Developments in the systemic treatment of endometrial cancer.
Systemic treatment represents the cornerstone of endometrial cancer management in advanced, relapsed and metastatic disease, which is still characterized by poor prognosis. Progestins remain an effective option for patients with low grade, estrogen and/or progesterone receptor positive disease, with some of them achieving prolonged survival. Platinum compounds, anthracyclines and more recently taxanes have been implemented in combination regimens achieving response rates more than 50% and resulting in overall survival above 1 year in randomized trials. Adjuvant chemotherapy with the same agents may be useful for patients with early stage disease and high-risk features, such as high grade or non-endometrioid histology. Combination of chemotherapeutic agents with radiotherapy remains investigational. Hematologic, cardiac toxicity and neurotoxicity represent the main concern of chemotherapy and increase the risk for treatment-related morbidity and death, especially in pretreated patients bearing substantial co-morbidities. The gradual elucidation of the molecular aspects of endometrial carcinogenesis has led to the development of novel, selective antineoplastic agents, targeting specific molecular pathways and mediators of signal transduction implemented in cell proliferation, survival and angiogenesis. In the current review, we report on the recent advances regarding systemic therapy of endometrial carcinoma with special emphasis on results of large, randomized phase III clinical trials. Biomarkers with potent prognostic significance or predictive value for response to treatment are presented and novel molecular agents showing promising results in early clinical trials are discussed.
Mountzios
Giannis
G
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece. gmountzios@med.uoa.gr
Pectasides
Dimitrios
D
Bournakis
Evangelos
E
Pectasides
Eirini
E
Bozas
George
G
Dimopoulos
Meletios-A
MA
Papadimitriou
Christos A
CA
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D018943:Anthracyclines / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use / Q000633:toxicity; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D016889:Endometrial Neoplasms / Q000473:pathology / Q000628:therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000008:administration & dosage; D011372:Progestins / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D017671:Platinum Compounds; D011372:Progestins; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; D000068878:Trastuzumab