Invasive Candidiasis in Cancer Patients: Observations From a Randomized Clinical Trial

J Infect. 2005 Jun;50(5):443-9. doi: 10.1016/j.jinf.2005.01.016.

Abstract

Background: Invasive candidiasis is a common and serious complication of cancer and its therapy.

Methods: We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication.

Results: 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors.

Conclusions: Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amphotericin B / administration & dosage
  • Amphotericin B / adverse effects
  • Amphotericin B / therapeutic use*
  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use*
  • Candida / isolation & purification
  • Candidiasis / drug therapy*
  • Candidiasis / etiology*
  • Caspofungin
  • Echinocandins
  • Female
  • Fungemia
  • Gastrointestinal Neoplasms / complications*
  • Hematologic Neoplasms / complications*
  • Humans
  • Leukemia / complications
  • Lipopeptides
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Neutropenia / chemically induced
  • Peptides, Cyclic / adverse effects
  • Peptides, Cyclic / therapeutic use*
  • Retrospective Studies
  • Species Specificity
  • United States

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Peptides, Cyclic
  • Amphotericin B
  • Caspofungin