Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Trenschel, Rudolf; Ditschkowski, Markus; Elmaagacli, AH; Koldehoff, Michael; Ottinger, Hellmut; Steckel, Nina K.; Hlinka, M.; Peceny, Rudolf; Pm, Rath; Dermoumi, Heide; Dw, Beelen

doi:10.1038/sj.bmt.1704859

Cited by 35 publications

(26 citation statements)

References 15 publications

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“…However, in contrast to one small case series (29), there was no signal for increased hepatotoxicity in this randomized comparison, which is supported by retrospective postmarketing series that found no serious hepatic events with the concomitant use of caspofungin and cyclosporine (17,27,35,41).…”

Section: Discussionmentioning

confidence: 80%

Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

Groll

Silling

Young³

et al. 2010

Antimicrob Agents Chemother

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The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB (P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.Invasive opportunistic fungal infections are an important cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Depending on the presence of well-characterized risk factors, rates of infection by opportunistic fungal pathogens are between 10 and 25%. The case fatality rates vary between 35 and 50% for invasive candidiasis and 65 and 90% for invasive aspergillosis and infections by other filamentous fungi (8, 15).The existence of antifungal agents with different molecular targets is providing new opportunities to improve the efficacy of antifungal chemotherapy through combination therapy. Potential target populations include profoundly immunocompromised patients with prolonged granulocytopenia or following allogeneic hematopoietic stem cell transplantation, patients with fulminant or refractory infections, or those with infections in compartments that are difficult to treat and infections by fungal pathogens with decreased microbiological susceptibility (23,31,39,48,49,50).Based on its favorable microbiologic and pharmacokinetic properties (16), well-documented efficacy against Candida and Aspergillus infections, and excellent safety (24,28,32,45), the echinocandin lipop...

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Section: Discussionmentioning

confidence: 80%

Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

Groll

Silling

Young³

et al. 2010

Antimicrob Agents Chemother

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“…Clinically significant AST/ALT elevations were not observed, and no patient had drug interruption due to severe adverse events. In a further study, Trenschel et al [27] reported their experience in a matched pair analyse in 31 bone marrow transplanted patients (17 patients treated with CAS, 14 patients control group). Median duration time with CAS was 14 days.…”

Section: Discussionmentioning

confidence: 97%

Safety Profile of Concomitant Use of Caspofungin and Cyclosporine or Tacrolimus in Liver Transplant Patients

Saner

Gensicke

Rath³

et al. 2006

Infection

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“…Other retrospective studies in liver transplant patients, HSCT recipients and in patients after solid organ transplantation also did not reveal a major hepatic risk associated with concomitant administration of caspofungin and CYA. 17,19,[45][46][47] However, a retrospective evaluation of hepatic drug safety is limited, as hepatic dysfunction after allogeneic HSCT is common, occurring in 84% of patients, and may be because of a variety of causes such as GVHD, infections such as viral hepatitis, hepatic venoocclusive disease and/or recurrence of underlying disease. 48 Owing to the retrospective study design, ADEs affecting organs other than the liver or kidney were not assessed, as a systematic evaluation of patients could not be guaranteed.…”

Section: Discussionmentioning

confidence: 99%

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

Egger

Meier

Leu

et al. 2009

Bone Marrow Transplant

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The aim of this study was to assess the frequency of potential drug-drug interactions (pDDIs) and adverse drug events (ADEs) associated with antimycotics in hospitalized patients with hematopoietic SCT (HSCT). Of the 120 HSCT recipients evaluated, 36 received antimycotics. A total of 124 ADEs were recorded in 32 of the 36 patients treated, with 54 ADEs being possibly and 9 probably related to antimycotics. Of the treatments with amphotericin B, 93% were associated with one or more possible and 36% with probable ADEs. The corresponding figures for lipid-based amphotericin B were 100% and 7%, for voriconazole 68% and 11% and for caspofungin 70% and 0%. A total of 57 potentially severe DDIs associated with antimycotics were detected in 31 of the 36 patients. Of these, 14 DDIs were a possible cause of an ADE and 5 (4 times a combination of voriconazole with CYA and once a combination of CYA with conventional amphotericin B) were probably related. Although the prevalence of pDDIs and ADEs is high in HSCT patients, ADEs related with a high probability to treatment with antimycotics are rare. Regarding the high prevalence of pDDIs, our findings underscore the importance of close monitoring of laboratory and clinical parameters, as well as dose adjustment for critical drugs, in patients with HSCT.

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Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Cited by 35 publications

References 15 publications

Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

Safety Profile of Concomitant Use of Caspofungin and Cyclosporine or Tacrolimus in Liver Transplant Patients

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

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