Results of a Phase II Study of Pixantrone in Combination with Cyclophosphamide, Vincristine, and Prednisone in Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma.

Abstract Background: Pixantrone is a novel aza-anthracenedione with less cardiotoxicity and superior activity compared to doxorubicin and mitoxantrone in murine leukemia and lymphoma tumor models. Pixantrone as single agent therapy led to major responses in patients (pts) with multiply relapsed aggressive non-Hodgkin’s lymphoma (NHL), including diffuse large B-cell lymphoma (DLCL). In a phase I dose-ranging study of pixantrone (80 to 180 mg/m2) replacing doxorubicin (CPOP) in a CHOP-like regimen, the optimal dose (RD) from that study was found to be 150 mg/m2. Methods: In this international, multi-center, phase II study the primary objective was to assess the efficacy and safety of the CPOP…

Détection d’un disaccharide (MSDS) par spectrométrie de masse. Analyse multicentrique de son intérêt pour le diagnostic des infections fongiques invasives

Introduction Nous avons recemment decrit une methode utilisant la spectrometrie de masse MALDI-TOF pour detecter, identifier et quantifier un disaccharide (MSDS) dont la presence dans le serum est associee aux infections fongiques invasives (IFI). Nos premieres investigations, portant sur des cas de candidoses et d’aspergilloses invasives (IC et IA) recrutes dans notre CHU, ont montre que les performances diagnostiques de cette methode etaient comparables a celles des tests Platelia™ et Fungitell ® et qu’en outre elle permettait de diagnostiquer les mucormycoses (MM) pour lesquelles ces tests serologiques sont en defaut. Cette etude a comme objectif de confirmer ces resultats de maniere mul…

Forty-one recent cases of invasive zygomycosis from a global clinical registry.

Background Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response are limited. Patients and methods Fungiscope-A Global Rare Fungal Infection Registry is an international university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net. Results Forty-one patients with invasive zygomycosis from central Europe and Asia were registered. The most common underlying conditions were malignancies (n = 26; 63.4%), diabetes mellitus (n = 7; 17.1%) and solid organ transplantation (n = 4; 9.8%). Diagnosis was made by culture …

Forty-One Recent Cases of Invasive Zygomycosis From a Global Clinical Registry.

Abstract Abstract 4736 Background Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response is limited. Methods Fungiscope” - A Global Rare Fungal Infection Registry is a university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net. Results Fourty-one patients with invasive zygomycosis were registered. Five were pediatric (12.2%), 28 (68.3%) male. Median age was 49 years (range 2-88). Most common underlying conditions were malignancies (n=26; 63.4%), diabetes mellitus (n=7; 17%) and solid organ transplant (n=4; 9…

European expert opinion on the management of invasive candidiasis in adults

Item does not contain fulltext This report discusses the present status of antifungal therapy and treatment options for candidaemia, considered by experts in the field in Europe. A conference of 26 experts from 13 European countries was held to discuss strategies for the treatment and prevention of invasive candidiasis, with the aim of providing a review on optimal management strategies. Published and unpublished comparative trials on antifungal therapy were analysed and discussed. Commonly asked questions about the management of candidaemia were selected, and possible responses to these questions were discussed. Panellists were then asked to respond to each question by using a touchpad ans…

Reply to Denning

Treatment outcome of invasive mould disease after sequential exposure to azoles and liposomal amphotericin B

Objectives To analyse the potential antagonism between azoles, which inhibit ergosterol synthesis, and polyenes, which bind directly to ergosterol in cell membranes, in patients receiving sequential azole-polyene treatment. Methods In an earlier randomized, double blind study of liposomal amphotericin as initial therapy for invasive filamentous fungal infection (IFFI), a 3 mg/kg/day dose had a favourable overall response rate of 50% and 12 week survival rate of 72%. No improved outcome was seen with 10 mg/kg/day for the first 14 days. The study population was further analysed for the effect of prior azole exposure on treatment responses to liposomal amphotericin B. The protocol allowed prio…

Phase I/II study of pixantrone in combination with cyclophosphamide, vincristine, and prednisone in patients with relapsed aggressive non-Hodgkin lymphoma.

Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL). This phase I/II non-comparative study evaluated pixantrone in place of doxorubicin in the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), i.e. CPOP (cyclophosphamide, pixantrone, vincristine, and prednisone), in patients with relapsed aNHL who had previously received CHOP ± rituximab. Patients were administered pixantrone on day 1 of each 21-day cycle. Phase I (n = 35) dose escalation from 80 mg/m(2) to 180 mg/m(2) established the phase II (n = 30) dose as 150 mg/m(2). In phase II, 20 patients (67%) received all…

Preliminary Phase II Study Results of BBR2778 in Combination with Cyclophosphamide, Vincristine, and Prednisone in Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma.

Abstract Background: Pixantrone (BBR 2778) is a novel aza-anthracenedione with superior activity compared to doxorubicin and mitoxantrone in various tumor models including hematological malignancies. Pixantrone single agent therapy led to major responses in patients (pts) with aggressive lymphoma including diffuse large B-cell lymphoma (DLCL). The safety of a CHOP-like regimen with pixantrone replacing doxorubicin (CPOP) was assessed in a dose-ranging study indicating a recommended dose of 150 mg/m² for pixantrone. Method: In this phase II study the primary objective was to assess the efficacy of the CPOP regimen (cyclophosphamide 750 mg/m² d1, pixantrone 150mg/m² d1, vincristine 1.4mg/m² d…

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients.

OBJECTIVES: Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants. METHODS: Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified inten…

Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study.

Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neut…

Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Purpose Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease. Patients and Methods In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1:1:1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (P…

Supportive Efficacy Analyses for the Phase 3 Study of Temsirolimus Versus Investigator’s Choice Therapy for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma.

Abstract Temsirolimus (Torisel®) is a specific inhibitor of the mTOR kinase with antitumor activity in patients with relapsed or refractory mantle cell lymphoma. In a phase 3, randomized, open-label study, patients treated with temsirolimus 175 mg weekly 3 times followed by 75 mg weekly (175/75-mg) had significantly longer progression-free survival (PFS) than those treated with investigator’s choice therapy (p-value temsirolimus: investigator’s choice = 0.0009; hazard ratio = 0.44; 97.5% CI = 0.25, 0.78; Hess et al. J Clin Oncol.2008, 28:abs 8513). Patients treated with temsirolimus 175 mg weekly 3 times followed by 25 mg weekly (175/25-mg) showed a trend towards longer PFS than those treat…