Empirical Antifungal Therapy (Rx) with Caspofungin (CAS) vs Liposomal Amphotericin B (L-AmB) for Persistently Febrile Neutropenic Patients (Pts) with Acute Myeloid Leukemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1337-1337 ◽  
Author(s):  
Johan A. Maertens ◽  
Hedy Teppler ◽  
Robert Lupinacci ◽  
Michael Bourque ◽  
Mark DiNubile ◽  
...  
Keyword(s):  
High Risk ◽  
Study Drug ◽  
Antifungal Prophylaxis ◽  
Successful Outcome ◽  
Risk Category ◽  
Cell Transplant ◽  
Success Rates ◽  
Double Blind ◽  
Hematopoietic Stem ◽  
Post Hoc

Abstract Background: In a double-blind randomized trial of empirical antifungal Rx for persistently febrile neutropenic pts, CAS was as effective as and better tolerated than L-AmB. We now examine the results of this study in the subgroup of pts with AML. Methods: Randomization to CAS (70 mg x 1, then 50 mg/d) or L-AmB (3 mg/kg/d) was stratified by risk category [high risk = allogeneic hematopoietic stem cell transplant or relapsed acute leukemia] and use of antifungal prophylaxis. The primary efficacy endpoint was % of treated pts with documented fever and neutropenia who had a successful outcome defined by all the following: successful Rx of baseline (BL) invasive fungal infection (IFI) (if any), no breakthrough (BT) IFI to 7 d post-Rx, survival @7d post-Rx, no premature discontinuation (DC) due to lack of efficacy or study drug toxicity, and fever resolution x 48 hr during neutropenia. Results: 703/1095 (64%) of the treated pts had AML, including 364/556 (65%) and 339/539 (63%) in the CAS and L-AmB groups, respectively. Demographic characteristics were similar in AML pts in both Rx groups. 27% of CAS and 22% of L-AmB pts with AML were high risk. Median days of Rx were: CAS, 12; L-AmB, 11. The table shows % AML pts with a successful outcome by Rx group. % AML pts with a successful outcome by Rx group CAS (N=364) L-AmB (N=339) Difference (CAS - L-AmB) 95% CI for difference between treatment groups † 7/14 CAS and 5/16 L-AmB pts had successful Rx of BL IFI. Success Rx of BL IFI † 50 31 19 (−16, 53) No BT IFI 93 95 −2 (−5, 2) Suvival @ 7d post-Rx 92 88 4 (0, 8) No premature DC 87 86 2 (−3, 7) Fever resolution 48 46 2 (−5, 9) All of the above 40 38 2 (−5, 10) The composite success rates for the high risk AML pts were 46/99 (46%) for CAS and 31/76 (41%) for L-AmB. Conclusions: In this post hoc subgroup analysis, CAS provided an effective and generally well-tolerated option for the empirical Rx of persistently febrile neutropenic pts with AML.

scholarly journals Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

1996 ◽  
Vol 40 (5) ◽  
pp. 1108-1115 ◽  
Author(s):  
A Cometta ◽  
T Calandra ◽  
H Gaya ◽  
S H Zinner ◽  
R de Bock ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Study Drug ◽  
Empiric Therapy ◽  
Successful Outcome ◽  
Combination Group ◽  
Monotherapy Group ◽  
Success Rates ◽  
Beta Lactams ◽  
European Organization ◽  
Gram Negative Bacteremia

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

Pharmacokinetics of Ganciclovir Following Oral Valganciclovir Versus Intravenous Ganciclovir in Allogeneic Hematopoietic Stem-Cell Transplant Patients with Stable Graft-Versus-Host Disease of the Gastrointestinal Tract.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2223-2223 ◽  
Author(s):  
Drew J. Winston ◽  
Voravit Ratanatharathorn ◽  
Lindsey Baden ◽  
Christos Emmanouilides ◽  
Don Gabriel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Creatinine Clearance ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Study Drug ◽  
Preemptive Therapy ◽  
Solid Organ ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Cytomegalovirus (CMV) disease can be effectively prevented in allogeneic hematopoietic stem cell transplant (HSCT) patients by ganciclovir (GCV) given as prophylaxis or preemptive therapy. Due to the low bioavailability of oral GCV capsules, GCV is usually administered intravenously (IV) to HSCT patients. Valganciclovir (VGCV) is the valine ester prodrug of ganciclovir. In healthy subjects, HIV-infected patients, and solid-organ transplants, the oral bioavailability of VGCV is about 60%, or 10-fold higher than oral GCV capsules. The bioavailability and total GCV exposure provided by oral VGCV relative to IV GCV in HSCT patients with gastrointestinal (GI) GHVD has not been established. METHODS: HSCT patients were eligible for the study if the following criteria were satisfied: 1) ≥16 years of age; 2) biopsy-proven GHVD of GI tract with nausea and/or diarrhea (300–1500 ml/day) or proven GVHD of skin or liver plus diarrhea with no other explanation; 3) no active CMV infection or disease; 4) neutrophil count ≥1000/μL; 5)creatinine clearance >60 ml/min. Following a standardized breakfast, eligible patients were randomized to receive a single dose of open-label study drug (900 mg of oral VGCV or 5 mg/kg of IV GCV). After a minimum 48 hr. washout period, patients were crossovered to alternate study drug. Blood for levels of GCV and VGCV were obtained predose and then over the 24 hours after dosing. Pharmacokinetic (PK) parameters were derived by noncompartmental methods. RESULTS: Data from 16 patients are currently available. Patient demographics include mean age 45 yrs (range 23 to 58 yrs); males 13, females 3; mean weight 80kg (range 52 to 107 kg); mean creatinine clearance 96 ml/min (range 62 to 184 ml/min). Median time after transplant for study was 303 days (range 102 to 988 days). Mean GCV PK parameters are summarized in the following table. Mean GCV Value (Coefficient of variation in %) Oral VGCV-900 mg IV GCV-5mg/kg Parameter N = 16 N = 16 AUC o -τ (μg•hr/mL) 43.58 (37) 46.74 (40) AUC o-∞ (μg•hr/mL) 46.03 (41) 48.89 (43) C(max) μg/mL) ( 6.45 (30) 12.53 (30) T max (hr) 3.13 (22) 0.97 (8) T½ (hr) 4.97 (31) 5.09 (29) GCV AUC values were similar, although maximum GCV concentrations were higher and acheived earlier with IV GCV. Terminal elimination half-life of GCV with oral VGCV and IV GCV were similar. After 900 mg of oral VGCV, mean plasma Cmax for VGCV was low (0.22 μg/mL), which is consistent with rapid and almost complete metabolism of VGCV to GCV. CONCLUSION: These preliminary results suggest that systemic exposure to GCV after 900 mg of oral VGCV is comparable to that achieved with IV GCV in HSCT patients with stable GI GVHD. Oral VGCV could be a useful alternative to IV GCV in certain HSCT patients requiring prophylaxis or preemptive therapy for CMV.

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