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This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: jmm.0.012401-0v1 58/11/1474    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Ellis, M. Articles by A. Stevens, D. PubMed PubMed Citation Articles by Ellis, M. Articles by A. Stevens, D. Agricola Articles by Ellis, M. Articles by A. Stevens, D.

A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever

¹ Department of Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE

² Department of Community Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE

³ Department of Oncology, Tawam–Johns Hopkins Hospital, Al Ain, UAE

⁴ Department of Medicine, Al-Ain Hospital, Al Ain, UAE

⁵ International Medical Affairs, Gilead Sciences, London, UK

⁶ Gilead Sciences, Foster City, CA, USA

⁷ Santa Clara Valley Medical Center, San Jose, CA, USA

Correspondence
Michael Ellis
michael.ellis{at}uaeu.ac.ae

Received May 3, 2009
Accepted July 9, 2009

A high intermittent dose regimen (group A: 10 mg kg^–1 on day 1, 5 mg kg^–1 on days 3 and 6) was compared with standard dosing (group B: 3 mg kg^–1 per day for 14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent febrile neutropenia. A total cumulative dose of 1275 mg (group A) and 2800 mg (group B) was administered. Infusion-related adverse drug events, mainly rigors/chills, occurred more frequently with group A (11/45, 24 % infusions) than with group B (12/201, 6 % infusions) (P=0.002), which extended the mean infusion time by 20 min (P=0.001). Creatinine levels were similar in the two regimens: the A : B ratio of the area under the curve for creatinine (AUC_CREATININE) for days 2–7 was 1.09 (P=0.27) and for days 2–14 was 1.05 (P=0.51). Rises in creatinine were mild (clinical toxicity criteria 1) in all patients with elevations. Hypokalaemia tended to be less severe in group A with a lower proportion of hypokalaemic days [57/143 (39 %) vs 80/137 (58 %), P=0.21], a higher AUC_POTASSIUM (A : B ratio of 1.06, P=0.12), a lower proportion of patients with hypokalaemia at the end of study (10 vs 61 %, P=0.01) and fewer potassium-supplemented days [12/210 (6 %) vs 41/210 (19.5 %), P<0.1]. There were mildly elevated median levels of serum bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, which were similar for the two regimens and were usually associated with other co-existing co-morbid conditions. The AUC for these enzymes was also similar in the two groups. No patient had discontinuation of the study drug due to toxicity. Composite success was identical for each regimen (11/15 patients, 73 %). Three of the fifteen patients in group B and none in group A developed invasive fungal infections (IFIs). β-D-Glucan levels were similar in both groups for patients without an IFI [AUC_GLUCAN of 362 and 683 (P=0.36) for groups A and B, respectively]. The rate of defervescence was similar for each regimen (P=0.75). This feasibility study suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg^–1 on days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg kg^–1 per day, with drug-acquisition cost savings and reduced drug exposure. A larger study is indicated for confirmation of this.

Tables and figures of additional data are available as supplementary material with the online version of this paper.