Efficacy and safety of higher doses of caspofungin (CAS)

N. Kartsonis, H. Teppler, A. Ngai, M. Bourque, M. White, A. Williams-Diaz, A. Taylor, R. Lupinacci and C. Sable

Author address: 

Merck Res Labs, W Point, PA, USA

Abstract: 

Objectives: CAS is approved for use at 50 mg day-1 (with a 70-mg load on Day 1 for invasive fungal infections). In Phase I studies, single CAS doses up to 210 mg and multiple CAS doses up to 100 mg day-1 have been well tolerated. Herein, we review the CAS efficacy and safety at doses >50 mg day-1 in patients (pts) from phase IIIII experience. Methods: Ninety-six patients received CAS 70 or 100 mg day-1 as initial therapy in four clinical trials, including three esophageal candidiasis (EC) trials (Protocol 003 [P003], P004, P007) and an invasive aspergillosis (IA) study (P019). Efficacy: EC: three CAS doses (35, 50 and 70 mg day-1) were studied in EC. All pts had symptomatic, endoscopic and microbiological evidence of EC. A favorable clinical response required complete symptom resolution and substantial (2 grade) reduction in endoscopic lesions. IA: three CAS doses (50, 70, and 100 mg day-1) were sequentially evaluated in P019. All pts had proven/probable IA, refractory or intolerant to standard antifungal therapy (Rx). A favorable response (complete or partial) required significant clinical and radiographic improvement. In both EC and IA, efficacy was assessed using a modified-intention-to-treat (MITT) approach (1 CAS dose and documented fungal diagnosis).TABLESafety: Adverse events (AE) were collected from all pts with EC or IA. Investigators identified the seriousness, causality, and action on study Rx for all clinical and lab AE during Rx and for 14 days postRx. CAS safety data at higher doses (70 and 100 mg day-1) was compared with safety at lower doses (35 mg and 50 mg day-1) across all four studies. Results: Efficacy: In EC, the pt characteristics were similar across the three CAS doses. Higher success rates were noted at 50 and 70 mg day-1 (79 and 82%) vs. 35 mg day-1 (67%). In IA, the pt characteristics were also similar across the three doses. No efficacy differences were noted across the 50 and 70 mg groups (48 and 44% respectively). Data at the highest dose (100 mg day-1) were limited (2/6, 33%). Safety: Mean duration of CAS Rx in pts receiving 70 mg day-1 (n = 90) and 100 mg day-1 (n = 6) was 15.4 days (range 290) and 34.8 days (range 780) respectively. The AE incidence and safety profile was relatively similar among pts receiving either higher (70 mg day-1) or lower (50 mg day-1) CAS doses. Conclusion: CAS at doses up to 100 mg day-1 has been generally well tolerated. Additional safety and efficacy data at multiple doses up to 150 mg daily is currently being collected.
2005

abstract No: 

P027

Full conference title: 

2nd Trends in Medical Mycology
    • TIMM 2nd (2010)