W Wynendaele

Publications (12)60.24 Total impact

• Article: Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer.

  H Wildiers, P Neven, M R Christiaens, P Squifflet, F Amant, C Weltens, A Smeets, E van Limbergen, G Debrock, V Renard, L Van Eenoo, W Wynendaele, R Paridaens
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  ABSTRACT: To evaluate capecitabine-docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC). Patients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m(2) twice daily, days 1-14, plus docetaxel 36 mg/m(2), days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The primary end point was pathologic complete response (pCR) rate, evaluated separately in HER2-negative and HER2-positive cohorts. Secondary end points included clinical response rates and tolerability. The pCR rate was 15% [95% confidence interval (CI) 7-28] in 53 patients receiving XT and 40% (95% CI 26-55) in 50 patients receiving HXT. After neoadjuvant therapy, 50 patients receiving XT and 45 receiving HXT underwent surgery. No unexpected toxicity was observed: the most common grade ≥3 adverse events were diarrhea/mucositis (30% and 20%, respectively) and grade 3 hand-foot syndrome (11% and 6%, respectively). Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort. Neoadjuvant XT (HXT in HER2-positive disease) is highly effective in inoperable LABC, demonstrating pCR rates of 15% and 40%, respectively. This non-anthracycline-containing regimen offers obvious benefits in early disease, where avoidance of long-term cardiotoxicity is particularly important.
  Annals of Oncology 03/2011; 22(3):588-94. · 6.43 Impact Factor
• Source

  Available from: Vincent Launay-Vacher

  Article: Cancer and renal insufficiency results of the BIRMA study

  N Janus, V Launay-vacher, E Byloos, J-P Machiels, L Duck, J Kerger, W Wynendaele, J-L Canon, W Lybaert, J Nortier, G Deray, H Wildiers
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  ABSTRACT: Background: Half of anticancer drugs are predominantly excreted in urine. Dosage adjustment in renal insufficiency (RI) is, therefore, a crucial issue. Moreover, patients with abnormal renal function are at high risk for drug-induced nephrotoxicity. The Belgian Renal Insufficiency and Anticancer Medications (BIRMA) study investigated the prevalence of RI in cancer patients, and the profile/dosing of anticancer drugs prescribed.
  British Journal of Cancer 11/2010; 103(12):1815-1821. · 5.04 Impact Factor
• Source

  Available from: Vincent Launay-Vacher

  Article: Cancer and renal insufficiency results of the BIRMA study.

  N Janus, V Launay-Vacher, E Byloos, J-P Machiels, L Duck, J Kerger, W Wynendaele, J-L Canon, W Lybaert, J Nortier, G Deray, H Wildiers
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  ABSTRACT: half of anticancer drugs are predominantly excreted in urine. Dosage adjustment in renal insufficiency (RI) is, therefore, a crucial issue. Moreover, patients with abnormal renal function are at high risk for drug-induced nephrotoxicity. The Belgian Renal Insufficiency and Anticancer Medications (BIRMA) study investigated the prevalence of RI in cancer patients, and the profile/dosing of anticancer drugs prescribed. primary end point: to estimate the prevalence of abnormal glomerular filtration rate (GFR; estimated with the abbreviated Modification of Diet in Renal Disease formula) and RI in cancer patient. Secondary end point: to describe the profile of anticancer drugs prescribed (dose reduction/nephrotoxicity). Data were collected for patients presenting at one of the seven Belgian BIRMA centres in March 2006. a total of 1218 patients were included. The prevalence of elevated SCR (> or =1.2 mg per 100 ml) was 14.9%, but 64.0% had a GFR<90 ml min(-1) per 1.73 m(2). In all, 78.6% of treated patients (n=1087) were receiving at least one drug needing dosage adjustment and 78.1% received at least one nephrotoxic drug. In all, 56.5% of RI patients receiving chemotherapy requiring dose reduction in case of RI did not receive dose adjustment. the RI is highly frequent in cancer patients. In all, 80% of the patients receive potentially nephrotoxic drugs and/or for which dosage must be adjusted in RI. Oncologists should check the appropriate dose of chemotherapeutic drugs in relation to renal function before prescribing.
  British Journal of Cancer 11/2010; 103(12):1815-21. · 5.04 Impact Factor
• Source

  Available from: Jean-Luc Canon

  Article: Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer.

