A phase I trial of azacitidine and nanoparticle albumin bound paclitaxel in patients with advanced or metastatic solid tumors
| Autor: | Abhijit Ray, Matthew Van Brocklin, Adam L. Cohen, Hung T. Khong, Donna Lynn Dyess, Thomas W. Butler, Randy C. Bowen, Theresa Liu Dumlao, David M. Burnett |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty azacitidine Huntsman Cancer Institute Azacitidine 03 medical and health sciences chemistry.chemical_compound nab-paclitaxel 0302 clinical medicine Breast cancer Internal medicine medicine phase I clinical trials business.industry Endometrial cancer Cancer SPARC medicine.disease Surgery Regimen 030104 developmental biology Paclitaxel chemistry 030220 oncology & carcinogenesis solid tumor Ovarian cancer business medicine.drug Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Adam L. Cohen 1, * , Abhijit Ray 2, * , Matthew Van Brocklin 3 , David M. Burnett 3 , Randy C. Bowen 4 , Donna L. Dyess 5 , Thomas W. Butler 5 , Theresa Dumlao 6 and Hung T. Khong 1 1 Department of Medicine, Division of Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA 2 Division of Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA 3 Department of Surgery, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA 4 Department of Medicine, University of Utah, Salt Lake City, UT, USA 5 University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA 6 Banner MD Anderson Cancer Center, Gilbert, AZ, USA * These authors have contributed equally to this work Correspondence to: Hung T. Khong, email: hung.khong@hci.utah.edu Keywords: nab-paclitaxel, azacitidine, solid tumor, phase I clinical trials, SPARC Received: August 19, 2016 Accepted: November 18, 2016 Published: December 26, 2016 ABSTRACT Background: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel. Methods: Patients received escalating azacytidine doses daily for 5 days, followed by nab-paclitaxel at the standard 100mg/m2 weekly dose for 3 weeks in 4-week cycles. Dose-limiting toxicities (DLTs) were monitored during the first cycle. Serum was obtained at baseline, during and after treatment for correlative study. Results: All sixteen total patients enrolled were evaluable for toxicity, while 13 patients were evaluable for response. Two of five patients treated with 100mg/m2 of azacytidine had DLT of prolonged grade 4 neutropenia. Therefore, the MTD of azacitidine in this regimen is 75 mg/m 2 . Three additional patients were treated with no grade 4 toxicity in cycle 1. Clinical activity included 1 complete response (CR) in refractory DLBCL, 2 CR in ovarian cancer, 4 partial responses (PR) in ovarian and endometrial cancer, 4 stable diseases (SD) in lung, sarcoma and pancreatic cancer, 1 unconfirmed PR in breast cancer, and 1 progression of disease in CLL/SLL. Conclusions: Priming with azacitidine 75 mg/m 2 daily for 5 days, followed by weekly nab-paclitaxel 100 mg/m 2 weekly was well tolerated and results in dramatic responses pre-treated cancer patients. |
| Databáze: | OpenAIRE |
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