A T van Oosterom

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (368)1608.27 Total impact

  • Ejc Supplements - EJC SUPPL. 01/2009; 7(2):597-597.
  • Bju International - BJU INT. 01/2007; 92.
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    ABSTRACT: Halofuginone (tempostatin) is a synthetic derivative of a quinazolinone alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to study the pharmacokinetics (PKs) of halofuginone when administered once or twice daily orally to patients with advanced solid tumours. Patients were treated with escalating doses of halofuginone at doses ranging from 0.5 to 3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the first and second course and assayed using a validated high-performance liquid chromatographic assay with mass spectrometric detection. Twenty-four patients received a total of 106 courses. The 'acute' MTD was reached at 3.5 mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for chronic administration was defined as 0.5mg/day with the requirement of 5HT3 antagonists to control nausea and vomiting considered as DLT. Several patients experienced bleeding complications on treatment with halofuginone in which a causal relationship could not be excluded. The PKs of halofuginone were linear over the dose range studied with a large interpatient variability. In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The recommended dose for phase II studies of halofuginone is 0.5mg administered orally, once daily.
    European Journal of Cancer 09/2006; 42(12):1768-74. · 5.06 Impact Factor
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    ABSTRACT: Oral administration of irinotecan (CPT-11) should allow sustained exposure to the drug without the inconvenience of intravenous delivery and with fewer side-effects. The present phase I trial of CPT-11, administered orally as a powder-filled capsule for 5 consecutive days every 3 weeks at doses ranging from 30 to 90 mg/m(2)/day, was conducted in 47 patients for whom a satisfactory standard treatment option was no longer available (24 males/23 females; median age 51 years, range 26-85). Tumour types included melanoma (11), colorectal (4), urinary tract (3), lung/pleura (4), thyroid (3), liver (3), gallbladder (2), cervix/uterus (3), breast (2), pancreas (2), carcinoma and other cancer types (10). A total of 171 cycles were administered (median 3, range 1-11). Dose limiting toxicities (DLTs) occurred during the first cycle in five of 31 patients in the dose-escalation part of the study: one patient at the 50 mg/m(2)/day dose level (diarrhoea grade 4); one patient at the 80 mg/m(2)/day dose level (prolonged neutropenia grade 4 and diarrhoea grade 3); and three patients at the 90 mg/m(2)/day dose level (diarrhoea, vomiting and neutropenia). The 80 mg/m(2)/day dose level was expanded, as a feasibility study, to include 16 additional patients, five of whom had received extensive prior pelvic irradiation. A further three patients in this cohort experienced DLTs, two of whom had received extensive prior pelvic irradiation. One patient died on study day 15 during the first cycle of oral CPT-11 following grade 3 diarrhoea, febrile neutropenia and a necrotic enterocolitis. Overall the grade 3/4 toxicities in 47 patients were asthenia (19%), anorexia (17%), neutropenia (14.9 %), diarrhoea (13%), nausea (12.7%), vomiting (8.5%) and thrombocytopenia (8.5%). Partial responses were observed in two melanoma patients and disease stabilisation was noted in 17 (36.1%) patients. Pharmacokinetic parameters were recorded for 46 patients. At the maximum tolerated dose, defined as 80 mg/m(2)/day for 5 days every 3 weeks, oral CPT-11 was shown to be well tolerated and safe with few of the haematological toxicities associated with the intravenous formulation.
    Annals of Oncology 08/2006; 17(7):1158-65. · 7.38 Impact Factor
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    ABSTRACT: Purpose. To evaluate the activity and safety of ecteinascidin (ET-743) in pretreated patients with advanced or metastatic soft tissue and bone sarcoma. Patients or subjects. Eighty-nine patients received ET-743 as a 24-hour continuous infusion at a dose of 900-1500 mug/m(2) every 3 weeks. Results. We observed one complete remission, 5 partial remissions, one minimal response, and 16 patients with a disease stabilization of 6 months or more. The objective response rate was 6.7% and the clinical benefit rate at 3 and 6 months was 37.7% and 23.4%, respectively. Responses were noted in patients with lipo-, leiomyo-, osteo-, and myogenic sarcoma, with a median duration of 9.85 months. Toxicity mainly involved an asymptomatic elevation of transaminases and neutropenia. Estimated 1- and 2-year survival rates were 39.4% and 15.8%. Median overall survival was 8.25 months. Discussion. This retrospective analysis confirms that ET-743 induces objective responses and progression arrest in a clinically relevant proportion of patients.
