TY - JOUR
T1 - Phase i study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers
AU - Sen, Shiraj
AU - Kato, Shumei
AU - Agarwal, Rishi
AU - Piha-Paul, Sarina
AU - Hess, Kenneth
AU - Karp, Daniel
AU - Janku, Filip
AU - Fu, Siqing
AU - Naing, Aung
AU - Pant, Shubham
AU - Falchook, Gerald
AU - Tang, Chad
AU - Wu, Xifeng
AU - Ye, Yuanqing
AU - Tsimberidou, Apostolia
AU - Subbiah, Vivek
AU - Kurzrock, Razelle
AU - Byers, Lauren
AU - Westin, Shannon
AU - Lim, Jo Ann
AU - Bean, Stacie
AU - Bass, Allison
AU - Nguyen, Ly
AU - Meric-Bernstam, Funda
AU - Hong, David
N1 - Publisher Copyright:
© 2018 Cancer Research UK.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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/m2 nab-paclitaxel and 15 mg/kg bevacizumab with 1000 mg/m2 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/m2, nab-paclitaxel 125 mg/m2, and bevacizumab 15 mg/kg. VEGF polymorphism data should be evaluated in future bevacizumab-based trials.
AB - 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/m2 nab-paclitaxel and 15 mg/kg bevacizumab with 1000 mg/m2 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/m2, nab-paclitaxel 125 mg/m2, and bevacizumab 15 mg/kg. VEGF polymorphism data should be evaluated in future bevacizumab-based trials.
UR - http://www.scopus.com/inward/record.url?scp=85046021462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046021462&partnerID=8YFLogxK
U2 - 10.1038/s41416-018-0068-z
DO - 10.1038/s41416-018-0068-z
M3 - Article
C2 - 29695765
AN - SCOPUS:85046021462
SN - 0007-0920
VL - 118
SP - 1419
EP - 1424
JO - British journal of cancer
JF - British journal of cancer
IS - 11
ER -