Liposomal amphotericin B standard dose in combination with caspofungin versus liposomal amphotericin B high dose regimen for the treatment of invasive aspergillosis in immunocompromised patients: randomised pilot study (Combistrat Trial)
Abstract number: 1733_478
Caillot D., Thiébaut A., Herbrecht R., Pigneux A., de Botton S., Attal M., Bernard F., Larché J., Alfandari S., Monchecourt F., Mahi L.
Objectives: Antifungal Monotherapy for Invasive Aspergillosis (IA) treatment is still associated with substantial mortality. Preclinical studies data suggest that combination therapy with polyenes and echinocandins may have additive activity against Aspergillus species.
Methods: We assessed the efficacy of Liposomal Amphotericin B standard dose (3 mg/kg/d) in combination with caspofungin standard dose (COMBO) versus Liposomal Amphotericin B high dose (10 mg/kg/d) regimen (L-AMB HD). Modified EORTC-MSG criteria were used to include patients with proven or probable IA. Study drug was administered until investigator-defined end of treatment (EOT). The primary endpoint was favourable overall response (FOR) defined as partial or complete response assessed at EOT. Survival was followed up to 12 weeks. Centrally data review committee confirmed IA diagnosis.
Results: 30 patients with pulmonary IA diagnosis were assessed: 15 received COMBO and 15 L-AMB HD. Groups were well matched in terms of demographics and neutropenia. Median duration of study drug treatment was COMBO 18 days  and L-AMB HD 17 days . At EOT, FOR was COMBO 67% vs. L-AMB HD 27% (p = 0.028). At week 12, FOR was 80% for COMBO and 67% for L-AMB HD (NS) and survival 100% COMBO vs. 86.7% L-AMB HD (NS). Infusion related reactions were observed in 3 L-AMB HD patients (20%) (Flush, cervical or thoracic pain, chills, nausea). Nephrotoxicity (serum creatinine >2x baseline) occurred in 4 L-AMB HD patients (23%) vs. 1 COMBO (7%). Hypokalaemia (K+ < 3.0 mmol/L) developed in 3 L-AMB HD (20%) vs. 2 COMBO (13%).
Assessment of volume and number of lesions observed in chest CT-Scan showed an increase and worsening at day 7 then a decrease until EOT (see Table1). These data support the initial diagnosis and allowed an optimal follow up of the pulmonary IA.
Conclusion: In immunocompromised patients with underlying haematological malignancies, Liposomal Amphotericin B at 3 mg/kg/d in combination with caspofungin showed promising results in initial treatment of invasive aspergillosis. A large randomised controlled trial is required to confirm these data. In addition the systematic use of chest CT-Scan appeared to be a useful tool to follow the evolution of pulmonary IA.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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