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Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers

BACKGROUND: We performed a phase I modified 3 + 3 dose escalation study to evaluate the safety and activity of bevacizumab plus gemcitabine and nab-paclitaxel in patients with advanced solid tumours. METHODS: Patients were given fixed dose gemcitabine plus increasing doses of nab-paclitaxel and beva...

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Detalles Bibliográficos
Autores principales: Sen, Shiraj, Kato, Shumei, Agarwal, Rishi, Piha-Paul, Sarina, Hess, Kenneth, Karp, Daniel, Janku, Filip, Fu, Siqing, Naing, Aung, Pant, Shubham, Falchook, Gerald, Tang, Chad, Wu, Xifeng, Ye, Yuanqing, Tsimberidou, Apostolia, Subbiah, Vivek, Kurzrock, Razelle, Byers, Lauren, Westin, Shannon, Lim, JoAnn, Bean, Stacie, Bass, Allison, Nguyen, Ly, Meric-Bernstam, Funda, Hong, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988803/
https://www.ncbi.nlm.nih.gov/pubmed/29695765
http://dx.doi.org/10.1038/s41416-018-0068-z
Descripción
Sumario:BACKGROUND: We performed a phase I modified 3 + 3 dose escalation study to evaluate the safety and activity of bevacizumab plus gemcitabine and nab-paclitaxel in patients with advanced solid tumours. METHODS: Patients were given fixed dose gemcitabine plus increasing doses of nab-paclitaxel and bevacizumab. Toxicity, response, and association with VEGF polymorphism was analysed. RESULTS: The study enrolled 110 patients who had undergone a median of 3 prior lines of therapy. The median age was 60 years (range, 17–85 years), and 55 patients (50%) had gemcitabine-refractory disease. We observed 3 dose-limiting toxicities during dose escalation and 3 DLTs in expansion cohorts. Dose escalation to 150 mg/m(2) nab-paclitaxel and 15 mg/kg bevacizumab with 1000 mg/m(2) of gemcitabine was well tolerated with no MTD. One patient with gemcitabine-refractory peritoneal papillary carcinoma had a complete response, 13 patients (13%) had partial responses, and 54 patients (52%) had stable disease ≥12 weeks. Exploratory VEGF single nucleotide polymorphism (SNP) analysis was performed on 13 patients. CONCLUSIONS: The combination of gemcitabine, nab-paclitaxel, and bevacizumab is safe, well-tolerated, and has activity in advanced malignancies, including gemcitabine-refractory tumours. Based on this study, the recommended phase 2 dose is gemcitabine 1000 mg/m(2), nab-paclitaxel 125 mg/m(2), and bevacizumab 15 mg/kg. VEGF polymorphism data should be evaluated in future bevacizumab-based trials.