Invasive aspergillosis survival, Voriconazole may be better than Amphotericin B

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Invasive aspergillosis survival, Voriconazole may be better than

Amphotericin B

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The retrospective analysis, published in the Clinical Infectious

Diseases, showed that patients who initially received antifungal

agent Vfend ( Voriconazole ) were more likely to survive than

patients who initially received Amphotericin B deoxycholate. The

analysis also showed that patients who started on Vfend were less

likely to need salvage therapy than those on Amphotericin B.

Salvage therapy is treatment given after the infection has not

responded to the initial treatment or if the patient cannot tolerate

the initial medicine.

Invasive aspergillosis is a severe pulmonary infection that can

occur in patients with weakened immune systems. The fatality rate

for invasive aspergillosis is estimated to be 58 percent, but

approaches 90 to 100 percent in patients whose infection has spread

beyond the primary site.

" These high mortality rates for invasive aspergillosis underscore

the importance of initial treatment for this often fatal infection, "

said F. , lead author of the analysis and at the

University of Texas Health Science Center at San . " Our

analysis demonstrates that Voriconazole's efficacy and tolerability

make it an important choice for first-line therapy. "

The Global Comparative Aspergillosis Study ( GCAS ) led to Vfend's

2002 approval for the first-line treatment of invasive aspergillosis

and was the basis for this newly published analysis.

In that study, 144 patients with confirmed or probable invasive

aspergillosis were started on Vfend and 133 were started on

Amphotericin B. If the disease progressed or the patient was unable

to tolerate initial therapy, treatment could be changed to salvage

therapy, which was referred to in the trial as " other licensed

antifungal therapy, " or OLAT.

Treatment was considered successful if the infection improved or was

cured after 12 weeks of total therapy. Therapies that were used as

salvage therapy included lipid formulations of Amphotericin B,

Itraconazole, a dose reduction in Amphotericin B, and other systemic

antifungal therapy.

et al retrospectively analyzed the data from the GCAS to

assess the effect of salvage therapy on patient outcomes. Their

analysis showed that just over a third ( 36 percent ) of patients in

the Vfend group required subsequent salvage therapy, while more than

three-quarters ( 80 percent ) of patients in the Amphotericin B

group required salvage therapy.

In addition, it found that of those patients in either group who had

to switch to salvage therapy, patients who started on Vfend had

better outcomes.

Patients in the Vfend group, who were switched to OLAT, were more

likely to survive than those in the Amphotericin B group who took

OLAT ( 48 percent versus 38 percent, respectively ).

Overall survival in the GCAS was 71 percent in the Vfend group

versus 58 percent in the Amphotericin B group.

Of patients who had to switch to OLAT due to drug intolerance, those

treated initially with Vfend had a higher success rate than those in

the Amphotericin B group ( 50 percent versus 38 percent,

respectively ) .

Of those who had to switch to OLAT due to their initial treatment

not working for them, patients initially treated with Vfend had a

higher success rate than those treated with Amphotericin B group (

26 percent versus 19 percent, respectively ).

In addition, 55 percent of patients treated with Vfend alone had a

successful outcome, compared to four percent of those on

Amphotericin B alone.

The overall efficacy rate was 53 percent for patients initially

treated with Vfend, versus 32 percent for patients initially treated

with Amphotericin B, regardless of whether OLAT was used.

It should be noted that lipid formulations of Amphotericin B are

often used due to their perceived reduction in toxicity. In the

GCAS, the lipid formulations were the most commonly used OLAT ( 38

percent of patients who received OLAT ).

However, the subsequent analysis of that study demonstrated that

this salvage therapy was effective in only 30 percent of patients in

the Amphotericin B group and 36 percent of patients in the Vfend

group.

This success rate decreased to 12 percent when lipid formulations of

Amphotericin B were used in patients following an initial

insufficient clinical response to Amphotericin B deoxycholate.

" Our analysis concluded that in order to reduce mortality rates

associated with invasive aspergillosis, we need to rethink the

practice of relying on salvage therapy, including lipid formulations

of Amphotericin B, and focus more on making the right initial

treatment decision, " said .

Vfend is currently approved in the United States for the treatment

of invasive aspergillosis, esophageal candidiasis, candidemia in

nonneutropenic patients and certain Candida infections. Vfend is

also approved as salvage therapy for fungal infections caused by

pathogens Scedosporium apiospermum and Fusarium species.

Vfend is the only IV/oral antifungal specifically indicated for the

first-line treatment of mould and yeast infections.

Most frequently reported adverse events in therapeutic trials were

visual disturbances, fever, rash, vomiting, nausea, diarrhea,

headache, sepsis, peripheral edema, abdominal pain and respiratory

disorder.

Treatment-related adverse events that most often led to

discontinuation in clinical trials were elevated liver function

tests ( LFTs ), rash and visual disturbances.

Vfend treatment-related visual disturbances are common. The effect

of Vfend on visual function is not known if treatment continues

beyond 28 days.

Vfend is contraindicated with Terfenadine, Astemizole, Cisapride,

Pimozide, Quinidine ( since increased plasma concentrations for

these drugs can lead to QT prolongation and rare occurrences of

torsades de pointes ), Sirolimus, Rifampin, Rifabutin,

Carbamazepine, long-acting barbiturates, ergot alkaloids, Efavirenz

and Ritonavir ( 400 mg q12h ).

There have been uncommon cases of serious hepatic reactions during

treatment with Vfend ( clinical hepatitis, cholestasis and fulminant

hepatic failure, including fatalities ). LFTs should be evaluated at

the start of and during the course of therapy. Patients have rarely

developed serious cutaneous reactions, such as s-

syndrome, during treatment with Vfend.

Source: Clinical Infectious Diseases, 2005

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