RESUMEN
BACKGROUND: Olaparib (AZD2281) is a potent oral poly(ADP-ribose) polymerase inhibitor with anti-tumour activity and acceptable toxicity as monotherapy in patients with BRCA-deficient cancers. The vascular endothelial growth factor receptor inhibitor bevacizumab has been incorporated into standard of care with chemotherapy in various tumours. This phase I study established the safety, tolerability and clinical pharmacokinetics of olaparib alone and in combination with bevacizumab. METHODS: Patients with advanced solid tumours received increasing doses of continuous oral olaparib (100, 200 and 400 mg b.i.d. capsule formulation) in combination with bevacizumab (10 mg kg(-1) intravenous q2w). RESULTS: In all, 12 patients enrolled and received treatment. The most common adverse events (AEs) related to olaparib were grade 1/2 nausea and fatigue. No haematological parameters were reported as AEs. No serious AEs related to olaparib or dose-limiting toxicities (DLTs) were reported. Three patients discontinued due to AEs, two patients discontinued both olaparib and bevacizumab and one patient discontinued olaparib. Five patients received combination treatment for over 6 months. There was no evidence that bevacizumab affected olaparib. CONCLUSION: The combination of olaparib 400 mg b.i.d. with bevacizumab 10 mg kg(-1) q2w was generally well tolerated with no DLTs. This combination could be considered for future clinical investigation.
Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ftalazinas/farmacocinética , Piperazinas/farmacocinética , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Administración Oral , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacocinética , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Ftalazinas/administración & dosificación , Ftalazinas/efectos adversos , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Breast cancer is the most common cancer in women and its incidence increases with age. Older women are not often offered optimal treatment compared with younger women for any particular stage. This is due to various reasons, including the lack of evidence for older women from well-conducted clinical trials. In this paper, the currently available evidences from clinical trials are reviewed and the various treatment options for older women with early breast cancer are discussed.