title: Invasive candidiasis in cancer patients: observations from a randomized clinical trial.
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.
authors.affiliation: Department of Clinical Research, Merck Research Laboratories, P.O. Box 4, BL3-4, West Point, PA 19486, USA. mark_dinubile@merck.com
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Darcy
authors.initials: D
authors.lastname: Hille
authors.forename: Carole A
authors.initials: CA
authors.lastname: Sable
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kartsonis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002175:Candida / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy* / Q000209:etiology*; D000077336:Caspofungin; D054714:Echinocandins; D005260:Female; D016469:Fungemia; D005770:Gastrointestinal Neoplasms / Q000150:complications*; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D007938:Leukemia / Q000150:complications; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013045:Species Specificity; D014481:United States
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077336:Caspofungin