    Sarcoma 02/2006; 2006:56282.
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    ABSTRACT: EORTC protocol 30924 is an international randomized trial reporting a 7.3 year update of a 2 weekly regimen of high-dose intensity chemotherapy with M-VAC plus granulocyte colony stimulating factor (HD-M-VAC) compared to classic M-VAC in advanced transitional cell carcinoma (TCC). Two hundred and sixty three untreated patients with bidimensionally measurable TCC were included. In an intention to treat analysis, there were 28 complete responses (CR) (21%) and 55 partial responses (PR) (41%), for an overall response rate (RR) of 64% on the HD-M-VAC arm. On M-VAC, there were 12 CR (9%) and 53 PR (41%), for an overall RR of 50% . The P-value for the difference in CR was 0.009; and for RR, was 0.06. After a median follow-up of 7.3 years, 24.6% are alive on the HD-M-VAC arm vs. 13.2% on the M-VAC arm. Median progression-free survival was better with HD-MVAC (9.5 months) vs. M-VAC (8.1 months). The mortality hazard ratio (HR) was 0.76. The 2-year survival rate for HD-M-VAC was 36.7% vs. 26.2% for M-VAC. At 5 years, the survival rate was 21.8% in the HD-M-VAC vs. 13.5%. Median survival was 15.1 months on HD-MVAC and 14.9 months on M-VAC. There was one death from toxicity in each arm; and more patients died to malignant disease in the M-VAC arm (76%) than in the HD-M-VAC arm (64.9%). With longer follow-up initial results have been confirmed, and shows that HD-M-VAC produces a borderline statistically significant relative reduction in the risk of progression and death compared to M-VAC.
    European Journal of Cancer 02/2006; 42(1):50-4. · 5.06 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2006; 4(12):171-171.
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    ABSTRACT: New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9-79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7-66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5-91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6-93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.
    British Journal of Cancer 12/2005; 93(11):1209-14. · 5.08 Impact Factor
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    ABSTRACT: The diagnosis of gastrointesinal stromal tumours (GISTs) is widely based on morphological features and KIT (CD117) immunoreactivity. Most patients with advanced GISTs show a major clinical response after treatment with imatinib mesylate. The histopathological features of GISTs in patients on prolonged imatinib treatment have, thus far, not been addressed in detail. In this report, we present three patients with metastatic GISTs, who received more than 1 year of therapy with imatinib, and whose tumours changed their morphological and immunohistochemical characteristics during continued treatment with the drug. All three primary GISTs from these patients were classical spindle-type tumours, showing diffuse, strong CD117, CD34, and focal alpha-smooth muscle actin expression. During treatment, two clinically progressive and one clinically stable GIST revealed a diffuse epithelioid, or pseudopapillary epithelioid growth pattern, characterized by rounded cells with eosinophilic cytoplasm and uniform round-to-ovoid nuclei. In addition, GIST specimens from patients on therapy showed complete loss of CD117 immunoreactivity. Remarkably, two of these tumours also became CD34 immunonegative and in one case the progression was accompanied by desmin expression. KIT mutational analysis revealed the presence of distinct exon 11 mutant isoforms in all cases examined, while the same genotype was sustained in the base line and on-therapy tumour specimens, proving the common origin of analysed specimens. GISTs subject to imatinib treatment can undergo striking (immuno)phenotypic changes, which are not necessarily corroborated by new genotypic modifications. Because these may mimic other tumour types, this feature creates a differential diagnostic challenge, of which the pathologist should be aware.
    Histopathology 08/2005; 47(1):41-7. · 2.86 Impact Factor
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    ABSTRACT: The development of an on-column focusing gradient capillary LC method coupled to tandem mass spectrometry (quadrupole-linear ion trap) for the quantitative determination of the anticancer agent ZD1839 (Gefitinib, Iressa) in blood plasma is described. Plasma samples (0.2 ml) were extracted with methyl tert-butyl ether. The analytes of interest, ZD1839 and the internal standard [(2)H8]ZD1839 (ZD1839-d8) were eluted on a 50 mm x 1 mm, 5 microm particle size, capillary ODS Hypersil column using an aqueous ammonium acetate gradient at 40 microl/min. Mass spectrometric detection was performed by a Q-Trap tandem mass spectrometer with electrospray positive ionisation, and monitored in the multiple reaction monitoring transitions 447 >128 and 455 >136, respectively. The limit of quantification of ZD18395 was 0.1 ng/ml. The method proved to be robust, allowing quantification of ZD1839 with sufficient precision, accuracy and sensitivity.
