title: Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study).
abstract: BACKGROUND
  Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer.
  
  
  METHODS
  Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method).
  
  
  RESULTS
  The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%.
  
  
  CONCLUSIONS
  The combination allows the delivery of full-dose intensity, while efficacy seems promising.
authors: 1] CNIO-Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain [2] MD Anderson Cancer Center, Arturo Soria, 270, 28033 Madrid, Spain [3] Hospital de Fuenlabrada, Camino del Molino, 2, 28942 Fuenlabrada, Madrid, Spain.
authors: M
authors: M
authors: Quintela-Fandino
authors: Instituto Catalan de Oncologia-Hospital Duran i Reynals-IDIBELL, Gran Via de l'Hospitalet, 199, 08907 L'Hospitalet de Llobregat, Spain.
authors: A
authors: A
authors: Urruticoechea
authors: Hospital de Fuenlabrada, Camino del Molino, 2, 28942 Fuenlabrada, Madrid, Spain.
authors: J
authors: J
authors: Guerra
authors: Instituto Catalan de Oncologia-Hospital Duran i Reynals-IDIBELL, Gran Via de l'Hospitalet, 199, 08907 L'Hospitalet de Llobregat, Spain.
authors: M
authors: M
authors: Gil
authors: MD Anderson Cancer Center, Arturo Soria, 270, 28033 Madrid, Spain.
authors: A
authors: A
authors: Gonzalez-Martin
authors: MD Anderson Cancer Center, Arturo Soria, 270, 28033 Madrid, Spain.
authors: R
authors: R
authors: Marquez
authors: 1] CNIO-Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain [2] Hospital de Fuenlabrada, Camino del Molino, 2, 28942 Fuenlabrada, Madrid, Spain.
authors: E
authors: E
authors: Hernandez-Agudo
authors: GEICAM-Grupo Español de Investigación en Cancer de Mama, Avenida de los Pirineos, 7, 28700 San Sebastian de los Reyes, Spain.
authors: C
authors: C
authors: Rodriguez-Martin
authors: Instituto Catalan de Oncologia-Hospital Duran i Reynals-IDIBELL, Gran Via de l'Hospitalet, 199, 08907 L'Hospitalet de Llobregat, Spain.
authors: M
authors: M
authors: Gil-Martin
authors: MD Anderson Cancer Center, Arturo Soria, 270, 28033 Madrid, Spain.
authors: R
authors: R
authors: Bratos
authors: GEICAM-Grupo Español de Investigación en Cancer de Mama, Avenida de los Pirineos, 7, 28700 San Sebastian de los Reyes, Spain.
authors: M J
authors: MJ
authors: Escudero
authors: Boehringer Ingelheim RCV GmbH & Co KG, Dr Boehringer Gasse 5-11, Vienna 1121, Austria.
authors: S
authors: S
authors: Vlassak
authors: Boehringer Ingelheim Pharma GmbH & Co KG, Binger Strasse 173, 55216 Ingelheim, Germany.
authors: F
authors: F
authors: Hilberg
authors: CNIO-Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain.
authors: R
authors: R
authors: Colomer
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008231:Lymphopenia / Q000139:chemically induced; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D003520:Cyclophosphamide; D004317:Doxorubicin; D007211:Indoles; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D005723:gamma-Glutamyltransferase; C508053:ERBB2 protein, human; C530716:nintedanib