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.