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Br J Cancer. 2018 May;118(11):1419-1424. doi: 10.1038/s41416-018-0068-z. Epub 2018 Apr 26.

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

Author information

1
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
2
Department of Medical Oncology, University of California at San Diego, San Diego, CA, 92103, USA.
3
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
4
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
5
Sarah Cannon Research Institute at HealthONE, Denver, CO, 80218, USA.
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
7
Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
8
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
9
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. dshong@mdanderson.org.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01113476.

PMID:
29695765
PMCID:
PMC5988803
DOI:
10.1038/s41416-018-0068-z
[Indexed for MEDLINE]
Free PMC Article

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