Safety of high-dose caspofungin in 80 cancer patients and haematopoietic stem cell transplant recipients with invasive fungal infections

Abstract number: 1733_477

Safdar A., Rodriguez G., Al Akhrass F., Kontoyiannis D., Kantarjian H., Champlin R., Raad I.

Background: We recently reported safety of high-dose caspofungin (HD-CAP) (100 mg daily) in 34 cancer patients (Safdar A, et al. ICAAC 2005). This study was performed to evaluate safety of HD-CAP in additional 80 patients at our cancer centre.

Methods: Retrospective review of adverse events (AE) was undertaken after obtaining IRB approval in patients who have received 3 or more days of HD-CAP between August 2004 and April 2006. All values are given in median ± standard deviations.

Results: Leukaemia was common underlying malignancy (63%) and age was 52±14 years. Over half of the patients (54%) had refractory or relapsed cancer. Among 37 (46%) haematopoietic stem cell transplant (HSCT) recipients, 29 (36%) had received allogeneic graft transplantation; 12 of 17 patients with GVHD were receiving treatment for chronic GVHD. APACHE II score was 12±5 (range, 2 to 25) and 34% had proven invasive fungal infections (IFI). Ninety-one percent received HD-CAP in combination with another antifungal agent including, voriconazole (34%) and AmBisome (36%). The duration of HD-CAP was 12±24 (range, 3 to 161) doses. In attached table, interval increase in values between start and end of HD-CAP therapy are shown. In 2 patients (3%) serum bilirubin level doubled after receiving 5 and 22 doses of HD-CAP therapy; levels return to normal after treatment was discontinued. One patient (1%) developed reversible paresthesia.

Conclusions: Extended therapy with HD-CAP was tolerated without serious hepatic or renal impairment. Reversible hyperbilirubinaemia may infrequently occur during HD-CAP therapy.