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• W2994990079 abstract "Abstract Background Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3–18 years) with relapsed or therapy-refractory malignancies. Results A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m 2 /day with weekly dose escalations of 50 mg/m 2 until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m 2 /day was determined (maximum, 580 mg/m 2 /day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher C max . Five patients achieved prolonged disease control (> 12 months) and showed a higher C max (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome. Conclusion An SDR of 130 mg/m 2 /day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker. Trial registration ClinicalTrials.gov, NCT01422499 . Registered 24 August 2011," @default.
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• W2994990079 date "2019-12-01" @default.
• W2994990079 modified "2023-10-14" @default.
• W2994990079 title "Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia" @default.
• W2994990079 cites W1516453481 @default.
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• W2994990079 cites W1905474624 @default.
• W2994990079 cites W1964372470 @default.
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• W2994990079 cites W1992392607 @default.
• W2994990079 cites W1993916129 @default.
• W2994990079 cites W1995364339 @default.
• W2994990079 cites W2019607817 @default.
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• W2994990079 cites W2026646891 @default.
• W2994990079 cites W2026861011 @default.
• W2994990079 cites W2028896946 @default.
• W2994990079 cites W2052702202 @default.
• W2994990079 cites W2057358066 @default.
• W2994990079 cites W2065381425 @default.
• W2994990079 cites W2069412671 @default.
• W2994990079 cites W2086384126 @default.
• W2994990079 cites W2096398040 @default.
• W2994990079 cites W2097946365 @default.
• W2994990079 cites W2101546733 @default.
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• W2994990079 cites W2112309180 @default.
• W2994990079 cites W2126085546 @default.
• W2994990079 cites W2128783106 @default.
• W2994990079 cites W2135619784 @default.
• W2994990079 cites W2137591261 @default.
• W2994990079 cites W2139248078 @default.
• W2994990079 cites W2149860981 @default.
• W2994990079 cites W2167597760 @default.
• W2994990079 cites W2207035666 @default.
• W2994990079 cites W2270022990 @default.
• W2994990079 cites W2300908044 @default.
• W2994990079 cites W2333348230 @default.
• W2994990079 cites W2403288812 @default.
• W2994990079 cites W2475853404 @default.
• W2994990079 cites W2589656556 @default.
• W2994990079 cites W2603517011 @default.
• W2994990079 cites W2616094199 @default.
• W2994990079 cites W2724336500 @default.
• W2994990079 cites W2787816121 @default.
• W2994990079 cites W2794690006 @default.
• W2994990079 cites W2802705550 @default.
• W2994990079 cites W2890578922 @default.
• W2994990079 cites W2890660292 @default.
• W2994990079 cites W2891839100 @default.
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• W2994990079 doi "https://doi.org/10.1186/s13148-019-0775-1" @default.
• W2994990079 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6902473" @default.
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