Biography:

In the past Antoine G. van der Heijden has collaborated on articles with Tom J.H. Arends and J. Alfred Witjes. One of their most recent publications is Adult urologyOncology: Adrenal/renal/upper tract/bladderPhase II Marker Lesion Study With Intravesical Instillation of Apaziquone for Superficial Bladder Cancer: Toxicity and Marker Response. Which was published in journal The Journal of Urology.

More information about Antoine G. van der Heijden research including statistics on their citations can be found on their Copernicus Academic profile page.

Antoine G. van der Heijden's Articles: (7)

Adult urologyOncology: Adrenal/renal/upper tract/bladderPhase II Marker Lesion Study With Intravesical Instillation of Apaziquone for Superficial Bladder Cancer: Toxicity and Marker Response

PurposeWe studied the ablative activity of intravesical apaziquone (EOquin™) on a papillary marker tumor and determined the incidence of side effects.Materials and MethodsA total of 46 patients with multiple pTa or pT1 bladder tumors underwent visible lesion resection except for 1 marker tumor. Patients were then treated with 6 instillations of apaziquone at weekly intervals. The response was determined 2 to 4 weeks after the last instillation.ResultsOne patient withdrew informed consent and refused the last treatment due to side effects. A histologically proven complete response was seen in 30 patients. Progression to invasive stage was not observed. Local side effects in this study were comparable to those due to other chemotherapy instillations, such as mitomycin C and epirubicin, but less severe and less frequent compared to those of bacillus Calmette-Guerin instillations.ConclusionsThe histological complete response rate after 6 consecutive instillations of apaziquone in patients with superficial bladder cancer was 67% (95% CI 51 to 80). Local side effects were comparable to side effects due to other chemotherapy instillations.

Adult UrologyOncology: Adrenal/Renal/Upper Tract/BladderCombined Chemohyperthermia: 10-Year Single Center Experience in 160 Patients with Nonmuscle Invasive Bladder Cancer

PurposeNonmuscle invasive bladder cancer is characterized by a high recurrence rate. New adjuvant treatments are needed to decrease this high number of recurrences. We present the results of more than 10 years of experience with chemohyperthermia in patients with nonmuscle invasive bladder cancer.Materials and MethodsUsing standardized medical record forms we prospectively collected patient and tumor characteristics of patients treated with chemohyperthermia between 2002 and 2013. Median followup was 75.6 months. Recurrence-free survival was the primary objective. The secondary objective was to observe recurrence-free survival differences in 1) the epirubicin group vs the mitomycin group and 2) the highly recurrent (greater than 2 recurrences in 24 months) nonmuscle invasive bladder cancer group vs the other groups.ResultsA total of 160 patients with nonmuscle invasive bladder cancer were included in study, including 20 (13%) treated with epirubicin and 129 (81%) previously treated with bacillus Calmette-Guérin. One and 2-year recurrence-free survival was 60% and 47%, respectively. Muscle invasive progression was seen in 4% of cases. Two-year recurrence-free survival in the epirubicin and mitomycin groups was 55% and 46%, respectively (p = 0.30). The highly recurrent nonmuscle invasive bladder cancer group had significant decreased recurrence-free survival compared to other groups (p <0.01). Patients treated with 2 or fewer vs greater than 2 transurethral bladder tumor resections before chemohyperthermia had higher recurrence-free survival (p = 0.01). On multivariable analysis the highly recurrent cancer criteria remained independently associated with decreased recurrence-free survival (HR 2.40, 95% CI 1.30–4.43, p = 0.01).ConclusionsChemohyperthermia is an effective approach to nonmuscle invasive bladder cancer for which standard intravesical treatments fail. Patients with highly recurrent disease before chemohyperthermia have lower recurrence-free survival. Furthermore, recurrence-free survival appears to improve with earlier chemohyperthermia. No significant differences were observed between the 2 chemotherapy agents.

GuidelinesEAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2013 Guidelines

AbstractContextThe European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments.ObjectiveTo provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence.Evidence acquisitionFor each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided.Evidence synthesisSmoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2–T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used.ConclusionsThis 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa.Patient summaryIn this paper we update the EAU guidelines on Muscle-invasive and Metastatic bladder cancer. We recommend that chemotherapy be administered before radical treatment and that bladder removal be the standard of care for disease confined to the bladder.

Platinum Priority – Bladder CancerEditorial by Jorg R. Oddens and Richard J. Sylvester on pp. 1053–1054 of this issueResults of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non–Muscle-invasive Bladder Cancer☆

AbstractBackgroundDespite adjuvant intravesical therapy, recurrences in non–muscle-invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data.ObjectiveTo compare CHT using mitomycin C (MMC) with bacillus Calmette-Guérin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC.Design, setting, and participantsBetween 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1-yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov (NCT00384891).Outcome measurements and statistical analysisThe primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients (n = 147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided.Results and limitationsThe 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group (p = 0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group (p = 0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias.ConclusionsCHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC.Patient summaryRecurrences in non–muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guérin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy.

