Research Papers:

A phase I trial of azacitidine and nanoparticle albumin bound paclitaxel in patients with advanced or metastatic solid tumors

Adam L. Cohen _, Abhijit Ray, Matthew Van Brocklin, David M. Burnett, Randy C. Bowen, Donna L. Dyess, Thomas W. Butler, Theresa Dumlao and Hung T. Khong

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Oncotarget. 2017; 8:52413-52419. https://doi.org/10.18632/oncotarget.14183

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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

Correspondence to:

Hung T. Khong, email: [email protected]

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.

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