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["Table 2. Findings of the including studies."]
["Author-year","Study design","Groups (N)","Outcomes（intervention）","Adverse events"]
["Patil-2020[17]","open-label, parallel-group, non-inferiority, randomized, phase 3 trial","Intervention (213): 15 mg/m² methotrexate once per week + 200 mg celecoxib twice per day;\nControl (209): 75 mg/m² intravenous cisplatin once every 3 weeks for six cycles","Intervention: \nMedian OS: 7.5 months\nMedian PFS: 3·23 months \nunadjusted HR for death: 0.773 (95%CI 0.615-0.970, p=0·026)\nunadjusted HR for PFS: 0·511 (95%CI 0.414-0.630, p<0·0001)\nControl: \nMedian OS: 6.1 months \nMedian PFS:  1·63 months \nno differences in QLQ-C30 functional scores and QLQ-H&N35 symptom scores between the two groups","Intervention: \nAdverse events: 178 (91%)\nGrade 3 or higher adverse events: 37 (19%) \nprogression events: 172 \nlocoregional site: 152 (88%) \ndistant site: 14 (8%) \nboth sites: 6 (3%)\nControl: \nAdverse events: 189 (94%) (p=0·352)\nGrade 3 or higher adverse events: 61 (30%) (p=0·01)\nprogression events: 192\nlocoregional site: 174 (91%) \ndistant site: 7 (4%) \nboth sites: 11 (6%) "]
["Swiecicki-2016[18]","a phase 2, three-arm, randomized, open label trial","Intervention (11): docetaxel (75 mg/m2 every 21 days) + metronomic AT-101 (20 mg daily, days 1-14) ;\nControl (11): docetaxel (75 mg/m2 every 21 days) + pulse dose AT101 (40mg B.I.D, 3 days)","Reported the outcome of entire cohort:  Median PFS: 4.3 months\nMedian OS: 5.5 months","Hematologic toxicities were the most common treatment related toxicities. No differences in treatment tolerability or toxicities were grossly apparent."]
["Patil-2015[19]","an open label, superiority, parallel design, randomized phase II trial","Intervention (57): daily oral celecoxib 200 mg twice daily and oral low dose methotrexate 15mg/m2 weekly;\nControl (53): 3-weekly cisplatin 75 mg/m2 for a maximum of 6 cycles","Intervention: \nMedian PFS: 101 days\nMedian OS: 249 days \nHR for PFS: 0.63 (95% CI 0.42–0.91)\nHR for OS: 0.61 (95%CI 0.40–0.95)\nControl: \nMedian PFS: 66 days (p= 0.014)\nMedian OS: 152 days (p = 0.02)","There is no toxicity related death in both arms. The most common side effects are anaemia, weakness and mucositis in metronomic chemotherapy group and anaemia, weakness and hyponatremia in cisplatin group."]
["Lin-2015[20]","Cohort study (trail)","Intervention (40): orally administered UFUR 4 weeks at a dose of 150 mg/m2/d, twice daily for 12 months;\nControl (40): No treatment","Intervention:\nSurvival rates: 84.6% at 4 years\nHR for survival: 0.78 (95%CI 0.57-0.98, P=0.04)\nControl:\nSurvival rates: 60.9% at 4 years (P = 0.02)","Adverse events including anemia, nausea and vomiting, erythematous skin rash did not differ significantly from two groups."]
["Patil-2019[21]","single-arm study","erlotinib 150 mg once per day, celecoxib 200 mg twice per day, and methotrexate 9 mg/m2 per week.","Median PFS: 4.6 months \nMedian OS: 7.17 months\nHR for PFS：0.988 ( 95% CI 0.980-0.997，P=0.007)\nHR for death: 0.985 (95% CI, 0.974-0.996, P=0.009)","Locoregional site: 50 \nDistant site: 1 \nBoth site: 6 \nThe most common adverse events of any grade were fatigue, rash, anemia. Grade 3 to 4 adverse events are hyponatremia and ALT."]