Original studyRadical Cystectomy in a Dutch University Hospital: Long-Term Outcomes and Prognostic Factors in a Homogeneous Surgery-Only Series

AbstractBackgroundThe aim of this study was to present survival outcomes and identify prognostic factors in patients undergoing radical cystectomy (RC) for urothelial bladder cancer (UBC) in a homogeneous surgery-only series.Patients and MethodsPatients who underwent RC for UBC with intent-to-cure between January 1998 and December 2010 without neoadjuvant or adjuvant treatment were included in this retrospective study. Clinical and histopathologic data were collected and institutional review board approval was obtained. Outcomes of interest were 30-day mortality (30dM), RFS, and OS. Univariable and multivariable analysis were performed. Median follow-up was 9.1 years.ResultsTwo hundred forty-five patients were included with a median age of 65 years (range, 34-92 years). 30dM rate was in 5 out of 245 patients (2.0%) and 5-year RFS and OS rates were 67% and 58%, respectively. A total of 223 patients (91%) underwent lymph node (LN) dissection. Median number of removed and positive LNs were 9 and 1.5, respectively. Variables independently associated with decreased OS and RFS were tumor stage and LN status. In addition, positive soft tissue surgical margin (STSM) status was independently associated with decreased OS. In LN-positive patients, presence of extranodal extension (ENE) was associated with decreased RFS (39.7% vs. 7.3%; P = .005).ConclusionRadical cystectomy for UBC was associated with low perioperative mortality rate and provided 5-year disease control in approximately two-thirds of patients. Independent prognostic factors included tumor stage, LN status (RFS and OS), and STSM status (OS). Presence of ENE in LN-positive patients was univariably associated with decreased RFS and OS.

Original StudyPharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer

AbstractIntroduction/BackgroundNon-muscle-invasive bladder cancer (NMIBC) has a strong tendency to recur despite adjuvant instillations. TMX-101 is a new liquid form of imiquimod for intravesical instillation and has activity in vitro against urothelial carcinoma. The purpose was to analyze the activity of TMX-101 in low-grade NMIBC. Furthermore, pharmacokinetic and pharmacodynamic characteristics and adverse events were evaluated.Patients and MethodsA multicenter, prospective phase 1 trial in 7 patients with low-grade NMIBC was conducted. All patients underwent a marker lesion transurethral resection of the bladder tumor and 6 weekly instillations with TMX-101 0.2% or 0.4%. Cystoscopy 2 to 4 weeks after the last instillation evaluated the effect of TMX-101.ResultsThe effective biologic dose (EBD = complete response [CR] in > 2 patients) could not be defined because none of the patients experienced CR. Maximum plasma concentration was 75.1 ng/mL in the 0.4% dose group. No drug accumulation was observed. In the pharmacodynamic analysis, urinary interleukin 1 receptor agonist (IL-1ra) represents the most sensitive and uniform response after TMX-101 instillation. A total of 87.0% reported at least 1 adverse event. All events were of grade 2 severity or less (Common Terminology Criteria of Adverse Events version 4.02). No clinically significant changes in laboratory parameters or vital signs were observed during or after treatment.ConclusionToll-like receptor 7 (TLR-7) agonists are effective in urothelial carcinoma in preclinical research. The EBD in this phase 1 study could not be determined because no patient experienced CR. IL-1ra could be valuable as a urinary biomarker in future developments. The safety of TMX-101 has been reconfirmed. New doses, other schedules, and NMIBC subgroups should be tested to define the EBD. A pilot study in carcinoma-in-situ patients is currently ongoing and results are expected shortly.

Recurrence, Progression, and Follow-Up in Non–Muscle-Invasive Bladder Cancer

AbstractNon–muscle-invasive bladder cancer (NMIBC) is characterized by a high risk of recurrence after transurethral resection of an initial tumor; the 1-yr recurrence rate is 15–61%, and the 5-yr recurrence rate is 31–78%. These figures represent the heterogeneous character of NMIBC. The treatment and follow-up (FU) strategy vary depending on initial and subsequent clinical and histopathological characteristics. Clinical prognostic factors for recurrence and progression are size, multiplicity, reaction to intravesical therapy, grade, stage, and the presence of carcinoma in situ. In addition, recurrence anywhere in the bladder at first FU cystoscopy after transurethral resection is one of the most important prognostic factors for time to progression.The major goals in treating patients with NMIBC are to prevent the high number of recurrences and to prevent muscle-invasive progression. In this review, risks of recurrence and progression are analyzed and discussed in separate sections, including clinical and pathological results, applied treatments, and diagnostics. Finally, means and recommendations for FU are discussed.

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