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A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification.
Tarpgaard, Line S; Qvortrup, Camilla; Nygård, Sune B; Nielsen, Signe L; Andersen, Diana R; Jensen, Niels Frank; Stenvang, Jan; Detlefsen, Sönke; Brünner, Nils; Pfeiffer, Per.
Afiliación
  • Tarpgaard LS; Department of Oncology, Odense University Hospital, Odense, Denmark. line.tarpgaard@rsyd.dk.
  • Qvortrup C; Department of Oncology, Odense University Hospital, Odense, Denmark. camilla.qvortrup@rsyd.dk.
  • Nygård SB; Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark. Sune.Boris.Nygaard@regionh.dk.
  • Nielsen SL; Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Sune.Boris.Nygaard@regionh.dk.
  • Andersen DR; Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark. siln@sund.ku.dk.
  • Jensen NF; Department of Oncology, Odense University Hospital, Odense, Denmark. diana.riise.andersen@rsyd.dk.
  • Stenvang J; Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark. tfm434@alumni.ku.dk.
  • Detlefsen S; Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark. stenvang@sund.ku.dk.
  • Brünner N; Department of Pathology, Odense University Hospital, Odense, Denmark. sonke.detlefsen@rsyd.dk.
  • Pfeiffer P; Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark. nbr@sund.ku.dk.
BMC Cancer ; 16: 91, 2016 Feb 11.
Article en En | MEDLINE | ID: mdl-26867764
UNLABELLED: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6% of these tumors had TOP2A copy gain and 2.0% had loss of TOP2A when compared to adjacent normal tissue. The TOP2A gene is located on chromosome 17 and when the TOP2A/CEN-17 ratio was applied to identify tumors with gene loss or amplifications, 10.5% had a ratio ≥ 1.5 consistent with gene amplification and 2.6% had a ratio ≤ 0.8 suggesting gene deletions. Based on these observations and the knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. METHODS/DESIGN: The study is an open label, single arm, phase II study, investigating the efficacy of epirubicin in patients with oxaliplatin refractory mCRC and with a cancer cell TOP2A/CEN-17 ratio ≥ 1.5. TOP2A gene amplification measured by fluorescence in situ hybridization. A total of 25 evaluable patients (15 + 10 in two steps) will be included (Simon's two-stage minimax design). Every nine weeks, response is measured by computed tomography imaging and evaluated according to RECIST 1.1. The primary end-point of the study is progression-free survival. TRIAL REGISTRATION: Eudract no. 2013-001648-79.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Pronóstico / Neoplasias Colorrectales / Epirrubicina / ADN-Topoisomerasas de Tipo II / Proteínas de Unión al ADN / Antígenos de Neoplasias Tipo de estudio: Clinical_trials / Guideline / Prognostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Dinamarca

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Pronóstico / Neoplasias Colorrectales / Epirrubicina / ADN-Topoisomerasas de Tipo II / Proteínas de Unión al ADN / Antígenos de Neoplasias Tipo de estudio: Clinical_trials / Guideline / Prognostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Dinamarca