Randomized Control Trial of Addition of Aspirin to Standard Care in Oral Cancer Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
Despite accumulating evidence of the benefit of aspirin in cancer, its effect on improving cancer survival is still debated since the mechanism by which it impacts cancer survival is not completely understood and the published data are discordant. There have been 4 randomized controlled trials (RCT) showing mixed results from no effect to improved survival. Several retrospective and observational studies have reported a survival advantage of adding aspirin to the treatment for various cancers. A meta-analysis of 118 studies, 63 of them specifically reporting on cancer mortality and the rest on all-cause mortality, found a 21% reduction in cancer deaths and about 20% reduction in all-cause mortality (pooled hazard ratio (HR): 0.79; 95% confidence intervals: 0.73, 0.84).
However, the evidence is still lacking and there is need to do more RCT
详细描述
Aspirin (ASA), an NSAID, is a well-known antipyretic and analgesic agent and is used to prevent recurrent transient ischemic attacks or strokes. In addition to its classical anti- inflammatory function, clinical and epidemiological studies indicate that aspirin can be used as a preventive or therapeutic agent in multiple cancers, including oral cancers
While the exact mechanism through which NSAIDs contribute to chemo prevention is not completely understood, Aspirin inhibits the enzyme Cox; Cox-1 and Cox-2 are well characterized. Cox converts a arachidonic acid to prostaglandin H2, which in turn produces biologically active prostaglandins that influence path physiological processes in a range of tissues including angiogenesis, apoptosis, cell proliferation and migration, inflammatory response and thrombosis. Inhibition of prostaglandin synthesis is considered the pre dominant mechanism by which NSAIDs act as anti-inflammatory agents, but it is unclear whether the anti-cancer properties of these agents can be solely attributed to Cox inhibition.
Recently, Cox-2 over expression has been identified in a number of different malignancies and it has been hypothesized that Cox-2 prostaglandins promote tumor genesis by inhibiting apoptosis, modulating the immune system and regulating tumor associated angiogenesis.
A detailed search of literature and bio informatics analysis of the data obtained showed that the effect of Aspirin on survival and prevention of recurrence and secondary cancer could be due to its effect on following 11 genes PTGS2, PIK3CA, PARP1, PARP2, VEGFA, KDR, PTGES2, NFKB1, P53, FLT1, VEGFR. These genes not only interact and control each other but also control cell cycle regulation through other genes as shown below. These could be due to co expression, physical interactions, shared domains or predicted interactions in absence of data.
Based on the gene-gene and protein-protein interactions they can be clustered into three with PTGES2, PTGS2 and p53 being in first cluster (figure 2 below), the NGS data obtained from the previous patients also showed the p53 to be the primary driver gene (unpublished data, submitted) in nearly 50% of the subjects. It has also been shown that patients with p53 mutations
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All Histologically proven cases of primary oral cancers.
- •Stage T1 to T4, N0 to N3, M0 to M
- •Age above
- •Karnofsky' performance status more than 70, ECOG 0 to 2
- •Hb >8.0 gm/dL
- •Total count >4000 cu mm
- •Platelet count >100000 Serum creatinine <1.0mg
- •Liver enzymes up to 1.5 times normal
- •Bilirubin <1.0mg
排除标准
- •Patients with acid peptic disease
- •Pregnant and lactating women.
- •Patients not willing to participate.
- •Patients with known allergy to NSAID
- •Patients with Asthma, rhinitis and nasal polyps
- •Presence of viral fever
- •Use of any other blood thinner like warfarin, heparin or low molecular weight heparin
- •bleeding/blood-clotting disorders (such as hemophilia, vitamin K deficiency, low platelet count)
- •pyruvate kinase or G6PD deficiency
- •Patients receiving mifepristone, acetazolamide, corticosteroids, dichlorphenamide, methotrexate, valproic acid, herbal medications (such as ginkgo biloba)
- •Patients with recent history of anti-viral vaccines
研究组 & 干预措施
Interventional arm
Aspirin 150mg PO daily along with standard of care
干预措施: Aspirin 150 mg (Drug)
Standard of care
Standard of care as per the stage of disease and guidelines i.e. Surgery, Surgery with radiation or palliative chemotherapy as per investigators choice
干预措施: Standard of care (Procedure)
结局指标
主要结局
Adverse events
时间窗: 4 weeks
Number of participants with treatment-related adverse events as assessed by WHO toxicity criteria
次要结局
- Disease free survival(through study completion, an average of 2 year)
- Overall survival(through study completion, an average of 2 year)
研究者
Manoj Pandey
Professor
Banaras Hindu University