[The non-hormonal treatment of metastatic prostate cancer]. / Le traitement non hormonal de la maladie métastatique du cancer de la prostate.

AIM: To describe drugs used in the non-hormonal treatment of metastatic prostate cancer. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: The metabolic radiotherapy although under-used for this indication, kept a place at the beginning of the disease. Radium-223 chloride seems to have to occupy an important place in the coming years. The chemotherapy, the only recourse until very recently in the castration-resistant prostate cancer, must redefine its place partially. The denosumab provide an interesting alternative to bisphosphonates. CONCLUSION: The non-hormonal treatment of the metastatic disease of the prostate cancer is changing rapidly with the emergence of new molecules. Urologist must know perfectly these new drugs.

[Cost-effectiveness of samarium-153-EDTMP for the treatment of pain due to multiple bone metastases in hormone-refractory prostate cancer versus conventional pain therapy, in Portugal]. / Análise custo-efectividade do samário-153-EDTMP versus terapêutica convencional da dor em doentes com metástases ósseas múltiplas dolorosas em Portugal.

INTRODUCTION: Prostate cancer is a significant cause of morbidity and mortality. In Portugal alone, according to a study published in 2003, the rate of new prostate cancer cases were 53 per 100,000 men (in 2000), with an age-standardized mortality rate of about 28 per 100,000 (in 1995). Multiple bone metastases are one of the major complications of advanced prostate cancer. Samarium-EDTMP showed to be a safe and effective alternative for palliative treatment of bone metastases. The goal of this economic study is to assess the cost-effectiveness of Samarium-153-EDTMP for the treatment of pain due to multiple bone metastases in hormone-refractory prostate cancer versus conventional pain therapy, in Portugal. METHODOLOGY: Cost-effectiveness study that compares the expected direct costs to the National Health System of managing patients with painful multiple bone metastases with Samarium-153-EDTMP versus conventional pain therapy, in Portugal, in a 4-moths period. RESULTS: The total direct 4 months cost was 2,311.91 euro for a patient treated with Samarium-153-EDTMP versus 2,450.74 euro for a patient under standard treatment. According to the model a patient treated with Samarium-153-EDTMP represents a 138.83 euros saving. CONCLUSION: Samarium-153-EDTMP was not only a very effective therapeutic option but also an option with less cost than the conventional pain therapy, in patients with pain due to multiple bone metastases, in Portugal.

[Cost-effectiveness analysis of samario-153 (Quadramet) for the treatment of patients with prostate cancer and bone metastases]. / Análisis coste-efectividad de samario-153 (Quadramet) en el tratamiento del dolor en pacientes con cáncer de próstata y metástasis óseas.

OBJECTIVE: To evaluate the cost-effectiveness of samarium [153Sm-EDTMP] (Quadramet) compared to conventional therapy in the treatment of pain in patients with prostate cancer and bone metastases. METHOD: A decision tree model for the treatment of bone pain due to metastases was adapted to the Spanish context. The model represents the standard treatment patterns in Spain for the study population. The time-course of the model is 4 months and it computes an estimate for the cost of pain control per patient. The effectiveness data for the model derive from a randomised trial. The current treatment patterns have been established according to the consensus opinions of a group of medical experts. RESULTS: The cost of pain control per patient is euro 12,515.39 for conventional therapy and euro 5,595.52 for samarium-153 (Quadramet) therapy. The incremental cost-effectiveness analysis shows that samarium-153 (Quadramet) is a dominant therapy. It presents lower costs and higher efficacy than the conventional strategy. The sensitivity analyses showed these results to be robust. CONCLUSION: Samarium-153 (Quadramet) is cost-effective in treating pain in patients with prostate cancer and bone metastases.

Análisis coste-efectividad de samario-153 (Quadramet®) en el tratamiento del dolor en pacientes con cáncer de próstata y metástasis óseas / Cost-effectiveness analysis of samario-153 (Quadramet®) for the treatment of patients with prostate cancer and bone metastases

Objetivo. Realizar un análisis coste-efectividad de samario [153Sm-EDTMP] (Quadramet®) respecto a la terapia convencional, para el tratamiento del dolor causado por metástasis óseas en pacientes con cáncer de próstata. Metodología. Se ha adaptado un modelo de árbol de decisión, que representa el tratamiento del dolor óseo metastásico, al contexto español. El modelo muestra las opciones terapéuticas habituales en el contexto sanitario español para la población del estudio. El horizonte temporal del modelo es de 4 meses y calcula el cociente coste-efectividad por paciente controlado. Los datos de eficacia del modelo provienen de un ensayo clínico aleatorizado. Las pautas de tratamiento habituales en España han sido indicadas por varios especialistas médicos. Resultados. El coste por paciente controlado para la terapia convencional es de 12.515,39 € y para la terapia con samario-153 (Quadramet®) es de 5.595,52 €. El análisis coste-efectividad incremental muestra que samario-153 (Quadramet®) es una terapia dominante, es decir, que presenta una mayor eficacia y un menor coste que la terapia convencional. Los resultados obtenidos han demostrado ser robustos en un extenso análisis de sensibilidad. Conclusiones. La terapia con samario-153 (Quadramet®) es eficiente en el tratamiento del dolor de pacientes con cáncer de próstata y metástasis óseas

