Advanced malignancies treated with a combination of the VEGF inhibitor bevacizumab, anti-EGFR antibody cetuximab, and the mTOR inhibitor temsirolimus
Year: 2016
Type: article
Study design: Clinical Trial
Abstract: // Xiaochun Liu 1 , Susan Kambrick 1 , Siqing Fu 1 , Aung Naing 1 , Vivek Subbiah 1 , George R. Blumenschein 2 , Bonnie S. Glisson 2 , Merrill S. Kies 2 , Apostolia M. Tsimberidou 1 , Jennifer J. Wheler 1 , Ralph G. Zinner 1 , David S. Hong 1 , Razelle Kurzrock 3 and Sarina A. Piha-Paul 1 1 Department of Investigational Cancer Therapeutics, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Thoracic/Head & Neck Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA 3 Division of Hematology and Oncology, University of California San Diego, Moores Cancer Center, San Diego, CA, USA Correspondence to: Sarina A. Piha-Paul, email: // Keywords : solid tumors, bevacizumab, cetuximab, temsirolimus Received : August 20, 2015 Accepted : February 05, 2016 Published : February 24, 2016 Abstract BACKGROUND: Bevacizumab and temsirolimus are active agents in advanced solid tumors. Temsirolimus inhibits mTOR in the PI3 kinase/AKT/mTOR pathway as well as CYP2A, which may be a resistance mechanism for cetuximab. In addition, temsirolimus attenuates upregulation of HIF-1α levels, which may be a resistance mechanism for bevacizumab. RESULTS: The median age of patients was 60 years (range, 23-80 years). The median number of prior systemic therapies was 3 (range, 1-6). The maximum tolerated dose (MTD) was determined to be bevacizumab 10 mg/kg biweekly, temsirolimus 5 mg weekly and cetuximab 100/75 mg/m2 weekly. Grade 3 or 4 toxicities were seen in 52% of patients with the highest prevalence being hyperglycemia (14%) and hypophosphatemia (14%). Eighteen of the 21 patients were evaluable for response. Three patients were taken off the study before restaging for toxicities. Partial response (PR) was observed in 2/18 patients (11%) and stable disease (SD) lasting ≥ 6 months was observed in 4/18 patients (22%) (total = 6/18 (33%)). In 8 evaluable patients with squamous cell carcinoma of the head and neck (HNSCC) there were partial responses in 2/8 (25%) patients and SD ≥ 6 months in 1/8 (13%) patients (total = 3/8, (38%)). PATIENTS AND METHODS: We analyzed safety and responses in 21 patients with advanced solid tumors treated with bevacizumab, cetuximab, and temsirolimus. CONCLUSION: The combination of bevacizumab, cetuximab, and temsirolimus showed activity in HNSCC; however, there were numerous toxicities reported, which will require careful management for future clinical development.
Source: Oncotarget
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2292413078