  H Wildiers, C Fontaine, P Vuylsteke, M Martens, J L Canon, W Wynendaele, C Focan, J De Greve, P Squifflet, R Paridaens
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  ABSTRACT: The aim of this study is to test the hypothesis that antiangiogenic treatment with sunitinib consolidation can prolong remissions induced by taxane-based chemotherapy in women with metastatic breast cancer. The method involves a two-arm open-label (2:1 randomization) multicenter, randomized phase II trial evaluating the efficacy of sunitinib (arm A) versus no therapy (arm B) in patients with HER-2-negative metastatic breast cancer who achieved an objective response to taxane-based chemotherapy. The results of this study indicates that the primary endpoint of progression-free survival (PFS) > or =5 months was achieved in 10 of 36 patients (28%) in arm A and 4 of 19 patients (21%) in arm B. The median PFS was 2.8 and 3.1 months, respectively. A protocol amendment to the sunitinib dosing schedule was made because 53% (17/32) of patients treated at a starting dose of 50 mg (4 weeks on/2 weeks off) required dose reduction. Changing the starting dose to sunitinib 37.5 mg continuously resulted in dose reductions in 44% (7/16) of patients. Grades III-IV toxicity occurred in 69% of patients in arm A (fatigue 31%, musculoskeletal pain 11%, neutropenia and thrombopenia 8%) and 11% in arm B. The proof-of-principle study does not confirm the hypothesis that sunitinib consolidation therapy can lead to a predefined clinically relevant proportion of patients with PFS of > or =5 months after an objective response to taxanes. Furthermore, toxicity was significant.
  Breast Cancer Research and Treatment 09/2010; 123(2):463-9. · 4.43 Impact Factor
• Article: Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions.

  M Saad Ismail, W Wynendaele, J L E Aerts, R Paridaens, L Van Mellaert, J Anné, R Gaafar, N Shakankiry, H M Khaled, M R Christiaens, S Omar, P Vandekerckhove, A T Van Oosterom
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  ABSTRACT: We previously developed a real-time quantitative RT-PCR technique to detect breast carcinoma cells in peripheral blood (PB). The aim of the current study was to improve cytokeratin 19 (CK19) quantification using plasmid dilutions of cloned PCR fragments to obtain a more reliable and reproducible quantification of CK19 transcripts. PB samples of 14 stage IV breast cancer patients and 23 healthy controls were examined with RT-PCR using plasmid quantification. Median CK19+ copy numbers of one and 11 were detected in the control group and stage IV breast cancer patients, respectively (Mann-Whitney, P </=0.0001). When comparing the results obtained using cell line dilutions with those obtained using plasmid dilutions, a good correlation was observed (r(2) = 0.98). Plasmid dilutions are more reliable than cell line dilutions for quantification of gene expression, and more objective criteria for positivity could be defined based on the characteristics of the standard curve (slope and intercept). A more universally accepted agreement on the definition of the cut-off value for positivity is needed.
  Annals of Oncology 08/2003; 14(8):1241-5. · 6.43 Impact Factor
• Article: Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours.

  F A L M Eskens, H Dumez, R Hoekstra, A Perschl, C Brindley, S Böttcher, W Wynendaele, J Drevs, J Verweij, A T van Oosterom
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  ABSTRACT: A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins alphavbeta3 and alphavbeta5, was performed to determine its safety and toxicity. Cilengitide was administered as a one-hour infusion twice weekly without interruption to patients with histologically- or cytologically-confirmed metastatic solid tumours. Plasma pharmacokinetics were determined at days 1 and 15. 37 patients were enrolled into the study. Dose levels studied were 30, 60, 120, 180, 240, 400, 600, 850, 1200, and 1600 mg/m(2)/infusion. There was no dose-limiting toxicity (DLT). Pharmacokinetics were dose-independent and time-invariant. Apparent terminal half-life ranged from 3 to 5 h. At 120 mg/m(2)/infusion, peak plasma concentrations were attained that optimally inhibited tumour growth in preclinical models. Cilengitide can be safely administered using a continuous twice-weekly infusion regimen. As DLT was not reached, future trials should explore Cilengitide at different doses.
  European Journal of Cancer 06/2003; 39(7):917-26. · 5.54 Impact Factor
• Article: PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors: a phase I and pharmacokinetic study.

