy, Brian N.; Hurteau, Jean; Roth, Lawrence M.

doi:10.1006/gyno.1998.5304

Cited by 227 publications

(156 citation statements)

References 19 publications

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“…Recurrencies are rather common (reaching 30% in this study) and often present in locations where surgical removal is not feasible (5,47). Despite the developments in conventional chemotherapeutic combination treatments, mortality in recurrent GCT is high (5,6), and thus the most challenges rise in the treatment of recurrent GCTs.…”

Section: Discussionmentioning

confidence: 77%

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

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Objective: Ovarian granulosa cell tumors (GCTs) are hormonally active sex cord stromal tumors accounting for 3-5% of all ovarian cancers. These tumors are generally diagnosed at an early stage but there is a high risk of recurrence, associated with high mortality. Treatment of recurrent GCTs is difficult, and biologically targeted treatment modalities are lacking. GCTs are highly vascularized, and angiogenic factors most probably play a role in their pathology. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but in GCTs, the role of VEGF and its receptors VEGFR-1 (FLT1) and VEGFR-2 (KDR) remains largely unknown. Our objective is to study the expression of VEGF and its receptors in human GCTs. Methods: We analyzed GCTs from 106 patients for the expressions of VEGF and its receptors utilizing tumor tissue microarray, tumor mRNA, and patient serum samples. Results: We found that VEGF and its main biologically active receptor VEGFR-2 were highly expressed in primary and recurrent GCTs, when compared with normal granulosa-lutein cells. The expression of VEGF correlated positively to tumor microvessel density and to VEGFR-2 expression at the protein (P!0.05) and mRNA (P!0.05) levels. In contrast to VEGFR-2, the expression of VEGFR-1 was weak. Tumor VEGF protein expression was not prognostic for recurrence, however, we found high levels of circulating VEGF in the serum of patients with primary GCT. Conclusions:The results suggest an important role of VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF-or VEGFR-2-targeted treatments to patients with GCT.

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Section: Discussionmentioning

confidence: 77%

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

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“…8 The overall response rate to the BEP (bleomycin, etoposide, cisplatin) combination which is considered to be an effective regimen with tolerable toxicity as a first-line chemotherapy was reported as 83% in metastatic sex-cord stromal tumors of the ovary. 3,13 In this series, 53.8% of patients received adjuvant therapy due to advanced stage disease or high risk stage I disease. The adjuvant treatment modalities mainly included chemotherapy with or without radiotherapy.…”

Section: Discussionmentioning

confidence: 90%

Prognostic factors in adult granulosa cell tumors of the ovary: a retrospective analysis of 80 cases

et al. 2009

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Objective: Ovarian granulosa cell tumors are rare malignancies with a relatively favorable prognosis. However, patients still suffer from disease-related mortality. Therefore, the prognostic factors should be clarified. The purpose of this study was to investigate the clinical and pathologic characteristics related with disease recurrence and mortality in adult type ovarian granulosa cell tumors. Methods: Eighty surgically staged patients with granulosa cell ovarian tumor treated at the Hacettepe University Hospital between 1982 and 2006 were retrospectively reviewed. Clinical and pathological characteristics were analyzed. Results: Granulosa cell ovarian tumors accounted for 4.3% of malignant ovarian neoplasms. Mean age was 47.6 years. The most common presenting symptom was abnormal uterine bleeding (53.7%). Endometrial pathology was detected in 51.2% of patients preoperatively. Seventy percent of patients were diagnosed at stage I, and 53.8% of patients received adjuvant treatment. Mean follow-up was 67.5 months. Overall 5-year and 10-year survival was 91% and 86%, respectively. Mean survival was 147.1 months. Recurrence rate was 11.2%. In univariate analysis, advanced stage, advanced age, residual disease after surgery, and need for adjuvant treatment were associated with disease-related mortality and advanced stage disease and absence of initial staging surgery were associated with disease recurrence. However, in multivariate analysis, only initial stage was found to be a significant prognostic factor. Conclusion: Initial stage seems to be the single most important prognostic factor in ovarian granulosa cell tumors. Therefore, a comprehensive staging surgery should be attempted to document the real extent of disease and to estimate the oncologic outcome more accurately.

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“…Prognosis is good for most SCT of the ovary, although malignancy has been reported in as high as 28.6-43 % of cases [3,25]. Hayes and Scully [15] identified the pathological features most associated with malignancy: more than two mitoses per 10 high-power field, presence of necrosis, ≥7 cm, hemorrhage and nuclear atypia ≥ grade 2.…”

Section: Discussionmentioning

confidence: 99%

“…Chemotherapy should be based on malignant factors in histology examination and stage of the tumor. Few studies are available, but BEP (bleomycin, etoposide and cisplatin) appears to be an active first-line chemotherapy regimen for malignant stromal tumors [19,25].…”

Section: Discussionmentioning

confidence: 99%

Ovarian Steroid Cell Tumor Associated to Endometrial Hyperplasia and Presenting as Postmenopausal Vaginal Bleeding

Rubido¹,

Carrasco²

2015

Gynecol Obstet (Sunnyvale)

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Bleomycin, Etoposide, and Cisplatin Combination Therapy of Ovarian Granulosa Cell Tumors and Other Stromal Malignancies: A Gynecologic Oncology Group Study

Cited by 227 publications

References 19 publications

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Prognostic factors in adult granulosa cell tumors of the ovary: a retrospective analysis of 80 cases

Ovarian Steroid Cell Tumor Associated to Endometrial Hyperplasia and Presenting as Postmenopausal Vaginal Bleeding

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