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Metronomic administration of chemotherapeutic agents as anti-angiogenic therapy

imatge Central Grup Recerca

Scientific Team

Researchers
Berta Laquente
Predoctoral researchers
Marta Vives

Introduction

Metronomic chemotherapy is a prolonged administration of cytotoxic drugs at low doses and without long breaks between cycles. This type of administration caused a mixed effect of cytotoxic anti-tumor and blocking tumor angiogenesis. And it has been shown positive results in both preclinical models and in clinical trials with patients with different tumors. Previous studies from the research group have shown that metronomic Gemcitabine blocks tumor growth in a preclinical murine model of pancreatic cancer and not only that, but the results suggest that the ability to block the dissemination of this tumor, responsible for its high mortality rate.

 

Our project proposes to study the effect of metronomic chemotherapy in orthotopic tumor dissemination in preclinical models of cancer and the combination of this form of administration with the conventional (so-called Chemo-switch) or other drugs may have synergistic effects. Our hypothesis is that the metronomic therapy may affect molecules involved in tumor dissemination and good coming from tumor cells although the cells composing the stroma. Pose for proteins and genes that may be differentially regulated by metronomic treatment and see if the modification of its expression affects the ability of migration and invasion of tumor cells.


Research group

Tumour Angiogenesis

Research lines

. Combinations of chemotherapy regimens (chem-switch) as a new therapeutic strategy.

 

. Effect of the metronome on tumor dissemination: molecular basis.

 

. Correlative biological studies to clinical trials


Group publications

 

B. Laquente, F. Viñals & J.R. Germà. "Metronomic chemotherapy: an antiangiogenic scheduling”. Clinical & Translational Oncology 9: 93-98, 2007.

 

B. Laquente, C Lacasa, M.M. Ginestà, O Casanovas, A. Figueras, M. Galán, I. García Ribas, J. R. Germà, G. Capellà & F. Viñals. “Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model”. Molecular Cancer Therapeutics 7: 638-647, 2008.

 

Collaborations


Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. “Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma”. Int J Radiat Oncol Biol Phys. 75:1430-6, 2009.

 

Fabregat J, Busquets J, Peláez N, Jorba R, García-Borobia F, Masuet C, Valls C, Ruiz-Osuna S, Serrano T, Galán M, Cambray M, Laquente B, Ramos E, Rafecas A.:”Surgical treatment of pancreatic adenocarcinoma using cephalic duodenopancreatectomy (Part 2). Long term follow up after 204 cases”. Cir Esp. 88: 374-82 2010.

 

Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumour Therapy (TTD). “Phase II trial of induction irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for unresectable, locally advanced gastric and oesophageal-gastric junction adenocarcinoma”. Cancer Chemother Pharmacol. 67:75-82, 2011.


Estudi de marcadors predictius de resposta al tractament pre-quirúrgic en el càncer de recte localment avançat. Conveni amb ROCHE Pharma.
Coordinació nacional:  “Estudio del perfil angiogénico asociado al estudio TTD-08-05 titulado “Estudio fase II randomizado de Capecitabina + Bevacizumab + radioterapia externa versus Capecitabina + radioterapia externacomo tratamiento preoperatorio en pacientes con cáncer rectal localmente avanzado resecable” Título abreviado: AVAXEL. Código de protocolo: TTD-08-05 NºEudraCT: 2009-010192-24.IP Ramón Salazar
Estudi biològic correlatiu a l'assaig clínic: ”Estudio de fase II de tratamiento neoadyuvante con gemcitabina, Tarceva® y oxaliplatino, seguido de quimiorradioterapia con Tarceva® y gemcitabina en pacientes con adenocarcinoma pancreático de resecabilidad borderline.” Título abreviado: GEMERLOXA Código del promotor: ICO-20431 EudraCT: 2010-021872-27  
Investigació clínica: assaigs oberts
”Estudio de fase II de tratamiento neoadyuvante con gemcitabina, Tarceva® y oxaliplatino, seguido de quimiorradioterapia con Tarceva® y gemcitabina en pacientes con adenocarcinoma pancreático de resecabilidad borderline.” Título abreviado: GEMERLOXA Código del promotor: ICO-20431 EudraCT: 2010-021872-27 IP: Berta Laquente
PM 1183-B-001-10 A Phase II study of PM 01183 as Second Line treatment in patients with Metastatic Pancreatic Cancer. PM01183 Código del protocolo: PM1183-B-001-10Número EudraCT: 2010-024292-. IP Berta Laquente
Safety Run and Phase II randomized trial of MEK inhibitor MSC1936369B or placebo combined with gemcitabine in metastatic pancreas cancer subjects. EudraCT Number 2009-011992-61 Coordinating Investigator Prof. Eric Van Cutsem. IP Berta Laquente.
Estudio fase II con axitinib como tratamiento de mantenimiento en pacientes con Carcinoma Colorrectal metastático. Nº de protocolo: TTD-11-01/AXI-IIG-01Nº EudraCT: 2011-002384-16. Coordinadores nacionales: Cristina Grávalos y Alfredo Carrato. IP: Berta Laquente
Protocolo I2I-MC-JMMC(b) Estudio fase 1 / fase 2 (aleatorizado) para evaluar LY2603618 en combinación con gemcitabina en pacientes con cáncer de páncreas. IP: Silvia Vázquez. Co-investigadora: Berta Laquente.
Estudio fase II abierto, no aleatorizado, para evaluar la eficacia y seguridad del tratamiento neoadyuvante concomitante de Gemcitabina y Erlotinib seguido de Gemcitabina, Erlotinib y radioterapia en pacientes con adenocarcinoma resecable de páncreas. GEMCAD 1003 Nº EudraCT:2010-021738-72.Coordinador: Joan Maurel. IP Silvia Vázquez. Co-investigadora Berta Laquente.
An open-label, multicenter, randomized, phase 3 study of S-1 and CISPLATIN compared with 5-FU and CISPLATIN in patients with metastatic diffuse gastric cancer previously untreated with chemotherapy S-1Protocol No.: TPU-S1303 IND No: 53,765EudraCT No: 2009-016019-39. IP: Mariona Calvo. Co-investigadora: Berta Laquente.

