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P F A Mulders

Publications and source records attributed to P F A Mulders.

10 recordsLinked to original sources
PubMed2006

[The practice guideline 'Urinary-tract infections' (second revision) from the Dutch College of General Practitioners; a response from the perspective of urology].

The convenient and clearly organised structure of this second revision of the practice guideline on urinary-tract infections from the Dutch College of General Practitioners provides a clearly described role for the general practitioner in the diagnosis and treatment of such infections. Most striking is the change in the classification of diagnostic patient categories. It seems that pregnant women with urinary-tract infections represent an important group in extramural medicine. This revised guideline shows great promise for ensuring efficient and effective routing of the various patient groups presenting with urinary-tract infections at the office of the general practitioner.

Anti-Bacterial Agents↗
PubMed2006

A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma.

PURPOSE: WX-G250 is a chimeric monoclonal antibody that binds to carbonic anhydrase IX(G250/MN), which is present on greater than 95% of RCCs of the clear cell subtype. The suggested working mechanism of WX-G250 is by ADCC. Because the number of activated ADCC effector cells can be increased by a low dose interleukin-2 pulsing schedule, a multicenter study was initiated to investigate whether WX-G250 combined with LD-IL-2 could lead to an improved clinical outcome in patients with progressive RCC. MATERIALS AND METHODS: A total of 35 patients with progressive clear cell RCC received weekly infusions of WX-G250 for 11 weeks combined with a daily LD-IL-2 regimen. Patients were monitored longitudinally for ADCC capacity. Radiological assessment of metastatic lesions was performed at week 16 and regularly until disease progression. RESULTS: A durable clinical benefit was achieved in 8 of 35 patients (23%), including 3 with a partial response and 5 with stabilization at 24 weeks or greater. Mean survival was 22 months. In general treatment was well tolerated with little toxicity. The number of effector cells increased during treatment but lytic capacity per cell did not increase. ADCC and clinical outcome did not appear to correlate. CONCLUSIONS: WX-G250 combined with LD-IL-2 in patients with metastatic RCC is safe and well tolerated. With a substantial clinical benefit and a median survival of 22 months in patients with metastatic RCC who have progressive disease at study entry combination therapy showed increased overall survival compared to WX-G250 monotherapy. Survival was at least similar to that of currently used cytokine regimens but with a favorable toxicity profile.

Adult↗
PubMed2005

[The practice guideline 'Lower urinary-tract symptoms in middle-aged and elderly men' (second revision) from the Dutch College of General Practitioners; a response from the perspective of urology].

New insights in the fields of terminology, diagnosis and treatment have been successfully implemented in the second revision of the practice guideline 'Lower urinary-tract symptoms in middle-aged and elderly men' from the Dutch College of General Practitioners. The result is a coherent, lucid and moreover practical guideline. It is important to stress that lower urinary-tract symptoms do not increase the patient's risk of prostate cancer. Screening for prostate cancer by the routine measurement of serum prostate-specific antigen is therefore not indicated.

Aged↗
PubMed2005

Innovations in serum and urine markers in prostate cancer current European research in the P-Mark project.

An overview is given of serum and urine prostate cancer markers that are currently under investigation and subsequently the P-Mark project is introduced. There are many markers showing promise to overcome the limitations of prostate specific antigen (PSA). Eventually, these markers should be able to increase the specificity in diagnosis, differentiate between harmless and aggressive disease and identify progression towards androgen independence at an early stage. In the P-Mark project, several recently developed, promising markers will be evaluated using clinically well-defined biorepositories. Following successful evaluation, these markers will be validated on a sample set derived from two large, European, prostate cancer studies and used for the identification of special risk groups in the general population. In addition, novel markers will be identified in the same biorepositories by different mass spectrometry techniques.

Biomarkers, Tumor↗
PubMed2005

Novel treatments for metastatic renal cell carcinoma.

The mainstay of any curative treatment in renal cell carcinoma (RCC) is surgery. In case of metastatic disease at presentation a radical nephrectomy is recommended to good performance status patients prior to start of interferon-alfa treatment. Interferon-alpha (IFN-alpha) offers in a small but significant percentage of patients advantage in overall survival; interleukin-2 (IL-2) based therapy gives similar survival rates. To date hormonal and chemotherapy do not have a proven impact on survival. The recent new insights in the molecular biology of clear RCC has revealed a key-role for vascular endothelial growth factor (VEGF) in the stimulation of angiogenesis in this highly vascularized tumour. This opens interesting new treatment strategies including: blockage of VEGF with the monoclonal antibody bevacizumab and inhibition of VEGF receptor tyrosine kinases (with small oral molecules such as SU11248 or PTK787). Likewise, inhibition of the Raf kinase pathway (with oral Bay 43-9006) or inhibition of the mTOR pathway (with i.v. CCI-779) are under investigation. Preliminary clinical results with all these compounds are interesting and the results of ongoing phase III studies will become available in the next years.

Angiogenesis Inhibitors↗
PubMed2005

Novel treatment strategies in clear-cell metastatic renal cell carcinoma.

Metastatic renal-cell carcinoma (mRCC) is highly resistant to cytotoxic agents or hormones and is currently mainly treated with cytokine-based therapy. Transient responses and moderate survival advantages have been achieved in a subset of patients with these aspecific biological response modifiers. Side-effects are considerable, especially with high-dose interleukin (IL)-2. Efforts made in the field of specific immunotherapy have focused on optimization of dendritic cell vaccination and on administration of monoclonal antibodies, either cold (unconjugated) or hot (radioactively labeled). Furthermore, allogeneic bone marrow transplantation is able to induce remissions but, regrettably, is related to substantial morbidity and mortality. Neutralization of the biological activity of some immunosuppressive cytokines produced by RCC (IL-6 and tumor necrosis factor-alpha) with monoclonal antibodies is currently under investigation. Insights gained into the processes and pathways underlying carcinogenesis have led to the development of new treatment strategies. These treatments can be used for clear cell RCC, since they focus on blocking gene products that are upregulated by mutations in the von Hippel-Lindau gene. Specific strategies include anti-vascular endothelial growth factor monoclonal antibody (bevacizumab) or inhibition of its receptor kinases (oral SU11248 or PTK787), or targeting the Raf kinase pathway (by BAY 43-9006) or the mammalian target of rapamycin (mTOR) pathway (by CCI-779). Early clinical results are promising, but their place in the treatment of RCC has to be determined.

Adenocarcinoma, Clear Cell↗
PubMed2004

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients.

Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on >90% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.

Adult↗
PubMed2003

Erectile function after radical prostatectomy: a review.

OBJECTIVES: Although the high rate of erectile dysfunction (ED) following prostatectomy is well recognised, the aetiology and pathophysiology have not yet been fully elucidated. We examined the current literature as to aetiology, treatment and possible prevention of ED following prostatectomy. METHOD: Review of the literature by a Medline search. CONCLUSION: The most important predictors of erectile function are pre-operative erectile function and the nerve sparing nature of the procedure. The former is determined by age and vascular risk-factors whereas the latter is decided by the stage of the tumour and the skill of the surgeon. The value of intraoperative nerve mapping seems limited and the importance of nerve grafting is uncertain. Natural recovery of erection can take as long as 24 months. Patients complain about a lack of professional support. Symptomatic therapy may be applied according to the current general standards of treatment in men with ED.

Alprostadil↗