Ramadori, Giuliano

[["dc.bibliographiccitation.firstpage","632"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Therapeutic Drug Monitoring"],["dc.bibliographiccitation.lastpage","643"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Hafke, Angelika"],["dc.contributor.author","Brandhorst, Gunnar"],["dc.contributor.author","Braulke, Friederike"],["dc.contributor.author","Haase, Detlef"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Oellerich, Michael"],["dc.contributor.author","Walson, Philip D."],["dc.date.accessioned","2018-11-07T08:51:25Z"],["dc.date.available","2018-11-07T08:51:25Z"],["dc.date.issued","2011"],["dc.description.abstract","Objectives: Trough total imatinib (t-IM) concentrations have been reported to be associated with therapeutic and toxic responses in patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST). Little is known about the relationships between effects and concentrations of either unbound imatinib (f-IM) or imatinib's major metabolite, N-desmethyl imatinib (NDI). In part, this is because of the lack of a single, validated, well-described clinically useful assay for these measurements. The authors report the development and application of such an assay. Materials and Methods: A single liquid-chromatography tandem-mass-spectrometry assay was used to monitor t-IM, f-IM, and t-NDI concentrations in CML and GIST patients treated at a tertiary German teaching hospital. The assay was also validated for measuring other kinase inhibitors, including t-nilotinib, sunitinib, and erlotinib. Ultrafiltration assays were validated and used to measure f-IM and to compare free fractions to plasma alpha(1)-acid glycoprotein concentrations (AGP). Results: The assays were linear over a working range (in micrograms per liter) of 8.4-8370, 8.3-4165, and 1.0-250 and had within-and between-run coefficient of variance of <7%, <12%, and <9% for t-IM, t-NDI, and f-IM, respectively. The f-IM assay was reproducible despite high (25.2%-31.6%) but concentration-independent binding to ultrafiltration devices. Clinically relevant results, such as nondetectable (ND) t-IM (<8.4 mu g/L) in non-responders and >1500 mu g/L in patients with major toxicity, were found. Of 156 total samples from 68 adult CML patients and 127 total samples from 42 adult GIST, only 48 samples from 22 CML patients and 40 samples from 20 GIST patients were trough samples with adequate dosing and collection information. More than half (27 of 48 CML and 24 of 40 GIST) had t-IM concentrations >= 10% below recommended target concentrations (1002 mu g/L for CML and 1100 mu g/L for GIST). Concentrations.50% over targets were also found in 6 of 48 CML and 4 of 40 GIST samples. Wide variations in concentrations of t-IM (range, ND to 2973 mu g/L), t-NDI (range, ND to 659 mu g/L), f-IM (range, 8.3-262 mu g/L), and t-IM:f-IM ratios (range, 2.6%-14%) were found both between and within patients. A statistically significant association (Spearman correlation coefficient and P value for all samples, r = 0.290 and P = 0.023; for trough only, r = -0.585 and P = 0.028) was found between AGP and f-IM concentrations but wide interpatient and intrapatient variations made individual predictions unreliable. Conclusions: The liquid-chromatography tandem-mass-spectrometry methods developed provided information useful to understand individual responses to therapy even though necessary sampling and dosing information was often not available. Wide unpredictable variations in t-IM, t-NDI, and f-IM were found. Clinical outcome trials are needed to examine whether f-IM or NDI monitoring can improve the ability to predict individual responses."],["dc.description.sponsorship","Novartis Pharma GmbH, Nuernberg, Germany"],["dc.identifier.doi","10.1097/FTD.0b013e3182263ac4"],["dc.identifier.isi","000295083000009"],["dc.identifier.pmid","21912334"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21930"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0163-4356"],["dc.title","Use of Total and Unbound Imatinib and Metabolite LC-MS/MS Assay to Understand Individual Responses in CML and GIST Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","988"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","European Journal of Gastroenterology & Hepatology"],["dc.bibliographiccitation.lastpage","994"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Armbrust, Thomas"],["dc.contributor.author","Sobotta, Michael"],["dc.contributor.author","Fuzesi, Laszlo"],["dc.contributor.author","Grabbe, Eckhardt"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T10:56:09Z"],["dc.date.available","2018-11-07T10:56:09Z"],["dc.date.issued","2007"],["dc.description.abstract","Background Although modern chemotherapy of stage IV advanced colorectal cancer (CRC) has impressively improved overall survival, the response of the primary tumor has not been studied because surgical resection of the primary continues to be the standard procedure in stage IV CRC. Aim Long-term follow-up of the primary in patients with stage IV CRC under chemotherapy. Methods and results Here we report on the histological changes in the primary tumor in four patients suffering from stage IV CRC. Systemic chemotherapy was started immediately after endoscopic tumor debulking in three cases. In one case no endoscopic intervention was performed before chemotherapy. Neither macroscopic nor histological evidence for malignant tumor growth was found at the former site of the primary after 6, 23, 26 or 48 months, respectively. Two patients had a complete suppression of the primary, two patients had an adenoma at the former site of the primary. To date, three patients have died because of progression of liver metastases and one patient is still alive with no signs of tumor growth. Conclusion The four cases illustrate that today's chemotherapy may effectively induces suppression of the primary in CRC. The development of CRC may follow different pathways."],["dc.identifier.isi","000254356700013"],["dc.identifier.pmid","18049169"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49947"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0954-691X"],["dc.title","Chemotherapy-induced suppression to adenoma or complete suppression of the primary in patients with stage IV colorectal cancer: report of four cases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]