. Study of predictive markers of response to preoperative treatment in locally advanced rectal cancer. Agreement with Roche Pharma.

 

. National coordination:  “Estudio del perfil angiogénico asociado al estudio TTD-08-05 titulado “Estudio fase II randomizado de Capecitabina + Bevacizumab + radioterapia externa versus Capecitabina + radioterapia externacomo tratamiento preoperatorio en pacientes con cáncer rectal localmente avanzado resecable” Título abreviado: AVAXEL. Código de protocolo: TTD-08-05 NºEudraCT: 2009-010192-24.IP Ramón Salazar

 

. Biological Study correlative to clinical trial: ”Estudio de fase II de tratamiento neoadyuvante con gemcitabina, Tarceva® y oxaliplatino, seguido de quimiorradioterapia con Tarceva® y gemcitabina en pacientes con adenocarcinoma pancreático de resecabilidad borderline.” Título abreviado: GEMERLOXA Código del promotor: ICO-20431 EudraCT: 2010-021872-27  

 

Clinical research: open trials

 

. ”Estudio de fase II de tratamiento neoadyuvante con gemcitabina, Tarceva® y oxaliplatino, seguido de quimiorradioterapia con Tarceva® y gemcitabina en pacientes con adenocarcinoma pancreático de resecabilidad borderline.” Título abreviado: GEMERLOXA Código del promotor: ICO-20431 EudraCT: 2010-021872-27 IP: Berta Laquente

 

. PM 1183-B-001-10 A Phase II study of PM 01183 as Second Line treatment in patients with Metastatic Pancreatic Cancer. PM01183 Código del protocolo: PM1183-B-001-10Número EudraCT: 2010-024292-. IP Berta Laquente

 

. Safety Run and Phase II randomized trial of MEK inhibitor MSC1936369B or placebo combined with gemcitabine in metastatic pancreas cancer subjects. EudraCT Number 2009-011992-61 Coordinating Investigator Prof. Eric Van Cutsem. IP Berta Laquente.

 

. Estudio fase II con axitinib como tratamiento de mantenimiento en pacientes con Carcinoma Colorrectal metastático. Nº de protocolo: TTD-11-01/AXI-IIG-01Nº EudraCT: 2011-002384-16. Coordinadores nacionales: Cristina Grávalos y Alfredo Carrato. IP: Berta Laquente

 

. Protocolo I2I-MC-JMMC(b) Estudio fase 1 / fase 2 (aleatorizado) para evaluar LY2603618 en combinación con gemcitabina en pacientes con cáncer de páncreas. IP: Silvia Vázquez. Co-investigadora: Berta Laquente.

 

. Estudio fase II abierto, no aleatorizado, para evaluar la eficacia y seguridad del tratamiento neoadyuvante concomitante de Gemcitabina y Erlotinib seguido de Gemcitabina, Erlotinib y radioterapia en pacientes con adenocarcinoma resecable de páncreas. GEMCAD 1003 Nº EudraCT:2010-021738-72.Coordinador: Joan Maurel. IP Silvia Vázquez. Co-investigadora Berta Laquente.

 

. An open-label, multicenter, randomized, phase 3 study of S-1 and CISPLATIN compared with 5-FU and CISPLATIN in patients with metastatic diffuse gastric cancer previously untreated with chemotherapy S-1Protocol No.: TPU-S1303 IND No: 53,765EudraCT No: 2009-016019-39. IP: Mariona Calvo. Co-investigadora: Berta Laquente.

imatge personal
 

Subgroup head (PI)

Berta Laquente
E-mail  
blaquente@idibell.cat
 
© 2017 Institut d'Investigació Biomèdica de Bellvitge



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