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Taal W.,Daniel den Hoed University Hospital Rotterdam | Segers-Van Rijn J.M.W.,Daniel den Hoed University Hospital Rotterdam | Segers-Van Rijn J.M.W.,Haga Hospital | Kros J.M.,Erasmus University Rotterdam | And 5 more authors.
Journal of Neuro-Oncology | Year: 2012

Alternative temozolomide regimens have been proposed to overcome O 6-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100-150 mg/m 2/d (days 1-7 and 15-21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1-12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1-5 every 4 weeks schedule. © 2012 The Author(s).


Ayez N.,Daniel den Hoed University Hospital Rotterdam | De Ridder J.,Radboud University Nijmegen | Wiering B.,Radboud University Nijmegen | Oyen W.J.,Radboud University Nijmegen | And 2 more authors.
Digestive Surgery | Year: 2014

Background: The aim of this study was to determine whether selection with fluorine-18-deoxyglucose positron emission tomography (FDG-PET) imaging would result in an improved outcome in surgically treated patients with curative resection of colorectal liver metastases (CRLM), stratified by the clinical risk score (CRS) of Fong et al. [Ann Surg 1999;230:309-318]. Patients and Methods: Between January 2000 and December 2009, all patients who underwent resection for CRLM from two different university teaching hospitals in the Netherlands were analysed. Patients were stratified by the CRS. Results: In total 613 patients were eligible for analysis. There was no statistical difference in median disease-free survival (DFS) between patients with and without an FDG-PET scan in both low CRS [17 months (95% CI 12-22) vs. 14 months (95% CI 11-17), p = 0.332] and high CRS [14 months (95% CI 7-21) vs. 9 months (95% CI 8-10), p = 0.073]. There was no statistical difference in median overall survival (OS) between patients with and without an FDG-PET scan in both low CRS [64 months (95% CI 54-74) vs. 54 months (95% CI 42-66), p = 0.663] and high CRS [39 months (95% CI 23-55) vs. 41 months (95% CI 34-48), p = 0.903]. Conclusion: The present study could not demonstrate that patients selected by an FDG-PET scan before liver resection, and stratified by CRS, have an improvement in DFS or OS. © 2014 S. Karger AG, Basel.


Van Der Bol J.M.,Daniel den Hoed University Hospital Rotterdam | Visser T.J.,Erasmus University Rotterdam | Loos W.J.,Daniel den Hoed University Hospital Rotterdam | De Jong F.A.,Daniel den Hoed University Hospital Rotterdam | And 7 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole. Methods: A patient treated for colorectal cancer with single agent irinotecan received methimazole co-medication for Graves' disease. Irinotecan pharmacokinetics and side effects were followed during a total of four courses (two courses with and two courses without methimazole). Results: Plasma concentrations of the active irinotecan metabolite SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean increase of 14 and 67%, respectively) with methimazole co-medication, compared to irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate increased with 47% during concurrent treatment. Other possible confounding factors did not change over time. Specific adverse events due to methimazole co-treatment were not seen. Conclusions: Additional in vitro experiments suggest that these results can be explained by induction of UGT1A1 by methimazole, leading to higher SN-38G concentrations. The prescribed combination of these drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise physicians to be very careful in combining methimazole with regular irinotecan doses, especially in patients who are prone to irinotecan toxicity. © 2010 The Author(s).


PubMed | Daniel den Hoed University Hospital Rotterdam
Type: Journal Article | Journal: Journal of neuro-oncology | Year: 2012

Alternative temozolomide regimens have been proposed to overcome O(6)-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100-150 mg/m(2)/d (days 1-7 and 15-21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1-12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1-5 every 4 weeks schedule.


PubMed | Daniel den Hoed University Hospital Rotterdam
Type: Journal Article | Journal: Hematology (Amsterdam, Netherlands) | Year: 2016

Our increasing knowledge on the pathogenetic mechanisms involved in the growth of cancer cells and on the molecular basis of cancer has influenced the development of anticancer agents. The realization that new targets should be evaluated for anti-cancer drug treatment has a.o. led to the introduction of the taxoids and topoisomerase I inhibitors. Attacking the known targets in a more sophisticated way led to the development of drugs with increased target specificity like Tomudex and Gemcitabine. Finally, using old drugs more efficiently by using pharmacokinetic and pharmacodynamic ananlysis hold a promise for the near future.


PubMed | Daniel den Hoed University Hospital Rotterdam
Type: Case Reports | Journal: Cancer chemotherapy and pharmacology | Year: 2011

To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole.A patient treated for colorectal cancer with single agent irinotecan received methimazole co-medication for Graves disease. Irinotecan pharmacokinetics and side effects were followed during a total of four courses (two courses with and two courses without methimazole).Plasma concentrations of the active irinotecan metabolite SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean increase of 14 and 67%, respectively) with methimazole co-medication, compared to irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate increased with 47% during concurrent treatment. Other possible confounding factors did not change over time. Specific adverse events due to methimazole co-treatment were not seen.Additional in vitro experiments suggest that these results can be explained by induction of UGT1A1 by methimazole, leading to higher SN-38G concentrations. The prescribed combination of these drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise physicians to be very careful in combining methimazole with regular irinotecan doses, especially in patients who are prone to irinotecan toxicity.


PubMed | Daniel den Hoed University Hospital Rotterdam
Type: Journal Article | Journal: European journal of neurology | Year: 2013

An intensive weekly regimen of cisplatin was administered to 66 patients with solid cancer in doses varying from 70 to 85 mg/m(2) . The occurrence of sensory neuropathy was prospectively examined by assessment of neuropathic signs and symptoms and measurement of vibration perception threshold (VPT). Evaluation was performed before initiation of therapy and during follow-up until 3-12 months after the last cycle of cisplatin. A mild or moderate neuropathy developed in 47% of patients at 2 weeks after treatment This neuropathy continued to deteriorate until approximately 3 months after cessation of chemotherapy leading to a mild or moderate neuropathy in 71% of patients and a severe neuropathy in 9% of patients. Thereafter we observed a gradual but incomplete recovery. The high incidence of neuropathy we found may be explained by the prolonged observation period compared with earlier reports. The only factor correlated with severity of neuropathy was the cumulative dose of cisplatin, while there was no association with either pre-treatment VPT, age, sex, tumor type or co-treatment with etoposide. The progressing course up to approximately 3 months after the end of treatment underscores the need for prolonged follow-up in future studies on cisplatin neuropathy.-

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