• Infectious Disease Clinical Trials
• Fungal Infections

• Infectious Disease Clinical Trials
• Infectious Disease
• Fungal Infections

Judith M. Martin, MD, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA, presented data from 2 studies that evaluated the safety and efficacy of voriconazole in pediatric patients with invasive candidiasis (IC), esophageal candidiasis (EC), and invasive aspergillosis (IA).

The incidence of invasive fungal infections has increased during the past 20 years in pediatric patients, with immunocompromised patients at an increased risk. Importantly, there are limited antifungal agents approved for use in pediatric patients. The triazole antifungal agent, voriconazole, has been demonstrated to be effective in adult patients with IC, EC, and IA [Ally R et al. Clin Infect Dis. 2001; Herbrecht R et al. N Engl J Med. 2002; Kullberg BJ et al. Lancet. 2005]. The purpose of these studies was to evaluate the safety and efficacy of voriconazole in pediatric patients with IC, EC, or IA.

Voriconazole was evaluated in 2 prospective, open-label, nonrandomized trials. The IC-EC trial had 22 patients, and the IA trial had 31 patients, all aged 2 to < 18 years. Of these 53 patients, 7 had confirmed IC, 10 had confirmed EC, and 14 had confirmed IA, using the Europe Organization for Research and Treatment of Cancer (EORTC) criteria. The dosing scheme for both trials is shown in Table 1. The duration of treatment was a minimum of 7 days after the last positive culture or 14 days after resolution of symptoms in patients with IC or EC, respectively, and 6 weeks in patients with IA.

The mean age was 9.5 years in the IC-EC study and 11.9 years in the IA study. Comorbid clinical conditions included blood and lymphatic system disorders, cardiac disorders, hepatobiliary disorders, neoplasms, and renal disorders. The mean duration of voriconazole therapy was 14 days in the IC-EC study and 49 days in the IA study.

The efficacy end point in the IC-EC study was the global response success rate (GRSR), defined as clinical cure or improvement and confirmed or presumed microbiologic eradication at the end of treatment (EOT); all-cause mortality was assessed at day 28 and EOT. In the modified intention-to-treat (mITT) population, the GRSR was 88.9% (95% CI, 51.75 to 99.72) in patients aged 2 to 11 years (n = 9) and 62.5% (95% CI, 24.49 to 91.48) in patients aged 12 to 17 years (n = 8). The GRSR by pathogen in the IC-EC study is shown in Table 2.

In the IA study, the efficacy end point was the GRSR, defined as clinical resolution or improvement of signs and symptoms plus complete or partial resolution of radiologic findings in patients with proven or probable IA, and it was assessed at weeks 6 and 12 (Table 3).

In the IC-EC trial, there were no deaths. In the IA trial, there were 5 deaths from any cause; 3 patients aged 2 to 11 years and 1 patient aged 12 to 17 years at 6 weeks, and 1 patient aged 12 to 17 years at EOT. None of the deaths were attributed to the treatment. In the IC-EC study, the most common treatment-related adverse events (TRAEs) were photophobia in 3 patients and rash in 2 patients; TRAEs leading to discontinuation of the study treatment occurred in 3 patients. In the IA study, the most common TRAEs were photophobia in 2 patients, blurred vision in 3 patients, increased alanine aminotransferase in 2 patients, abnormal liver function test results in 2 patients, and increased transaminases in 2 patients; also, 2 patients had serious adverse events related to treatment (acute renal failure and drug-induced liver injury).

The investigators concluded that the data from these analyses suggest that treatment of pediatric IC, EC, or IA with voriconazole was safe and effective, and consistent with previous studies in adults.

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