["Patil-2017[24]","match pair analysis of a prospectively maintained database","Intervention (60): oral weekly methotrexate at a dose of 15 mg/m2 along with capsule celecoxib 200 mg orally twice daily;\nControl (60): weekly paclitaxel (80 mg/m2) along with weekly cetuximab (loading dose of 400 mg/m2 followed by 250 mg/m2)","Total:\nMedian OS: 249 days\nIntervention:\nMedian PFS:  101 days \nMedian OS: 191 days \nControl:\nMedian PFS: 173 days\nMedian OS: 256 days\nHR for PFS: 0.58 (95%CI: 0.38–0.91, P = 0.016)\nHR for OS: 0.58 (95% CI: 0.35–0.95, P = 0.031)\nThe response: 16 patients (P = 0.002)\nClinical benefit rate (5 months): 45 patients (P = 0.000)","Intervention (3):\nPneumonia: 1 patient\nOral mucositis: 2 patients\nControl (8):\nSevere toxicity: 3\nSensory neuropathy: 4\nSevere rash: 1"]
["Lee-2017[22]","a prospective phase II single-arm open-label study","oral cyclophosphamide between 50 and 150mg once daily","Median PFS: 4.47 months \nMedian OS: 9.20 months\nthe median cost: 25.77 USD (range 4.15–142.75)","Adverse events (34): \nGrade ≥3: 16 patients \nGrade 3 or higher adverse events included malaise, hematological, gastrointestinal, feverish, hemorrhagic."]
["Patil-2016[23]","A single-arm prospective observational study","Oral methotrexate (15 mg/m2/week), oral celecoxib (200 mg twice daily), and erlotinib (150 mg once daily)","Median PFS: 148 days\nMedian OS cannot be calculated because there were only three death.\nComplete remission: 2 patients \nPartial remission: 7 patients\nStable disease: 4 patients","Progression: 9 patients\nThe grade 3–4 toxicity happened in 6 patients. But mortality due to toxicity was seen in no patient."]
["Patil-2017[25]","a retrospective analysis of database","Oral a combination of celecoxib (200 mg BD) and methotrexate (15 mg/m2 weekly)","Median PFS: 101 days \nMedian OS: 249 days \nThe median OS was different in different subsites in head and neck cancer.","Data regarding toxicity and compliance were not available in this study."]
["Rohit-2017[26]","retrospective study","chemotherapeutic agents (including Taxols, Platins, 5-Fluorouracil and Epidermal Growth Factor Receptor inhibitors) at approximate 50% dose of currently recommended doses","Median PFS: 14.0 months \nMedian OS: 15.7 months","Progressive disease: 11\nhigh-grade toxicities were as follows:\ngeneralized fatigue: 4 patients\nneutropenia (grade 3): 6 patients\nneutropenia (grade 4): 1 patient"]
["Pandey-2016[27]","a retrospective study","methotrexate (15 mg/m2) once a week and capsule celecoxib 200 mg twice daily for a period of 18 months","Median DFS: 13 months\nMedian OS: 30 months","Data regarding toxicity and compliance were not available in this study."]
["Pai-2013[28]","a retrospective analysis","oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily","Intervention (32): \nComplete response: 2 \nPartial response: 22 \nResponse rate: 75%\nStable disease: 8 \nEstimated two-year DFS: 94.6% (log rank test, P = 0.03)\nControl (32):\nEstimated two-year DFS: 75.4%","Intervention:\nRecurrences: 4 patients (median follow-up: 19 months)\nControl:\nRecurrences: 9 patients \nThere were no major toxicity cases."]
["Patil-2012[29]","Retrospective analysis of prospectively collected data","oral celecoxib 200 mg twice daily + weekly oral low dose methotrexate 15 mg/m2","Median PFS: 5 months\nMedian OS: 3.05 months ","progression of disease: 9\ngrade 4 (mucositis): 1 patient \ngrade 1 or grade 2 (mucositis): 12 patients\ngrade 3 (anemia): 1 patient"]
["OS: Overall survival; PFS: Progression free survival; DFS: Disease free survival."]