Objective. To evaluate the cost-effectiveness of samarium [153Sm-EDTMP] (Quadramet®) compared to conventional therapy in the treatment of pain in patients with prostate cancer and bone metastases. Method. A decision tree model for the treatment of bone pain due to metastases was adapted to the Spanish context. The model represents the standard treatment patterns in Spain for the study population. The time-course of the model is 4 months and it computes an estimate for the cost of pain control per patient. The effectiveness data for the model derive from a randomised trial. The current treatment patterns have been established according to the consensus opinions of a group of medical experts. Results. The cost of pain control per patient is €12,515.39 for conventional therapy and € 5,595.52 for samarium-153 (Quadramet®) therapy. The incremental cost-effectiveness analysis shows that samarium-153 (Quadramet®) is a dominant therapy. It presents lower costs and higher efficacy than the conventional strategy. The sensitivity analyses showed these results to be robust. Conclusion. Samarium-153 (Quadramet®) is cost-effective in treating pain in patients with prostate cancer and bone metastases

Efficiency comparison between 99m Tc-tetrofosmin and 99m Tc-sestamibi myocardial perfusion studies.

The purpose of this investigation was to compare the efficiency of two different imaging protocols using two different clinically available 99mTc labelled myocardial perfusion tracers. One thousand one hundred and thirty-four imaging studies were performed prospectively, using either 99mTc-tetrofosmin or 99mTc-sestamibi, alternating the use of each tracer for a total period of 8 months. 99mTc-tetrofosmin rest studies were performed with injections of 259MBq-370MBq and imaging 30 min later. Exercise studies were performed with injections of 777MBq-1.11GBq and imaging 20 min later. 99mTc-sestamibi studies used doses similar to those in the 99mTc-tetrofosmin studies. Imaging followed a standard procedure, at 60 min after rest injection, and 30 min after exercise. For patients undergoing pharmacological stress testing99mTc-sestamibi was imaged 45 min after injection and 99mTc-tetrofosmin was imaged 30 min after injection. Variables analysed were (1) injection-to-imaging time for the procedure, and (2) the number of repeated scans because of extra cardiac activity. The completion time for the rest study was significantly shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (47.7+/-21.7 min vs 74.3+/-25.8 min P<0.0001). Likewise, the total study time was shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (90+/-32.7 min vs 124+/-37 min, P<0.0001). More importantly, the number of repeated scans was higher with 99mTc-sestamibi compared to 99mTc-tetrofosmin, 21.4% vs 10%, P=0.001 for rest studies and 16.4% vs 7.9% P=0.001 [corrected] for rest and stress. It was concluded that, using a same day rest/stress protocol, 99mTc-tetrofosmin provided higher patient throughput with fewer repeat scans. These factors may be considered for efficiency improvement in nuclear cardiology laboratories using 99mTc perfusion tracers.

Economic evaluation of systemic treatments for cytomegalovirus retinitis in patients with AIDS.

OBJECTIVE: To determine the cost of using systemic therapy to treat newly diagnosed cytomegalovirus (CMV) retinitis in persons with AIDS. DESIGN: Incidence-based simulation model of CMV treatment from a government payer perspective. SETTING: Swiss healthcare system. PATIENTS AND PARTICIPANTS: Patients with AIDS and newly diagnosed CMV retinitis. INTERVENTIONS: Patients were assigned to 1 of 4 treatment regimens for induction and maintenance therapy: (i) intravenous (IV) cidofovir induction and maintenance (cidofovir IV/IV); (ii) IV foscarnet induction and maintenance (foscarnet IV/IV); (iii) IV ganciclovir induction and maintenance (ganciclovir IV/IV); and (iv) IV ganciclovir induction and oral (PO) ganciclovir maintenance (ganciclovir IV/PO). Following a second relapse, patients were assigned to one of the other regimens. MAIN OUTCOME MEASURES: Time to first and subsequent progression, duration of maintenance treatment and direct medical expenditures [1998 Swiss francs (SwF)] . RESULTS: The median time to first progression was longest for cidofovir IV/IV, followed by foscarnet IV/IV, ganciclovir IV/IV and ganciclovir IV/PO. Mean survival was 13 months and mean costs for this period in the base case were lowest in those initially treated with cidofovir (SwF146,742), followed by initial treatment with foscarnet IV/IV (SwF194,809), ganciclovir IV/PO (SwF195,190) and ganciclovir IV/IV (SwF243,964). Costs were most sensitive to changes in efficacy estimates. CONCLUSIONS: Of the regimens studied, initiation of treatment with systemic cidofovir appears least costly over a 13-month period.

