A phase I trial of azacitidine and nanoparticle albumin bound paclitaxel in patients with advanced or metastatic solid tumors
Metrics: PDF 1738 views | HTML 1882 views | ?
Adam L. Cohen1,*, Abhijit Ray2,*, Matthew Van Brocklin3, David M. Burnett3, Randy C. Bowen4, Donna L. Dyess5, Thomas W. Butler5, Theresa Dumlao6 and Hung T. Khong1
1Department of Medicine, Division of Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
2Division of Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
3Department of Surgery, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
4Department of Medicine, University of Utah, Salt Lake City, UT, USA
5University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA
6Banner MD Anderson Cancer Center, Gilbert, AZ, USA
*These authors have contributed equally to this work
Hung T. Khong, email: email@example.com
Keywords: nab-paclitaxel, azacitidine, solid tumor, phase I clinical trials, SPARC
Received: August 19, 2016 Accepted: November 18, 2016 Published: December 26, 2016
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/m2. 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/m2 daily for 5 days, followed by weekly nab-paclitaxel 100 mg/m2 weekly was well tolerated and results in dramatic responses pre-treated cancer patients.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.