Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study

Fleming, Gini F.; Filiaci, Virginia L.; Bentley, Rex C.; Herzog, Thomas J.; Sorosky, Joel I.; Vaccarello, Luis; Gallion, Holly H.

doi:10.1093/annonc/mdh316

Cited by 201 publications

(93 citation statements)

References 25 publications

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“…For patients with advanced disease (stage III and IV) a combination of chemotherapy with cisplatin and doxorubicin has been found to be superior to radiotherapy (8). Newer agents such as paclitaxel have shown promising survival and response rates in endometrial cancer patients as a single agent or in combination with cisplatin/carboplatin and doxorubicin chemotherapy (9). It remains to be seen whether adjuvant chemotherapy in patients with high-risk disease in a lower stage will improve survival and possibly replace adjuvant radiotherapy in some groups of patients (10).…”

Section: Introductionmentioning

confidence: 99%

High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion

Muinelo‐Romay

Colás

Barbazán

et al. 2011

Molecular Cancer Therapeutics

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Endometrial cancer is among the three most common cancers in females in industrialized countries. In the majority of cases, the tumor is confined to the uterus at the time of diagnosis and presents a good prognosis. However, after primary surgery, 15% to 20% of these tumors recur and have limited response to systemic therapy. We carried out gene expression profiling of high-risk recurrence endometrial cancers to identify new therapeutic approaches targeting the molecular pathways involved in the acquisition of an aggressive tumor phenotype. A microarray gene-expression analysis on a total of 51 human endometrial carcinomas revealed 77 genes specifically altered in high-risk recurrence tumors (P < 0.001). The bioinformatics analysis of gene-gene interactions and molecular relationships among these genes pointed to a prominent role for TGFb1 signaling in the acquisition of an aggressive phenotype. We further showed that TGF-b1 has a principal role at the initiation of endometrial carcinoma invasion through the promotion of the epithelial to mesenchymal transition that leads to the acquisition of an invasive phenotype in HEC-1A and RL95-2 cells. Impairment of this initial step with SB-431542, a specific TGF-b1 inhibitor, precluded further persistent endometrial carcinoma invasion. In conclusion, we showed that the characterization of the molecular changes associated with the acquisition of an aggressive phenotype represents a realistic strategy for the rational identification and characterization of new potential therapeutic targets in an effort to improve the clinical management and the outcome of high-risk endometrial cancer patients. Mol Cancer Ther; 10(8); 1357-66. '2011 AACR.

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Section: Introductionmentioning

confidence: 99%

High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion

Muinelo‐Romay

Colás

Barbazán

et al. 2011

Molecular Cancer Therapeutics

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“…Cytotoxic agents including doxorubicin, cisplatin, carboplatin, and paclitaxel have demonstrated activity in phase II studies, and have been studied alone or in combination in several phase III trials. In patients with measurable, advanced or recurrent disease, response rates of 27-54% have been reported [2][3][4]. For patients with advanced stage disease, chemotherapy has been increasingly integrated into first-line therapy.…”

Section: Introductionmentioning

confidence: 99%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

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Objectives-A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome.Methods-Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens.Results-Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival Précis: Thalidomide has minimal activity in chemo-refractory endometrial cancer as judged by the ability to prolong progression-free survival greater than 6 months.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…3 This finding contributed to the development of Gynecologic Oncology Group protocol 163, which compared doxorubicin and paclitaxel versus doxorubicin plus cisplatin. 4 This trial failed to demonstrate a significant difference in RR, PFS, or OS between the 2 arms, and doxorubicin plus cisplatin remained the standard of care. Gynecologic Oncology Group protocol 177 compared doxorubicin plus cisplatin versus doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2; the latter was superior to doxorubicin plus cisplatin in terms of overall RR (57% vs 34%; P < .01) and median PFS (8.3 vs 5.3 months; P < .01), and for the first time OS was superior, with a median of 15.3 (doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2) versus 12.3 months (doxorubicin plus cisplatin) (P ¼ .037).…”

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confidence: 97%

Does the progression‐free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?

Moore

Tian

McMeekin

et al. 2010

Cancer

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BACKGROUND: This study evaluated whether progression-free interval (PFI) following primary chemotherapy (PCT) was predictive of overall survival (OS) after second-line chemotherapy in advanced/recurrent endometrial cancer (EC). METHODS: This is a pooled analysis of patients who recurred after PCT and were treated with second-line chemotherapy on Gynecologic Oncology Group trials. PFI-1 measured from initiation of PCT to recurrence or treatment-free interval (TFI) measured from completion of PCT to initiation of second-line chemotherapy was evaluated in relation to clinical outcomes. RESULTS: A total of 586 patients treated on 5 phase 3 PCT protocols were included. Baseline factors in primary setting associated with clinical outcome after PCT were also predictive of OS after second-line chemotherapy, including race, Gynecologic Oncology Group performance status, grade, and prior radiation therapy (P < .01). PFI-1 was the most significant factor predictive of survival after second-line chemotherapy, with a 30% reduction in the risk of death for PFI-1 >6 months compared with 6 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.59-0.84 [P < .0001]) and median OS after second-line chemotherapy of 10 versus 5 months. A total of 275 patients treated on 9 phase 2 second-line chemotherapy protocols were also evaluated, and TFI >3 months was associated with a 25% reduction in the risk of death (HR, 0.75; 95% CI,) and median OS after second-line chemotherapy of 10 versus 7 months compared with TFI 3 months. The tumor response to second-line chemotherapy was 9.6% versus 5.8%; the difference was not statistically significant. CONCLUSIONS: Time to recurrence after PCT is predictive of survival after recurrence in advanced/recurrent EC. However, there is no evidence that this variable can be used in selecting salvage chemotherapy.

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Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study

Abstract: Doxorubicin and 24-h paclitaxel plus filgrastim was not superior to doxorubicin and cisplatin in terms of response, PFS or survival in advanced endometrial cancer.

Cited by 201 publications

References 25 publications

High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion

High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

Does the progression‐free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?

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