Cancidas (caspofungin acetate)  - 4 Indications

Scroll down for more information on each indication:

• for the treatment of invasive aspergillosis; approved January 2001
• for the treatment of esophageal candidiasis; approved September 2002
• for the treatment of candidemia and the following Candida infections: intra-abdominal abscesses, peritonitis and pleural space infections; approved January 2003
• for empirical therapy of presumed fungal infections in febrile, neutropenic patients; approved September 2004

General Information

Cancidas is an echinocandin antifungal.

Cancidas is specifically indicated for adults and pediatric patients (3 months of age and older) for the following:

• Empirical therapy for presumed fungal infections in febrile, neutropenic patients
• Treatment of candidemia and the following Candida infections: intraabdominal abscesses, peritonitis and pleural space infections
• Treatment of esophageal candidiasis
• Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies

Cancidas is supplied as an injection for intravenous use. Administer by slow intravenous (IV) infusion over approximately 1 hour. Do not administer by IV bolus administration.

Dosage in Adults 18 years of age and older

• Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily for all indications except esophageal candidiasis.
• For esophageal candidiasis, use 50 mg once daily with no loading dose.

Dosage in Pediatric Patients 3 months to 17 years of age

• Dosing should be based on the patient’s body surface area.
• For all indications, administer a single 70-mg/m2 loading dose on Day 1, followed by 50 mg/m2 once daily thereafter.
• Maximum loading dose and daily maintenance dose should not exceed 70 mg, regardless of the patient's calculated dose. 

Mechanism of Action

Caspofungin is an echinocandin antifungal drug. Caspofungin inhibits the synthesis of beta (1,3)-D-glucan, an essential component of the cell wall of susceptible Aspergillus species and Candida species. Beta (1,3)-D-glucan is not present in mammalian cells. Caspofungin has shown activity against Candida species and in regions of active cell growth of the hyphae of Aspergillus fumigatus.

Side Effects

Adverse effects associated with the use of Cancidas in adults may include, but are not limited to, the following:

• diarrhea
• pyrexia
• ALT/AST increased
• blood alkaline phosphatase increased
• blood potassium decreased

Adverse effects associated with the use of Cancidas in pediatrics may include, but are not limited to, the following:

• pyrexia
• diarrhea
• rash
• ALT/AST increased
• blood potassium decreased
• hypotension
• chills

Indication 1 - for the treatment of invasive aspergillosis

approved January 2001

Clinical Trial Results

The effectiveness of Cancidas was assessed in a small, multi-center, open-label, non-comparative study involving 69 patients with invasive aspergillosis. Patients were between the ages of 18 and 80 and had been intolerant to other antifungal therapies. A favorable response to Cancidas treatment was defined as either complete response or clinically meaningful improvement and was determined by an independent expert panel. The panel determined that 41% of patients who received at least one dose of Cancidas elicited a favorable response and those receiving more than seven days of treatment had a 50% favorable response rate.

Indication 2 - for the treatment of esophageal candidiasis

approved September 2002

Clinical Trial Results

The safety and efficacy of Cancidas in the treatment of esophageal candidiasis was evaluated in one large, controlled, noninferiority, clinical trial and two smaller dose-response studies. In all 3 studies, patients were required to have symptoms and microbiological documentation of esophageal candidiasis; most patients had advanced AIDS (with CD4 counts <50/mm3 ). In the large, randomized, double-blind study comparing Cancidas 50 mg/day versus intravenous fluconazole 200 mg/day for the treatment of esophageal candidiasis, patients were treated for an average of 9 days (range 7-21 days). Favorable overall response at 5 to 7 days following discontinuation of study therapy required both complete resolution of symptoms and significant endoscopic improvement. The definition of endoscopic response was based on severity of disease at baseline using a 4-grade scale and required at least a two-grade reduction from baseline endoscopic score or reduction to grade 0 for patients with a baseline score of 2 or less. The proportion of patients with a favorable overall response was comparable for Cancidas and fluconazole. The proportion of patients with a favorable symptom response was also comparable (90.1% and 89.4% for Cancidas and fluconazole, respectively). In addition, the proportion of patients with a favorable endoscopic response was comparable (85.2% and 86.2% for Cancidas and fluconazole, respectively). The esophageal candidiasis relapse rates at the Day 14 post-treatment visit were similar for the two groups. At the Day 28 post-treatment visit, the group treated with Cancidas had a numerically higher incidence of relapse; however, the difference was not statistically significant. The results from the two smaller dose-ranging studies corroborate the efficacy of Cancidas for esophageal candidiasis that was demonstrated in the larger study.

Indication 3 - for the treatment of candidemia and the following Candida infections: intra-abdominal abscesses, peritonitis and pleural space infections

approved January 2003

Clinical Trial Results

In a randomized, double-blind study, patients with a proven diagnosis of invasive candidiasis received daily doses of Cancidas (50 mg/day following a 70-mg loading dose on Day 1) or amphotericin B deoxycholate (0.6 to 0.7 mg/kg/day for non-neutropenic patients and 0.7 to 1 mg/kg/day for neutropenic patients). Patients who met the entry criteria and received one or more doses of IV study therapy were included in the modified intention-to-treat [MITT] analysis of response at the end of IV study therapy. A favorable response at this time point required both symptom/sign resolution/improvement and microbiological clearance of the Candida infection. Two hundred thirty-nine patients were enrolled. Of the 239 patients enrolled, 224 met the criteria for inclusion in the MITT population. At the end of IV study therapy, Cancidas was comparable to amphotericin B in the treatment of candidemia in the MITT population. For the other efficacy time points (Day 10 of IV study therapy, end of all antifungal therapy, 2-week post-therapy follow-up, and 6- to 8-week post-therapy follow-up), Cancidas was as effective as amphotericin B.

Indication 4 - for empirical therapy of presumed fungal infections in febrile, neutropenic patients

approved September 2004

Clinical Trial Results

A double-blind study enrolled 1111 febrile, neutropenic (<500 cells/mm3 ) patients who were randomized to treatment with daily doses of Cancidas (50 mg/day following a 70-mg loading dose on Day 1) or AmBisome (3 mg/kg/day). Patients were stratified based on risk category (high-risk patients had undergone allogeneic stem cell transplantation or had relapsed acute leukemia) and on receipt of prior antifungal prophylaxis. Twenty-four percent of patients were high risk and 56% had received prior antifungal prophylaxis. Patients who remained febrile or clinically deteriorated following 5 days of therapy could receive 70 mg/day of Cancidas or 5 mg/kg/day of AmBisome. Treatment was continued to resolution of neutropenia (but not beyond 28 days unless a fungal infection was documented). An overall favorable response required meeting each of the following criteria: no documented breakthrough fungal infections up to 7 days after completion of treatment, survival for 7 days after completion of study therapy, no discontinuation of the study drug because of drug-related toxicity or lack of efficacy, resolution of fever during the period of neutropenia, and successful treatment of any documented baseline fungal infection. Based on the composite response rates, Cancidas was as effective as AmBisome in empirical therapy of persistent febrile neutropenia. The rate of successful treatment of documented baseline infections, a component of the primary endpoint, was not statistically different between treatment groups.