Phase II Study of Erlotinib in Recurrent or Metastatic Endometrial Cancer: NCIC IND-148

Oza, Amit M.; Eisenhauer, Elizabeth; Elit, Laurie; Cutz, Jean Claude; Sakurada, Akira; Tsao, Ming‐Sound; Hoskins, Paul; Biagi, Jim; Ghatage, Prafull; John, Mary; Provencher, Diane; Dore, Naomi; Dancey, Janet; Fyles, Anthony

doi:10.1200/jco.2007.15.8808

Cited by 131 publications

(61 citation statements)

References 23 publications

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“…Interestingly, because TGF-b1 signals seem to play a critical function for EGF-promoted invasion, the combination of both TGF-b1 and EGFR inhibitors could be promising as a therapeutic strategy. To this regard, Erlotinib has shown an overall objective response rate of 12.5% in recurrent or metastatic endometrial cancer (38). In addition, the integration of oncology parameters associated with an aggressive phenotype (i.e., the TGF-b1 pathway) together with the histopathology parameters actually used in the clinic would help to better stratify increased risk of recurrence.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Three of them had partial responses (PR) (16%), seven (37%) had SD, and eight had progressive diseases, and one was not assessable. Erlotinib was well tolerated with 12.5% overall objective response rate (Oza et al, 2008).…”

Section: 3419 Molecular Therapy As a Future Strategy For Endometrialmentioning

confidence: 99%

“…A phase II study was performed to evaluate single-agent activity of erlotinib in patients with advanced, recurrent disease who were chemotherapy naïve and had received up to one line of prior hormonal therapy (Oza et al, 2008). It was administered at daily dose of 150 mg, and thirty-two patients were evaluated.…”

Section: 3419 Molecular Therapy As a Future Strategy For Endometrialmentioning

confidence: 99%

Molecular Therapy as a Future Strategy in Endometrial Cancer

Thanapprapasr¹,

Thanapprapasr²

2013

Asian Pacific Journal of Cancer Prevention

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Of all gynecologic cancers, endometrial cancer is the most common cancer in the US and Europe. In addition, it is presently the second most common gynecologic cancer in the world. As a result of increasing menopausal, obese and tamoxifen use women, the incidence of the cancer seems to be on the increase. Surgery is the major treatment, whereas postoperative radiation therapy in high-intermediate risk patients many prevent locoregional recurrence. Adjuvant chemotherapy can improve progression free survival in advanced or recurrent cancers. Molecular targeted therapies are now a focus of attention including anti-vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) inhibitor and tyrosine kinase inhibitor (TKI). They may provide useful future strategies for control of endometrial malignancies in developing countries and across the world.

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“…The results of the existing Phase II trial were not promising [26] with 4 partial responses out of 34 enrolled patients. There are currently no ongoing trials.…”

Section: Erlotinibmentioning

confidence: 99%

Emerging molecular-targeted therapies—the challenging case of endometrial cancer

Vasconcelos¹

2015

Adv Mod Oncol Res

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Endometrial cancer newly affects an estimated 54,870 women in the United States, being responsible for an estimated 10,170 deaths in 2015. It has demonstrated to harbor a complex carcinogenesis process, with limited treatment options for advanced or persistent disease. Identification and targeting of genetic alterations that lead to progressive disease and therapy resistance is not only challenging, but also often does not correlate with a clinical benefit. Targeted maintenance therapies in endometrial cancer have been largely disappointing. Nonetheless, targeted personalized treatment should be the main goal of treatment of advanced disease in the future. Due to the high variety of drugs being tested in early clinical trials, it is hard to keep pace with the latest developments and ongoing trials. This review aims to summarize the latest published and ongoing trials on targeted therapies in endometrial cancer.

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Phase II Study of Erlotinib in Recurrent or Metastatic Endometrial Cancer: NCIC IND-148

Abstract: Erlotinib is well tolerated with an overall objective response rate of 12.5%. Molecular analysis did not identify EGFR mutations in responders or correlation of response with gene amplification.

Cited by 131 publications

References 23 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

Molecular Therapy as a Future Strategy in Endometrial Cancer

Emerging molecular-targeted therapies—the challenging case of endometrial cancer

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