Vinflunine in the treatment of bladder cancer

Vinflunine (VFL) is a third-generation bifluorinated semi-synthetic vinca alkaloid obtained by superacidic chemistry from its parent compound, vinorelbine. As with the other vinca alkaloids, the main antineoplastic effects of VFL arise from its interaction with tubulin, the major component of microtubules in mitotic spindles. In contrast to other vinca alkaloids, VFL shows some distinctive properties in terms of tubulin binding, possibly explaining its superior antitumor activity in vitro and in vivo compared with vinorelbine as well as its excellent safety profile. In transitional cell carcinoma (TCC), two single-agent phase II trials were performed testing VFL in platinum-pretreated patients, showing moderate response rates and promising disease control rates. Therefore, the first phase III trial in modern times for second-line TCC of the urothelium was designed in order to further investigate the activity of VFL. First results were presented at the 2008 ASCO conference. VFL appears to be a possible treatment option for patients with TCC progressing after first-line platinum-containing chemotherapy

The Melanin-Concentrating Hormone (MCH) System Modulates Behaviors Associated with Psychiatric Disorders

Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders

Second-line therapy in bladder cancer

PURPOSE OF REVIEW: To review new developments in second-line treatment for transitional cell carcinoma of the urinary bladder focusing on advances and findings within the last year. RECENT FINDINGS: So far no standard therapy has been established for pretreated patients with transitional cell carcinoma. Prognostic and predictive factors for response and outcome in pretreated patients have been studied retrospectively and will help to identify those who might benefit from intensive therapy and those who would rather improve their quality of life with best supportive care. Single-agent chemotherapy in this setting provided low response rates, short progression-free and overall survival. Vinflunine, a novel vinca-alkaloid, and best supportive care had a modest, but still significant benefit at a very moderate toxicity rate in a randomized phase III trial. As for second-line combination chemotherapy, response rates as well as potential toxicities are higher and the progression-free survival and overall survival benefits are still poorly understood. New chemotherapeutics and approaches like metronomic chemotherapy and novel agents are under investigation. SUMMARY: With vinflunine there is reasonable hope for a new standard chemotherapy in second-line management of transitional cell carcinoma. However, due to the reported results with single agents and combination chemotherapy, treatment within clinical trials is still the best choice in patients progressing after first-line chemotherapy

Rolle der Chemotherapie beim kastrationsresistenten Prostatakarzinom

Chemotherapieoptionen in der Behandlung des metastasierten kastrationsresistenten Prostatakarzinoms (CRPC) waren bis vor kurzem sehr limitiert. Mitoxantron war in den 1990er Jahren aufgrund seiner palliativen Wirksamkeit zugelassen worden. Erst mit der Einführung von Docetaxel brachen neue Zeiten in der Therapie des CRPC an. Prednison und Docetaxel alle 3 Wochen zeigten einen Overall-survival- (OS-)Benefit gemeinsam mit einer Verbesserung der Lebensqualität und einer Schmerzreduktion. Weitere chemotherapeutische Therapiestrategien sind eine Reinduktion mit Docetaxel nach Ansprechen auf die Erstlinientherapie. Cabazitaxel, ein neu entwickelter semisynthetisch hergestellter Mikrotubulusinhibitor, wurde vor kurzem für die Behandlung des CRPC nach Docetaxel zugelassen. Dieser Überblicksartikel soll durch die Chemotherapieoptionen führen und eine Hilfestellung für die Optimierung der Chemotherapien im klinischen Alltag geben. Chemotherapy options for the treatment of metastatic castration-resistant prostate cancer (CRPC) have been very limited for many decades. Until 2004, only mitoxantrone was approved, providing palliation, but no survival benefit. With the introduction of docetaxel, the landscape of chemotherapy for CRPC changed substantially. Prednisone and three-weekly docetaxel showed an overall survival (OS) benefit compared to mitoxantrone plus prednisone, in addition to a significant improvement of quality of life and pain reduction. Further strategies to treat CRPC with chemotherapy include reinduction with docetaxel in responding patients and the use of cabazitaxel, a novel semi-synthetic microtubule inhibitor, in the docetaxel-refractory population. This review article is meant to guide physicians through the optimal use of chemotherapy in CRPC patients in daily clinical practice

DFP-Literaturstudium - Therapie von Malignomen

Mit Änderungen bei der onkologischen Therapie des Harnblasenkarzinoms, des Nierenzellkarzinoms sowie des Prostatakarzinoms befasst sich der zweite Teil der Serie. Bei der Therapie des kastrations-resistenten Prostatakarzinoms beispielsweise kann man von einer neuen Ära der Behandlung sprechen

ACOs And Antitrust Enforcement: Familiar Rules Raise New Concerns

In particular, market-share based safety zones and mandatory review requirements place a premium on sound up-front antitrust analysis. Jane Willis, Mark Popofsky, & Daniel Bachner (Ropes & Gray)