    Journal of Chromatography 07/2005; 1082(1):2-5. · 4.61 Impact Factor
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    ABSTRACT: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.
    Annals of Oncology 05/2005; 16(4):566-78. · 7.38 Impact Factor
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    ABSTRACT: To assess the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary antitumor activity of oral irinotecan given in combination with capecitabine to patients with advanced, refractory solid tumors. Patients were treated from day 1 with irinotecan capsules given once daily for 5 consecutive days (50 to 60 mg/m2/d) concomitantly with capecitabine given twice daily for 14 consecutive days (800 to 1,000 mg/m2); cycles were repeated every 21 days. Twenty-eight patients were enrolled and received 155 cycles of therapy (median, five cycles; range, one to 18 cycles). With irinotecan 60 mg/m2/d and capecitabine 2 x 800 mg/m2/d, grade 3 delayed diarrhea in combination with grade 2 nausea (despite maximal antiemetic support) and grade 3 anorexia and colitis, were the first-cycle dose-limiting toxicities in two of six patients, respectively. At the recommended doses (irinotecan 50 mg/m2/d; capecitabine 2 x 1,000 mg/m2/d), side effects were mostly mild to moderate and uniformly reversible. Pharmacokinetic analysis showed that there was no interaction between oral irinotecan and capecitabine, and that body-surface area was not significantly contributing to the observed pharmacokinetic variability. Confirmed partial responses were observed in two patients with gallbladder carcinoma and in one patient with melanoma. Disease stabilization was noted in 16 patients. The recommended phase II doses for oral irinotecan and capecitabine are 50 mg/m2/d for 5 consecutive days, and 2 x 1,000 mg/m2/d for 14 consecutive days repeated every 3 weeks, respectively.
    Journal of Clinical Oncology 03/2005; 23(4):889-98. · 18.04 Impact Factor
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    ABSTRACT: This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m(2) as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma. Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal. One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months. ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.
    Journal of Clinical Oncology 02/2005; 23(3):576-84. · 18.04 Impact Factor
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    Neurochirurgie. 01/2005; 51(1):50-50.
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    ABSTRACT: Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal through gain of function mutations of the oncogene KIT. Imatinib offers the first effective treatment for patients with GISTs, but the therapeutic outcome strongly depends on the type of KIT mutation. We used ProteinChip technology to investigate whether GISTs with different KIT mutations express different proteins. In total, 154 proteins were significantly differentially expressed in GISTs with exon 9 KIT mutation compared to GISTs with exon 11 KIT mutation.
    Amino Acids 01/2005; 27(3-4):335-7. · 3.91 Impact Factor
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    ABSTRACT: To investigate the antitumor activity and the safety of RFS2000, an oral topoisomerase I inhibitor, in patients with advanced or metastatic urothelial tract tumors refractory to one prior chemotherapy regimen. Eligible patients were to have failed first line treatment for advanced or metastatic disease. Patients received RFS2000 as one daily oral intake at the dose of 1.5 mg/m(2)/day according to a "5 days on/2 days" off schedule continuously. One cycle was arbitrarily defined as a 3 week period. Sufficient oral fluid intake to prevent cystitis previously described in phase I trials with RFS2000 was recommended. Gehan design was used for sample size determination. Anti-tumor activity was evaluated according to the RECIST criteria and toxicity according to CTC version 2. Twenty patients received a total of 57 cycles (range 1-8). Grade 3-4 toxicity was observed in 10 patients requiring dose or schedule modifications. Hematological grade 3-4 toxicity was observed in 16% of the cycles. Only one patient experienced a partial response. RFS2000 could be administered orally as a "5 days on/2 days off" schedule continuously with a median dose intensity of 90.6% with an acceptable toxicity profile. However, RFS2000 did not exert significant activity in patients with advanced/metastatic urothelial tract tumors failing prior chemotherapy. The results of this study do not suggest further investigation of RFS2000 at the present dose and schedule for the treatment of urothelial tract tumors in this refractory population.