  H J Groen, E G de Vries, W Wynendaele, W T van der Graaf, E Fokkema, M J Lechuga, I Poggesi, L Y Dirix, A T van Oosterom
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  ABSTRACT: Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor effect in murine solid tumors. In a Phase I study, PNU-145156E was administered i.v. every 6 weeks. Included were patients with solid tumors; an Eastern Cooperative Oncology Group performance score </=1; and normal bone marrow, renal, and liver functions and blood clotting tests. Excluded were patients with brain metastases or on steroid medication. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria. Plasma and urine PNU-145156E was measured for pharmacokinetic analysis. The effect of PNU-145156E on serum basic fibroblast growth factor (bFGF) was measured by sandwich ELISA. Twenty-nine patients (median age, 54 years; range, 33-71 years; 19 males and 10 females; median performance score = 1) were treated at dose levels of 100-1050 mg/m(2). We observed, during 47 treatment cycles, erratic but short-lasting decreases of antithrombin III levels (<75%) at all dose levels. Other clotting tests remained normal except during thromboembolic events. Dose-limiting toxicity was thrombophlebitis, pulmonary embolism, and grade 3 dyspnea. PNU-145156E disappeared from the circulation, decreasing triexponentially with a long terminal half-life of 1 month. No significant change in bFGF and no objective tumor responses were observed. Disease stabilization was achieved in four patients. In conclusion, the MTD of PNU-145156E was 1050 mg/m(2). Serum bFGF level was not affected by PNU-145156E up to the MTD.
  Clinical Cancer Research 12/2001; 7(12):3928-33. · 7.74 Impact Factor
• Source

  Available from: Joeri L Aerts

  Article: A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood.

  J Aerts, W Wynendaele, R Paridaens, M R Christiaens, W van den Bogaert, A T van Oosterom, F Vandekerckhove
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  ABSTRACT: The detection of occult carcinoma cells in patients with breast cancer has been shown to predict disease recurrence and metastasis. To improve on molecular detection of breast carcinoma cells in blood, we have developed a sensitive and quantitative assay using real-time quantitative RT-PCR identifying transcripts of the cytokeratin-19 (CK19) gene. This real-time quantitative RT-PCR is sensitive, accurate and has a high reproducibility within a wide dynamic range, which permits simultaneous quantitative analysis of samples with varying input concentrations. Furthermore, the procedure offers several technical advantages over classic quantitative PCR methods (competitive RT-PCR, Northern blotting) such as decreased likelihood of contamination due to absence of post-PCR manipulations, high sample throughput because of absence of post-PCR processing time (no agarose gel electrophoresis). In this pilot study, we detected significantly elevated CK19 transcript levels in < 10% of the volunteers, in +/- 30% of stage I-IIIa patients preoperatively and in > 70% of the and stage IV breast cancer patients. Analyses using this real time quantitative RT-PCR for CK19 mRNA may prove to have clinical implications in the assessment of circulating tumour cells in peripheral blood, micrometastases in bone marrow or lymph nodes in breast cancer patients. Application of this technique in a clinical population may improve diagnosis and monitoring of metastatic breast cancer and its validation is currently ongoing.
  Annals of Oncology 02/2001; 12(1):39-46. · 6.43 Impact Factor
• Article: Vascular targeting of solid tumours: a major 'inverse' volume-response relationship following combretastatin A-4 phosphate treatment of rat rhabdomyosarcomas.

  W Landuyt, O Verdoes, D O Darius, M Drijkoningen, S Nuyts, J Theys, L Stockx, W Wynendaele, J F Fowler, G Maleux, W Van den Bogaert, J Anné, A van Oosterom, P Lambin
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  ABSTRACT: Tumour-specific vascularisation may be therapeutically approached in two different ways: by antiangiogenic treatments specifically directed to dividing and migrating endothelial cells, or by agents that target principally the inadequate and ill-structured tumour vasculature. Combretastatin A-4 phosphate (combreAp), a recently synthesised prodrug (OXiGENE, Lund, Sweden), is a vascular targeting agent of the latter kind. We evaluated the effect of a single intraperitoneal (i.p.) combreAp injection on the growth of rhabdomyosarcomas syngeneic in WAG/Rij rats. Different tumour volume groups, ranging between 0.1 and 27 cm(3), were selected to assess the relationship between the size at treatment time and the response to combreAp. A double combreAp treatment (2x25 mg/kg) was investigated within the same overall aim: the relationship between growth delay and tumour size. Our results show that the systemic administration of combreAp induces a clear-cut differential growth delay in the solid rat rhabdomyosarcomas: with very large tumours (>/= 14 cm(3)), a 17.6-fold stronger effect was measured than with very small tumours (<1 cm(3)). This is the 'inverse' of the volume-response seen with the conventional therapeutic approaches (radiotherapy, chemotherapy or surgery). These combreAp antitumour responses were observed without treatment limiting systemic toxicity in the rats. With clinical digital subtraction angiography, using microsurgical cannulation of a major tumour draining vessel, and with histopathology, we demonstrate that growth delay is related to an early (within 3-6 h) and extensive breakdown of tumour blood vessels. The experiments involving a second injection also indicate a volume-dependent effect of combreAp in reducing the regrowth rate of small or large rhabdomyosarcomas. This significant differential volume-response obtained with 'selective' vascular targeting, stronger in larger tumours than smaller ones, suggests the potential of broadening the therapeutic window.
  European Journal of Cancer 10/2000; 36(14):1833-43. · 5.54 Impact Factor
• Source

