Oncotarget

Clinical Research Papers:

Phase I study of pemetrexed with sorafenib in advanced solid tumors

Andrew Poklepovic, _ Sarah Gordon, Danielle A. Shafer, John D. Roberts, Prithviraj Bose, Charles E. Geyer Jr, William P. McGuire, Mary Beth Tombes, Ellen Shrader, Katie Strickler, Maria Quigley, Wen Wan, Maciej Kmieciak, H. Davis Massey, Laurence Booth, Richard G. Moran, Paul Dent

PDF |  HTML  |  Author Information  |  Order a Reprint

 

Metrics: PDF 415 views  |   HTML 236 views  |   ?  

here


Abstract

Andrew Poklepovic1,2, Sarah Gordon2, Danielle A. Shafer1,2, John D. Roberts1,2,7, Prithviraj Bose1,2,8, Charles E. Geyer Jr.1,2, William P. McGuire1,2, Mary Beth Tombes1, Ellen Shrader1, Katie Strickler1, Maria Quigley1, Wen Wan1,3, Maciej Kmieciak1, H. Davis Massey4, Laurence Booth5, Richard G. Moran1,6, Paul Dent1,5

1Department of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA

2Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

3Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA

4Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA

5Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA

6Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA

7Current address: Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA

8Current address: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Correspondence to:

Andrew Poklepovic, email: andrew.poklepovic@vcuhealth.org

Keywords: clinical trial, pemetrexed, solid tumors, sorafenib

Received: February 26, 2016     Accepted: April 16, 2016     Published: May 18, 2016

ABSTRACT

Purpose: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors.

Results: Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable. The maximum tolerated dose (MTD) was pemetrexed 750 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1–5. Because dosing delays and modifications were associated with the MTD, the recommended phase II dose was declared to be pemetrexed 500 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1–5. Thirty-three patients were evaluated for antitumor activity. One complete response and 4 partial responses were observed (15% overall response rate). Stable disease was seen in 15 patients (45%). Four patients had a continued response at 6 months, including 2 of 5 patients with triple-negative breast cancer.

Experimental Design: A phase I trial employing a standard 3 + 3 design was conducted in patients with advanced solid tumors. Cohort A involved a novel dose escalation schema exploring doses of pemetrexed every 14 days with continuous sorafenib. Cohort B involved a modified schedule of sorafenib dosing on days 1–5 of each 14-day pemetrexed cycle. Radiographic assessments were conducted every 8 weeks.

Conclusions: Pemetrexed and intermittent sorafenib therapy is a safe and tolerable combination for patients, with promising activity seen in patients with breast cancer.

Author Information

Andrew Poklepovic
Primary Contact  _

Sarah Gordon

Danielle A. Shafer

John D. Roberts

Prithviraj Bose

Charles E. Geyer Jr

William P. McGuire

Mary Beth Tombes

Ellen Shrader

Katie Strickler

Maria Quigley

Wen Wan

Maciej Kmieciak

H. Davis Massey

Laurence Booth

Richard G. Moran

Paul Dent


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 9434