In three combined drugs used in nasopharyngeal carcinoma, the valproic acid and valganciclovir administration will be followed by indication to find the maximum tolerance dose of gemcitabine.

Nasopharyngeal Carcinoma

Gemcitabine will be administrated 600~1250 mg/m^2 intravenously according to the body surface area at day 1 and day 8 in a 28 day-treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times. The first dose level of gemcitabine will be started at 800 mg/m^2. If no subject suffered the dose limit toxicity, 1000 mg/m^2 and even 1250 mg/m^2 will be started by order. If subjects suffered the dose limit toxicity in 800 mg/m^2, the 600 mg/m^2 will be started.

Gemcitabine

Valproic acid will be administrated orally by the fixed dose 12.5 mg/kg/day according to instructions from day 1 to day 14 in one treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times.

Valproic acid

Valganciclovir will be administrated orally by the fixed dose 1350 mg/day (creatinine clearance rate ≥ 60 mL/min) or 900 mg/day (creatinine clearance rate ≥ 40 mL/min and < 60 mL/min) from day 9 to day 15 in one treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times.

Valganciclovir

Chang-Gung Memorial Hospital, Linkou

Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

Phase I Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

According to Worst Toxicity CTCAE v4.03 Grade and FDA indication of gemcitabine, the dose limiting toxicity (DLT) of this trial was determined in the first treatment cycle and DLTs were defined as ≥1 of the following effects attributable to the study drug and requiring discontinuation or a significant dose reduction in the study drug(s):
≥Grade 4 neutropenia >5 days;
≥Grade 4 thrombopenia lasting ≥7 days;
≥Grade 3 anemia;
≥Grade 3 neutropenic fever with a single temperature of >38.3 degree C or a sustained temperature of ≥ 38 degree C for more than one hour;
any ≥Grade 3 non-hematologic toxicity with exception of nausea and vomiting, alopecia, drug-related fever;
≥Grade 3 serum creatinine;
bone marrow and renal function didn't recover to CTCAE Grade ≤ 1 of baseline at the Day 1 of the 2nd treatment course, the treatment can be postponed less than 2 weeks. DLT was recognized when the delayed duration was more than 2 weeks.

The plasma EB virus DNA load will be check by real-time quantitative polymerase chain reaction (PCR). These data will be collected every months when subjects enter this trial and finish their final treatment cycle one weeks, 3 months, and/or 6 months later. These data will be used to supplementary data for tumor status assessment.

Chang Gung Memorial Hospital

TTY Biopharm

administer dexmedetomidine (0.1-0.7ug/kg/h) from the beginning of ICU treatment

administer sedatives except Dexmedetomidine

Sepsis

intervention to administer dexmedetomidine or not

Dexmedetomidine

Tohoku University

Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial

Effect of Dexmedetomidine on Mortality, Duration of Mechanical Ventilation and Multi-organ Function in Sepsis Patients Under Lighter Sedation by Randomized Control Trial

mortality of patients on 28 days or on a day of discharge if patients are discharged earlier than 28 days

duration of mechanical ventilation in the ICU involving non-invasive ventilation

evaluation of Richmond agitation-sedation scale (RASS) and Confusion Assessment Method for ICU patients (CAM-ICU)

evaluation of Mini mental state examination (MMSE) on the 28 days or on a day of discharge if patients are discharged earlier than 28 days

blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), daily urinary output, need of renal replacement therapy

Duration of antimicrobial agents use within 28 days or a day of discharge if patients are discharged earlier than 28 days

Laboratory marker of inflammation (CRP, PCT) on 1,3,7,14 days

Sequential Organ Failure Assessment (SOFA) score during in the ICU

Disseminated Intravascular Coagulation (DIC) score by the Japanese Association for Acute Medicine during in the ICU

aminobutyrate/krabbamein

Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial

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