TORONTOPreliminary clinical trial results show that treatment
with caspofungin acetate (Cancidas, investigational) produced a
favorable response in 41% of patients with life-threatening invasive
aspergillosis who were not responding to or were intolerant of other
Thomas Walsh, MD, chief, Immuno-compromised Host Section, National
Cancer Institute, Bethesda, presented the study results at the 40th
meeting of the Interscience Conference on Antimicrobial Agents and
Caspofungin is an echinocandin known as a glucan synthesis inhibitor
that is being developed by Merck & Co., Inc. to treat serious
fungal infections in adults.
We are encouraged by the results of this clinical study in this
extremely difficult-to-treat systemic infection, Dr. Walsh
said. Prognosis is usually poor in seriously ill patients with
pulmonary or extrapulmonary invasive aspergillosis who are not
responding to initial therapy and with underlying conditions such as
hematopoietic stem cell or organ transplantations.
Patients in the multicenter, noncom-parative study were
immunocompro-mised, had documented invasive aspergillosis, and were
not responding to or intolerant of prior antifungal therapy.
Of the 56 patients, 46 (82%) were refractory (unresponsive) to
previous therapy as evidenced by either progression of disease or
failure to respond to at least 7 days of prior antifungal therapy.
Ten patients (18%) were intolerant, defined as having creatinine
levels of 2.5 mg/dL or higher, or other acute reactions or
Underlying diseases included hematologic malignancies (25 patients),
allogeneic bone marrow trasnplant (14 patients), and other (17 patients).
A favorable response (complete or partial response) was defined as
the resolution or clinically meaningful improvement of all
attributable signs and symptoms as documented by radiographs and
judged by an independent expert panel of physicians.
Patients received 70 mg of caspofungin on day 1, followed by 50 mg
once daily thereafter, for a minimum of 28 days and for at least 7
days after resolution of symptoms. Duration of treatment was based on
the severity of the patients underlying disease, recovery from
immunosuppression, and onset of clinical response.
A favorable response was seen in 41% of patients receiving
caspofungin (22 of 54 patients who met entry criteria and had
outcomes data). For patients receiving more than 7 days of therapy,
the response rate was 49% (22 of 45).
The response rate was 34% (15 of 44) in refractory patients and 70%
(7 of 10) in intolerant patients.
Among patients with pulmonary disease, 18 of 40 (45%) had a favorable
response. Two (20%) of the 10 patients with disseminated disease
responded, as did two (50%) of the four patients with single-organ diseases.
Caspofungin, dosed for 1 to 160 days, was generally well tolerated,
Dr. Walsh said. Two serious adverse events were reported as possibly
drug-related (bilateral pulmonary infiltrates and hypercalcemia).
Infusion-related reactions and nephrotoxicities were uncommon. Three
patients (5.2%) discontinued use due to drug-related adverse events.
Several in vitro studies of caspofungin were also presented at the
ICAAC meeting. One study showed that the combination of caspofungin
and amphotericin B produced a synergistic result in more than half of Aspergillus
and Fusarium isolates tested.
Another study showed that the agent had in vitro activity across nine
different types of Candida species found in 1,808 isolates taken from
51 patients. The isolates included C albicans (1,388), C
guilliermondii (59), C krusei (25), C parapsilosis (54),
C kefyr (1), C tropicalis (78), C lipolytica
(8), C lusitaniae (2), and C glabrata (193).
In a test of 86 Aspergillus isolates obtained from 34 patients,
caspofungin showed potent activity, based on 24-hour MIC80,
against A fumigatus, A flavus, A niger, and A terreus.