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

  • Author(s): 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
  • et al.
Abstract

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.

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