    Investigational New Drugs 09/2004; 22(3):329-33. · 3.50 Impact Factor
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    ABSTRACT: In MAG-camptothecin (MAG-CPT), the topoisomerase inhibitor camptothecin is linked to a water-soluble polymer. Preclinical experiments showed enhanced antitumour efficacy and limited toxicity compared to camptothecin alone. Prior phase I trials guided the regimen used in this study. The objectives were to determine the maximum tolerated dose, dose-limiting toxicities, safety profile, and pharmacokinetics of weekly MAG-CPT. Patients with solid tumours received MAG-CPT intravenously administered weekly for 3 weeks in 4-week cycles. At the starting dose level (80 mg x m(-2) week(-1)), no dose-limiting toxicities occurred during the first cycle (n=3). Subsequently, three patients were enrolled at the second dose level (120 mg x m(-2) week(-1)). Two of three patients at the 80 mg x m(-2) week(-1) cohort developed haemorrhagic cystitis (grade 1/3 dysuria and grade 2/3 haematuria) during the second and third cycles. Next, the 80 mg x m(-2) week(-1) cohort was enlarged to a total of six patients. One other patient at this dose level experienced grade 1 haematuria. At 120 mg x m(-2) week(-1), grade 1 bladder toxicity occurred in two of three patients. Dose escalation was stopped at 120 mg x m(-2) week(-1). Cumulative bladder toxicity was dose-limiting toxicity at 80 mg x m(-2) week(-1). Pharmacokinetics revealed highly variable urinary camptothecin excretion, associated with bladder toxicity. Due to cumulative bladder toxicity, weekly MAG-CPT is not a suitable regimen for treatment of patients with solid tumours.
    British Journal of Cancer 07/2004; 90(12):2261-7. · 5.08 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the tolerability, pharmacokinetic interaction and antitumor activity of gefitinib ("Iressa", ZD1839), an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, combined with gemcitabine and cisplatin in chemotherapy-naïve patients with advanced solid tumors. This was an open-label feasibility trial evaluating two doses of gefitinib (250 and 500 mg/day) in combination with gemcitabine and cisplatin. Gefitinib was administered daily from day 2 onwards. Gemcitabine 1250 mg/m(2) was given on days 1 and 8 and cisplatin 80 mg/m(2) on day 1 for up to six 3-week cycles. Patients could then continue to receive gefitinib monotherapy. Eighteen patients were entered, nine at each gefitinib dose level. Two patients developed dose-limiting toxicity: one grade 3 convulsion (250 mg/day dose group) and one grade 3 rash (500 mg/day dose group). The most frequently occurring adverse events in the combination phase were vomiting (17 patients), asthenia (16), nausea (14), diarrhea (14) and skin rash (13). The most common grade 3/4 adverse events were vomiting (seven patients), asthenia (six), thrombocytopenia (six), diarrhea (five) and anorexia (five). Pharmacokinetic analyses showed no apparent pharmacokinetic interaction between gefitinib and cisplatin or gemcitabine, with the exception of a possible small increase in the geometric mean exposure to gemcitabine seen on day 8 of therapy when given alone with the higher dose of gefitinib. Of 17 evaluable patients, nine had confirmed partial responses, seven had stable disease and one had progressive disease. Combination therapy of gefitinib with cisplatin and gemcitabine had a manageable and predictable safety profile, no major effect on exposure to any of the three drugs and antitumor activity.
    Annals of Oncology 06/2004; 15(5):831-8. · 7.38 Impact Factor
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    ABSTRACT: Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). In this study, GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer (EORTC) phase I/II clinical study of imatinib were examined for mutations of c-KIT/PDGFRA in order to explore whether the mutational status of the tumour predicts the clinical response to therapy. Mutations were screened by denaturing high-pressure liquid chromatography (DHPLC) and characterised by bi-directional DNA sequencing. Activating mutations of c-KIT or PDGFRA were found in 29 (78%) and 2 (6%) GISTs, respectively. Most c-KIT mutations involved exon 11 (n=24; 83%), all but one being an in-frame deletion; no isolated point mutations were found. The other c-KIT mutations included exon 9 AY 502-503 duplication (n=4; 14%) and exon 13 Lys-->Glu(642) missense mutation (n=1; 3%). Two tumours with no detectable c-KIT mutations demonstrated PDGFRA Asp-->Glu(842) amino acid substitutions. Patients with GISTs harbouring exon 11 mutations were more likely to achieve a partial response (PR) on imatinib therapy (83%) than all of the others (23%). The overall survival and progression-free survival rates for the entire group at 106 weeks were 78.3% and 46.9%, respectively. Based on a Kaplan-Meier analysis, patients with GISTs harbouring c-KIT mutations had longer median survival times and were less likely to progress than the other patients. These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy.
