Wendy Muñoz-Montaño1, Sae Muñiz-Hernández2, Alejandro Avilés-Salas3, Rodrigo Catalán1,4, Luis Lara-Mejía1, Suraj Samtani-Bassarmal5, Andres F Cardona6,7, Jorge Mendoza-Desión4, Daniel Hernández-Cueto8, Altagracia Maldonado8, Guillermina Baay-Guzmán8, Sara Huerta-Yepes8, Oscar Arrieta9,10. 1. Thoracic Oncology Unit, Instituto Nacional de Cancerología, San Fernando 22 Sección XVI, Tlalpan, 14080, Mexico City, Mexico. 2. Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, San Fernando 22 Sección XVI, Tlalpan, 14080, Mexico City, Mexico. sayide@hotmail.com. 3. Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico. 4. Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, San Fernando 22 Sección XVI, Tlalpan, 14080, Mexico City, Mexico. 5. Department of Oncology, Bradford Hill, Santiago, Chile. 6. Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia. 7. Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia. 8. Molecular Markers Laboratory, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, Mexico. 9. Thoracic Oncology Unit, Instituto Nacional de Cancerología, San Fernando 22 Sección XVI, Tlalpan, 14080, Mexico City, Mexico. ogarrieta@gmail.com. 10. Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, San Fernando 22 Sección XVI, Tlalpan, 14080, Mexico City, Mexico. ogarrieta@gmail.com.
Abstract
BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a rare but aggressive neoplasia that usually presents at advanced stages. Even though some advances have been achieved in the management of patients with MPM, this malignancy continuous to impose a deleterious prognosis for affected patients (12-18 months as median survival, and 5-10% 5-year survival rate), accordingly, the recognition of biomarkers that allow us to select the most appropriate therapy are necessary. METHODS: Immunohistochemistry semi-quantitative analysis was performed to evaluate four different biomarkers (ERCC1, RRM1, RRM2, and hENT-1) with the intent to explore if any of them was useful to predict response to treatment with continuous infusion gemcitabine plus cisplatin. Tissue biopsies from patients with locally advanced or metastatic MPM were analyzed to quantitatively asses the aforementioned biomarkers. Every included patient received treatment with low-dose gemcitabine (250 mg/m2) in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks as first-line therapy. RESULTS: From the 70 eligible patients, the mean and standard deviation (SD) for ERCC1, RRM1, RRM2 and hENT-1 were 286,178.3 (± 219, 019.8); 104,647.1 (± 65, 773.4); 4536.5 (± 5, 521.3); and 2458.7 (± 4, 983.4), respectively. Patients with high expression of RRM1 had an increased median PFS compared with those with lower expression (9.5 vs 4.8 months, p = < 0.001). Furthermore, high expression of RRM1 and ERCC1 were associated with an increased median OS compared with their lower expression counterparts; [(23.1 vs 7.2 months for RRM1 p = < 0.001) and (17.4 vs 9.8 months for ERCC1 p = 0.018)]. CONCLUSIONS: ERCC1 and RRM1 are useful biomarkers that predict better survival outcomes in patients with advanced MPM treated with continuous infusion of gemcitabine plus cisplatin.
BACKGROUND:Malignant Pleural Mesothelioma (MPM) is a rare but aggressive neoplasia that usually presents at advanced stages. Even though some advances have been achieved in the management of patients with MPM, this malignancy continuous to impose a deleterious prognosis for affected patients (12-18 months as median survival, and 5-10% 5-year survival rate), accordingly, the recognition of biomarkers that allow us to select the most appropriate therapy are necessary. METHODS: Immunohistochemistry semi-quantitative analysis was performed to evaluate four different biomarkers (ERCC1, RRM1, RRM2, and hENT-1) with the intent to explore if any of them was useful to predict response to treatment with continuous infusion gemcitabine plus cisplatin. Tissue biopsies from patients with locally advanced or metastatic MPM were analyzed to quantitatively asses the aforementioned biomarkers. Every included patient received treatment with low-dose gemcitabine (250 mg/m2) in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks as first-line therapy. RESULTS: From the 70 eligible patients, the mean and standard deviation (SD) for ERCC1, RRM1, RRM2 and hENT-1 were 286,178.3 (± 219, 019.8); 104,647.1 (± 65, 773.4); 4536.5 (± 5, 521.3); and 2458.7 (± 4, 983.4), respectively. Patients with high expression of RRM1 had an increased median PFS compared with those with lower expression (9.5 vs 4.8 months, p = < 0.001). Furthermore, high expression of RRM1 and ERCC1 were associated with an increased median OS compared with their lower expression counterparts; [(23.1 vs 7.2 months for RRM1 p = < 0.001) and (17.4 vs 9.8 months for ERCC1 p = 0.018)]. CONCLUSIONS:ERCC1 and RRM1 are useful biomarkers that predict better survival outcomes in patients with advanced MPM treated with continuous infusion of gemcitabine plus cisplatin.
Authors: Vanya Delgermaa; Ken Takahashi; Eun-Kee Park; Giang Vinh Le; Toshiyuki Hara; Tom Sorahan Journal: Bull World Health Organ Date: 2011-06-13 Impact factor: 9.408
Authors: Michel B Choueiri; John Paul Shen; Andrew M Gross; Justin K Huang; Trey Ideker; Paul Fanta Journal: PLoS One Date: 2015-06-17 Impact factor: 3.240