Objective: Echinocandins exhibit concentration-dependent efficacy in animal models of mycosis (Winderhold et al, ICAAC 2003; Andes et al, AAC 2003). We sought to determine the safety and efficacy of high-dose caspofungin (HDCAS) therapy in cancer patients with invasive fungal infections (IFIs). Methods: We retrospectively evaluated patients during 2002 2004 who had received HD-CAS (100 mg daily) after obtaining IRB approval. All values are given in median Â± s.d. Results: Age was 46 Â± 18 years, 9 (41%) were men, 10 (45%) were neutropenic and APACHE II score was 15 Â± 5. All 22 patients (100%) had hematologic malignancies; 15 had leukemia. In 7 (32%) hematopoietic stem cell transplant recipients, 6 patientsreceived allogeneic grafts and 3 (14%) had acute graft-versus-host disease. Fifteen patients (68%) had refractory cancer. Six (27%) were receiving substantial dose systemic corticosteroids (> 600 mg equivalent prednisone dose) during antifungal therapy. The range of cumulative CAS dose was 3004400 mg per patient and numbers of HD-CAS doses were 21 Â± 17 (range, 360). Nine patients (41%) had definite IFIs, 6 (27%) sino-pulmonary infections (5 Aspergillus; 1 Scedosporium apiospermum) and 3 patients (14%) had disseminated disease (2 Fusarium and 1 Aspergillus fumigatus). In 13 patients (59%) with probable IFIs, 10 (45%) had fungal pneumonia and 3 (14%) with sino-pulmonary involvement. Twenty-one patients (95%) received HD-CAS in combination with another antifungal agent, 6 (27%) received HD-CAS upfront, whereas in 16 patients (72%) initial therapy included AmBisome, voriconazole, and conventional-dose CAS. The 12-week crude mortality was 41% and IFI-attributable deaths were 32%. Overall, HD-CAS was tolerated without serious adverse reactions; 2 patients (9%) developed fatal liver failure, which was deemed unrelated to HD-CAS. Conclusions: In our high-risk patient population HD-CAS in combination with other antifungals was well tolerated and appears to have favorable impact on short-term mortality in patients with invasive mycosis.
Full conference title:
- ECCMID 15th (2005)