    European Journal of Cancer 04/2004; 40(5):689-95. · 5.06 Impact Factor
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    ABSTRACT: We evaluated the effect of different intervals and sequences of the vascular targeting agent combretastatin A-4 disodium phosphate (CA4DP) and CPT-11 administration on tumour growth delay and intratumoral uptake of CPT-11 using a syngeneic rhabdomyosarcoma tumour model. Irrespective of the administration sequence, the combination of CA4DP and CPT-11 significantly increases tumour growth delay in comparison with both drugs alone (P<0.001). Intratumoral CPT-11 concentration generally decreased (up to 5-fold) in the combination groups, while SN-38, the active metabolite of CPT-11, increased up to 9-fold. However, the increased amount of intratumoral SN-38 trapping after CA4DP injection did not correlate with the observed tumour growth delay. In conclusion, CA4DP significantly enhances the antitumour effect of CPT-11, which is not greatly influenced by the administration sequence, and which lacks a correlation with the intratumoral trapping of CPT-11 or SN-38. Mechanisms other than trapping are likely to be involved in the chemosensitising capacity of CA4DP.
    European Journal of Cancer 01/2004; 40(2):284-90. · 5.06 Impact Factor

Publication Stats

11k Citations
1,608.27 Total Impact Points


  • 1998–2006
    • Erasmus MC
      • Department of Internal Oncology
      Rotterdam, South Holland, Netherlands
    • University of Aberdeen
      • Institute of Medical Sciences
      Aberdeen, SCT, United Kingdom
  • 1997–2006
    • Universitair Ziekenhuis Leuven
      • Department of General medical oncology
      Leuven, VLG, Belgium
  • 1997–2005
    • Leuven University College
      Louvain, Flanders, Belgium
  • 1985–2005
    • Institut de Cancérologie Gustave Roussy
      Île-de-France, France
    • Rigshospitalet
      • Department of Oncology
      Copenhagen, Capital Region, Denmark
  • 2001–2004
    • University of Groningen
      • Department of Pulmonary Diseases
      Groningen, Province of Groningen, Netherlands
  • 2003
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 1997–2003
    • KU Leuven
      • • Department of Oncology
      • • Research unit for Experimental Psychology
      Leuven, VLG, Belgium
  • 2002
    • National Cancer Institute, Bratislava
      Presburg, Bratislavský, Slovakia
  • 1988–2002
    • Netherlands Cancer Institute
      • Department of Medical Oncology
      Amsterdamo, North Holland, Netherlands
  • 1979–2001
    • Leiden University Medical Centre
      • • Department of Gynaecology
      • • Department of Clinical Oncology
      Leiden, South Holland, Netherlands
  • 2000
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
    • Aarhus University Hospital
      • Department of Oncology
      Aarhus, Central Jutland, Denmark
  • 1988–2000
    • University of Antwerp
      • • Departement Chemie
      • • Departement Oncologie
      Antwerpen, Flanders, Belgium
  • 1999
    • Clinique Saint-Luc, Bouge
      Namen, Walloon Region, Belgium
    • European Organisation for Research and Treatment of Cancer
      Bruxelles, Brussels Capital Region, Belgium
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 1984–1997
    • Leiden University
      • Leiden Amsterdam Center for Drug Research
      Leyden, South Holland, Netherlands
  • 1989–1993
    • Universitair Ziekenhuis Antwerpen
      • Department of Radiology
      Antwerpen, Flanders, Belgium
  • 1988–1992
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1991
    • Hospital Central de Asturias
      Oviedo, Asturias, Spain
  • 1990–1991
    • VU University Amsterdam
      • Department of Medical Oncology
      Amsterdam, North Holland, Netherlands
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1986
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands