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

Autor: Vivek Subbiah, Kenneth R. Hess, Funda Meric-Bernstam, Aung Naing, Rishi Agarwal, Shumei Kato, Daniel D. Karp, Jo Ann Lim, Filip Janku, Ly M. Nguyen, Apostolia Maria Tsimberidou, Shannon N. Westin, Xifeng Wu, Siqing Fu, Sarina Anne Piha-Paul, Shiraj Sen, Chad Tang, Allison Bass, Gerald Steven Falchook, Razelle Kurzrock, Lauren Averett Byers, David S. Hong, Shubham Pant, Yuanqing Ye, Stacie Bean
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Vascular Endothelial Growth Factor A
Male
Cancer Research
medicine.medical_treatment
Deoxycytidine
0302 clinical medicine
Neoplasms
Antineoplastic Combined Chemotherapy Protocols
80 and over
Young adult
Aged
80 and over
Middle Aged
3. Good health
Bevacizumab
Treatment Outcome
030220 oncology & carcinogenesis
Toxicity
Public Health and Health Services
Female
medicine.drug
Adult
medicine.medical_specialty
Paclitaxel
Maximum Tolerated Dose
Adolescent
Oncology and Carcinogenesis
Single-nucleotide polymorphism
and over
Article
Drug Administration Schedule
03 medical and health sciences
Young Adult
Genetic
Internal medicine
Albumins
medicine
Humans
In patient
Oncology & Carcinogenesis
Polymorphism
Aged
Chemotherapy
Polymorphism
Genetic
business.industry
Gemcitabine
Clinical trial
030104 developmental biology
business
Zdroj: British journal of cancer, vol 118, iss 11
British Journal of Cancer
Popis: 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.
Databáze: OpenAIRE
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