Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Invasive Fungal Infections (IFI) remain a severe and major complication among patients with hematologic diseases, but the recent availability of new antifungal agents (echinocandins and new azoles) have improved the chance of cure. Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the enzyme complex 1,3-d-glucan synthetase; this action specifically damages the fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most Candida species and Aspergillus species. We report on our experience with this drug as first-line therapy for proven or probable pulmonary IFI in immunocompromised patients with hematologic malignancies. Thirty-two consecutive patients (20 males and 12 females, with a median age of 52 yr) have been treated with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease, while 12 patients were in complete remission and 4 were at onset of disease; 8/32 (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure. Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and 25 (78%) had a probable IFI with pulmonary localization as defined according to international consensus. Thirty-one patients (97%) had less than 1000 granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received concomitant granulocyte colony-stimulating factor (G-CSF). The overall response rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses; two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond and seven died of mycotic infection. Univariate analysis showed that granulocytes recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset vs. refractory/relapsed) were significantly associated to favourable outcome. No clinical adverse events (AE) were reported and only a grades I and II transient increase of serum alkaline phosphatase and/or transaminases occurred in 4/32 (12%) patients. After CAS therapy six non-responders and six cases with a partial or stable response were rescued with voriconazole. Two out of six patients (33%) in the former group and 6/6 (100%) in the latter obtained a complete resolution of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as first-line treatment of proven or probable IFI with pulmonary localization. The drug was well tolerated and there were no significant hepatic AE even in patients receiving CAS with cyclosporine after a HSCT. A significant proportion of non-responders or partial responders to CAS can be rescued with a subsequent voriconazole-based therapy.
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PMID:Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies. 1610 79

Infections and adverse drug reactions both contribute substantially to mortality after allogeneic stem cell transplantation. It is therefore crucial to the transplant physician to develop an optimal anti-infective strategy, i.e. one which is highly effective and shows few side effects. Caspofungin acetate, the founding member of the echinocandins, is widely used against invasive fungal infections. We retrospectively assessed the hepatotoxicity of caspofungin acetate when administered with cyclosporine A. We reviewed the medical charts of 20 recipients of an allogeneic transplant. In detail, the median value of alanine amino transferase before, during and after administration of caspofungin acetate was 0.39 [standard error of the mean (SEM) 0.65], 0.77 (17) and 0.56 (0.77) micromol l(-1). The maximal value was 4-, 104- and 3.3-fold the upper normal level. The median value of aspartate amino transferase was 0.28 (SEM 0.45), 0.71 (26.26) and 0.60 (0.84) micromol l(-1). The maximal value before, during and after the administration of caspofungin acetate was 3.6-, 203- and 5.3-fold the upper normal level. The median value of gamma glutamyl transferase before, during and after administration of caspofungin acetate was 1.27 (SEM 1.78), 2.33 (3.41) and 1.77 (4.32) micromol l(-1). The maximal value was 1.38-, 2.53- and 1.93-fold the upper normal level. The median value of alkaline phosphatase before, during and after administration of caspofungin acetate was 1.11 (SEM 0.4), 1.97 (2.30) and 1.66 (5.48) micromol l(-1). The maximal value was 0.88-, 4.2- and 8.42-fold the upper normal level, respectively. The median value of total bilirubin before, during and after administration of caspofungin acetate was 23 (SEM 19.69), 38 (55.41) and 20 (67.23) micromol l(-1). The maximal value was 4.18-, 14.18- and 17.88-fold the upper normal level. Taken together, the elevations observed fell after the discontinuation of caspofungin acetate. This report is in accordance with published data. As expected, we did not find any evidence pointing to an increase in nephrotoxicity by caspofungin acetate.
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PMID:Comedication of caspofungin acetate and cyclosporine A after allogeneic haematopoietic stem cell transplantation leads to negligible hepatotoxicity. 1847 Nov 57