Jørgensen, K.J., Gøtzsche, P.C., Dalbøge, C.S., & Johansen, H.K. (2014). Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia. Cochrane Database of Systematic Reviews, 2014(2).

DOI Link

Purpose

STUDY PURPOSE: To compare the benefits and harms of voriconazole with amphotericin B and fluconazole for the prevention or treatment of invasive fungal infections in patients with cancer who are neutropenic
 
TYPE OF STUDY: General review and semi-systematic review

Search Strategy

DATABASES USED: Cochrane Central Register of Controlled Trials (2014), MEDLINE (to January 2014), letters, abstracts, and unpublished trials in addition to contact with trial authors and industries
 
KEYWORDS: Amphotericin B (adverse effects, therapeutic use), antifungal agents (adverse effects, therapeutic use), aspergillosis (drug therapy), fluconazole (adverse effects, therapeutic use), liposomes; mycoses (drug therapy), neoplasms (complications), neutropenia (drug therapy, microbiology), opportunistic infections (drug therapy), pyrimidines (adverse effects, therapeutic use), randomized controlled trials as topic, triazoles (adverse effects, therapeutic use), humans
 
INCLUSION CRITERIA: Randomized clinical trials comparing voriconazole with amphotericin B or fluconazole
 
EXCLUSION CRITERIA: Trials solely concerned with the prevention or treatment of oral candidiasis and trials using inadequate randomization methods such as allocation based on date of birth

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 4
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Using the specific search terms described above, articles were selected and evaluated separately due to the heterogeneity of the trial designs in each article that met the criteria. For each study, the researchers evaluated the effectiveness of voriconazole compared to amphotericin B or fluconazole. They also took into consideration the risk of bias in the studies. Outcomes evaluated included mortality, invasive fungal infections, and other adverse effects (i.e., reasons for having to discontinue therapy, visual disturbances, dyspnea, hypokalemia). The researchers identified a deficit in trials being conducted to compare these commonly used antifungal agents.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 3
  • TOTAL PATIENTS INCLUDED IN REVIEW = 391
  • SAMPLE RANGE ACROSS STUDIES: 849–1,840 patients
  • KEY SAMPLE CHARACTERISTICS: Two studies included immunosuppressed men and women with cancer and the third investigated immunosuppressed men and women with cancer who had undergone allogeneic hematopoietic cell transplantations (HCTs).

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results

A trial comparing voriconazole to liposomal amphotericin B as an empirical treatment for suspected fungal infection in neutropenic patients with cancer in which 6.8% of the patients died showed a significant benefit of using liposomal amphotericin B over voriconazole. No benefits were found between antifungal agents in the other two trials evaluated.

Conclusions

For the empirical treatment of patients with cancer who are immunosuppressed, liposomal amphotericin B is significantly more effective than voriconazole. Voriconazole and fluconazole did not have different outcomes in patients undergoing allogeneic HCT who were given either of these antifungal agents prophylactically. Treatment of aspergillosis comparing voriconazole with amphotericin B was not investigated.

Limitations

Overall, there were so few trials comparing these antifungal agents (though large sample sizes) that except for one finding, results were inconclusive. These trials also could not be pooled for analysis due to their heterogeneity in study design.

Nursing Implications

For treatment of suspected fungal infections (neutropenic fever without overt fungal infection), liposomal amphotericin B is recommended. Careful evaluation for side effects of visual disturbances, dyspnea, and hypokalemia is critical.

Legacy ID

4839