  Available from: Marc F Hoylaerts

  Article: Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo?

  W Wynendaele, R Derua, M F Hoylaerts, A Pawinski, E Waelkens, E A de Bruijn, R Paridaens, W Merlevede, A T van Oosterom
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  ABSTRACT: Serum VEGF levels are elevated in cancer patients and are used as a tumor marker in different malignancies. We have measured VEGF levels in different blood compartments in cancer patients and healthy volunteers in order to assess the most suitable way of processing blood for measuring VEGF as a marker of tumor-angiogenesis. VEGF concentrations were analyzed by an enzyme-linked immunosorbent assay in serum (VEGFS), EDTA plasma (VEGFEDTA), citrated plasma (VEGFC), CTAD-plasma (VEGFCTAD), platelet poor plasma (VEGFPPP), platelet rich plasma after induction of platelet activation (VEGFPRP). Platelet activation was assessed by measuring PF4 concentrations in different plasma samples. We observed higher VEGFS (P = 0.0027), VEGFEDTA (P = 0.003) and VEGFPPP (P = 0.0007) levels in cancer patients than in volunteers; VEGFPRP concentrations showed no significant difference (P = 0.208). Analysis of the correlation between VEGFplt and VEGFS in cancer patients showed a similar correlation in a comparable VEGFS concentration range as in the volunteers. When comparing VEGFC to VEGFCTAD, we find significantly higher VEGF and PF4 levels in citrated plasma (VEGF: P = 0.00019; PF4: P = 0.00023). It is likely that VEGFS in cancer patients encompass platelet-delivered VEGF and VEGF from other sources, notably from (neo)-angiogenesis in tumoral tissue. The best discrimination between volunteers and cancer patients was observed in PPP. As generating plasma can induce platelet activation, with consequent VEGF release from platelets, we suggest that to assess free circulating VEGF, CTAD plasma should be used.
  Annals of Oncology 09/1999; 10(8):965-71. · 6.43 Impact Factor
• Article: Angiogenesis: possibilities for therapeutic interventions.

  W Wynendaele, A T van Oosterom, A Pawinski, E A de Bruijn, R A Maes
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  ABSTRACT: Vascular proliferation normally occurs only during embryonic development, the female reproductive cycle and wound healing. Various pathological conditions such as diabetic retinopathy are characterized by persistent, uncontrolled angiogenesis. At the other hand, impaired development of new blood vessels has been found to be related with myocardial infarction. A series of anti-angiogenic drugs are currently included in experimental cancer treatment, whereas the failure of ulcers to heal may be limited by increased angiogenesis upon administration of growth factors. In the present review control mechanisms of the vasculature are summarized and therapeutic approaches discussed.
  Pharmacy World amp Science 01/1999; 20(6):225-35. · 1.22 Impact Factor
• Article: Neoadjuvant/primary chemotherapy in cancer treatment: what advantage?

  W Wynendaele, A T van Oosterom
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  ABSTRACT: Neoadjuvant chemotherapy refers to the initial systemic treatment for patients who present with localised cancer for whom there is an alternative but less than completely effective local treatment. There are a multiple reasons for the use of neoadjuvant chemotherapy, but, there may be potential disadvantages. Several neoplasms in which neoadjuvant chemotherapy, if effective, can allow less mutilating surgery and neoplasms in which clinical trials indicate an expanding role for neo-adjuvant therapy are discussed.
  Forum (Genoa, Italy) 9(3):212-21.