Cidofovir in the treatment of cytomegaloviral disease.

OBJECTIVE: To review the clinical pharmacology and microbiology of cidofovir in the therapy of cytomegalovirus (CMV) disease. DATA SOURCES: Pertinent literature was identified via a MEDLINE search (October 1986-February 1997), and data from abstracts presented at recent scientific meetings were also included; unpublished information was provided by the manufacturer. STUDY SELECTION: Antiviral activity data were included if widely accepted methodology was used. All clinical data currently available from human studies were also included. DATA SYNTHESIS: Cidofovir is similar to ganciclovir in mechanism of action; however, cidofovir does not require viral enzymes for activation. Although the half-life of cidofovir in plasma is only 2.6 hours, the intracellular half-life may be much longer, allowing efficacy with biweekly maintenance dosing. In vitro, cidofovir appears to be equally or more effective than the other agents currently available for the treatment of CMV. In vivo, cidofovir appears to be effective in delaying the progression of CMV retinitis, although no clinical trials to date have directly compared cidofovir with either ganciclovir or foscarnet. Current intravenous dose recommendations are 5 mg/kg once weekly for two doses (induction), and then 5 mg/kg once every other week (maintenance). Since cidofovir is cleared almost entirely by the kidneys, dosage adjustments must be made in patients with impaired renal function. Disadvantages of cidofovir primarily include its risks of adverse drug reactions, such as nephrotoxicity, which is likely to occur in up to 50% of patients if appropriate preventative measures are not taken. Neutropenia and constitutional reactions to probenecid are also commonly encountered during the course of cidofovir therapy. CONCLUSIONS: Cidofovir is the first acyclic phosphonate nucleoside antiviral agent to be approved for general use in the US. In addition to delaying the progression of CMV retinitis, cidofovir may provide some protective benefits to patients at risk for developing the disease and may be active against certain strains of virus resistant to other currently available therapies. Another advantage of cidofovir is its infrequent dosage schedule, which may prove beneficial in patients who are not compliant with daily intravenous dosing regimens. When determining the appropriate treatment for a patient with CMV retinitis, the benefits of using cidofovir must be weighed carefully against the risk of potentially serious adverse effects.

A pharmacoeconomic evaluation of cisplatin in combination with either etoposide or etoposide phosphate in small cell lung cancer.

To compare etoposide and etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) in maximizing the cost efficiency of care for patients with small cell lung cancer (SCLC), we obtained pharmacoeconomic data from a phase II randomized study of these agents. This clinical investigation assessed the efficacy and toxicity of etoposide phosphate combined with cisplatin in treating SCLC. In the economic analysis, we identified resources expended during chemotherapy and related concomitant procedures and matched them with the current procedure terminology level of costs for the provider and the payor. The valuation process was conducted in the specific point-of-care (outpatient v inpatient) setting. The appropriate pharmacoeconomic analytic tool used when comparators are considered to achieve equivalent clinical outcomes is cost-minimization analysis. We provide the cost-minimization analysis from two oncology care perspectives: the provider and the payor. In addition, a payor/ provider cost reduction model was constructed to illustrate the potential economic effects achieved through more efficient use of the outpatient chemotherapy facility due to the ease of administration of etoposide phosphate. The provider's average cost per patient for treating an SCLC patient for six cycles in US dollars is $26,764.48 for etoposide versus $26,026.70 for etoposide phosphate. The payor's average treatment cost per patient for treating an SCLC patient for six cycles for the respective regimens was $34,270.65 and $34,320.70. When the time savings associated with the etoposide phosphate regimen are applied to the outpatient chemotherapy facility, the adjusted average treatment costs per patient for the payor are $2,797.29 less than the costs for using the standard etoposide intravenous formulation. Delivering an etoposide phosphate regimen accrued adjusted savings of $2,897.03 per patient. Based on these results, etoposide phosphate is a superior pharmacoeconomic alternative compared with standard etoposide chemotherapy in managing SCLC. The potential increase in patient volume conferred by the relative simplicity of etoposide phosphate administration would have a significant impact on operations in terms of scheduling patients and staff and increasing operational efficiencies, thereby facilitating cost reductions in excess of $2,700 per patient when an etoposide phosphate regimen is chosen over an etoposide regimen.