Metabolic Responses to Metformin in Inoperable Early-stage Non-Small Cell Lung Cancer Treated With Stereotactic Radiotherapy Results of a Randomized Phase II Clinical Trial

被引:14
作者
Chun, Stephen G. [1 ]
Liao, Zhongxing [1 ]
Jeter, Melenda D. [1 ]
Chang, Joe Y. [1 ]
Lin, Steven H. [1 ]
Komaki, Ritsuko U. [4 ]
Guerrero, Thomas M. [5 ]
Mayo, Ray C. [2 ]
Korah, Bobby M. [1 ]
Koshy, Suja M. [1 ]
Heymach, John, V [3 ]
Koong, Albert C. [1 ]
Skinner, Heath D. [1 ,6 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Div Radiat Oncol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Radiat Oncol, Houston, TX 77030 USA
[5] William Beaumont Sch Med, Dept Radiat Oncol, Royal Oak, MI USA
[6] Univ Pittsburgh, Dept Radiat Oncol, 200 Lothrop St, Pittsburgh, PA 15213 USA
来源
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS | 2020年 / 43卷 / 04期
关键词
SBRT; NSCLC; metformin; PET scan;
D O I
10.1097/COC.0000000000000632
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Metformin reduces glucose uptake in physiologic tissues and has been shown to affect non-small cell lung cancer (NSCLC) metabolism. We hypothesized that positron emission tomography (PET) scans could detect the impact of metformin on glucose uptake in NSCLC and we sought to test this hypothesis in a prospective clinical trial. Materials and Methods: A single-blinded phase II clinical trial was performed with subjects randomized 6:1 to 3 to 4 weeks of metformin versus placebo for inoperable early-stage NSCLC. PET scans were performed at baseline, mid-treatment (after 2 wk study medication), and 6 months postradiation. The primary endpoint of the trial was tumor metabolic response to metformin by PERCIST before definitive radiation. Stereotactic body radiotherapy to 50 Gy in 4 fractions was used for peripheral tumors and 70 Gy in 10 fractions for central tumors. Results: There were 14 subjects randomized to the metformin and 1 to placebo. Histologies were 60% adenocarcinoma, 33.3% squamous cell carcinoma, and 6.7% poorly differentiated carcinoma. At mid-treatment PET scan, 57% of subjects randomized to metformin met PERCIST criteria for metabolic response, of which 75% had progressive metabolic disease and 25% had partial metabolic response, whereas the placebo subject had stable metabolic disease. At 6 months, the metformin arm had 69% complete metabolic response, 23% partial metabolic response and 1 progressive metabolic disease, and the subject treated with placebo had a complete metabolic response. There were no CTCAE grade >= 3 toxicities. Conclusions: Despite low accrual, majority of subjects treated with metformin had metabolic responses by PERCIST criteria on PET imaging. Contrary to the effect of metformin on most physiologic tissues, most tumors had increased metabolic activity in response to metformin.
引用
收藏
页码:231 / 235
页数:5
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