***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Altered histone deacetylase ( HDAC ) activity has been identified in several types of cancer . This study was design ed to determine the safety and maximum tolerated dose ( MTD ) of valproic acid ( VPA ) as an HDAC inhibitor in cancer patients . Twenty-six pre-treated patients with progressing solid tumours were enrolled in dose-escalating three-patient cohorts , starting at a dose of VPA 30 mg kg−1 day−1 . VPA was administered as an 1-h infusion daily for 5 consecutive days in a 21-day cycle . Neurocognitive impairment dominated the toxicity profile , with grade 3 or 4 neurological side effects occurring in 8 out of 26 patients . No grade 3 or 4 haematological toxicity was observed . The MTD of infusional VPA was 60 mg kg−1 day−1 . Biomonitoring of peripheral blood lymphocytes demonstrated the induction of histone hyperacetylation in the majority of patients and downmodulation of HDAC2 . Pharmacokinetic studies showed increased mean and maximum serum VPA concentrations > 120 and > 250 mg l−1 , respectively , in the 90 and 120 mg kg−1 cohorts , correlating well with the incidence of dose-limiting toxicity ( DLT ) . Neurotoxicity was the main DLT of infusional VPA , doses up to 60 mg kg−1 day−1 for 5 consecutive days are well tolerated and show detectable biological activity . Further investigations are warranted to evaluate the effectivity of VPA alone and in combination with other cytotoxic drugs We explored in a phase I/II clinical trial the combination of valproic acid ( VPA ) , a clinical ly available histone deacetylase inhibitor , with st and ard chemoimmunotherapy in patients with advanced melanoma , to evaluate its clinical activity , to correlate the clinical response with the biological activity of VPA and to assess toxicity . Patients were treated initially with VPA alone for 6 weeks . The inhibition of the target in non-tumour peripheral blood cells ( taken as a potential surrogate marker ) was measured periodically , and valproate dosing adjusted with the attempt to reach a measurable inhibition . After the treatment with valproate alone , dacarbazine plus interferon-α was started in combination with valproate .  Twenty-nine eligible patients started taking valproate and 18 received chemoimmunotherapy and are assessable for response . We observed one complete response , two partial remissions and three disease stabilisations lasting longer than 24 weeks . With the higher valproate dosages needed to reach a measurable inhibition of the target , we observed an increase of side effects in those patients who received chemoimmunotherapy . The combination of VPA and chemoimmunotherapy did not produce results overtly superior to st and ard therapy in patients with advanced melanoma and toxicity was not negligible , casting some doubts on the clinical use of VPA in this setting ( at least in the administration schedule adopted ) 
    Output:
    
The results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration .
Sub- analysis confirmed the benefit of VPA use compared to a non-AEDs group and an other-AEDs group .