Department of Radiation Oncology, Division of Radiation Oncology.
Department of Radiation Oncology, Baylor College of Medicine, Houston, TX.
Am J Clin Oncol. 2020 Apr;43(4):231-235. doi: 10.1097/COC.0000000000000632.
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.
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.
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.
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.
二甲双胍可降低生理组织对葡萄糖的摄取，已被证实会影响非小细胞肺癌（NSCLC）的代谢。我们假设正电子发射断层扫描（PET）可检测二甲双胍对 NSCLC 葡萄糖摄取的影响，并在一项前瞻性临床试验中对此假说进行了检验。
采用单盲 II 期临床试验，将受试者随机分为 6:1 至 3:4 组，分别接受 3 至 4 周的二甲双胍或安慰剂治疗，用于治疗不可手术的早期 NSCLC。在基线、治疗中期（研究药物治疗 2 周后）和放疗后 6 个月进行 PET 扫描。试验的主要终点是在接受确定性放疗前，根据 PERCIST 标准评估肿瘤对二甲双胍的代谢反应。采用立体定向体部放疗，外周肿瘤剂量为 50 Gy/4 次，中心肿瘤剂量为 70 Gy/10 次。
共有 14 例受试者被随机分配至二甲双胍组，1 例受试者被分配至安慰剂组。组织学类型为 60%腺癌、33.3%鳞状细胞癌和 6.7%低分化癌。在治疗中期 PET 扫描时，57%随机分配至二甲双胍组的受试者符合 PERCIST 代谢反应标准，其中 75%为进展性代谢疾病，25%为部分代谢反应，而安慰剂组受试者为稳定的代谢疾病。在 6 个月时，二甲双胍组有 69%完全代谢反应、23%部分代谢反应和 1 例进展性代谢疾病，而接受安慰剂治疗的受试者有完全代谢反应。无 CTCAE 分级≥3 级毒性反应。
尽管入组人数较少，但大多数接受二甲双胍治疗的受试者在 PET 成像上根据 PERCIST 标准显示代谢反应。与二甲双胍对大多数生理组织的作用相反，大多数肿瘤对二甲双胍的反应是代谢活性增加。
