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Oncotarget. 2016 Jul 5;7(27):42625-42638. doi: 10.18632/oncotarget.9434.

Phase I study of pemetrexed with sorafenib in advanced solid tumors.

Author information

1
Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
2
Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
3
Current address: Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
4
Current address: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
Departments of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA.
6
Departments of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA.
7
Departments of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA.
8
Departments of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.

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.

KEYWORDS:

clinical trial; pemetrexed; solid tumors; sorafenib

PMID:
27213589
PMCID:
PMC5173162
DOI:
10.18632/oncotarget.9434
[Indexed for MEDLINE]
Free PMC Article

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