title: High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation.
abstract: Pneumocandins have concentration-dependent antifungal activity and higher dose of caspofungin (HD-CAP) in combination with other licensed antifungal therapy (OLAT) may improve response. Thirty-four patients who received HD-CAP were compared with 63 patients who received standard dose (SD)-CAP. There were no differences between the groups in either patient or disease characteristics. Significantly more patients in the HD-CAP arm had extrapulmonary infections (29 vs 8% in SD group; P=0.0053), and non-Aspergillus species infection (21 vs 6%; P=0.05) and had received prior antifungal therapy (71 vs 33%; P=0.0004). No serious adverse reactions were noted in patients receiving HD- or SD-CAP therapy. Twelve weeks after treatment commenced 44% had a complete or partial response compared with 29% in SD-CAP group (P=0.1). Logistic regression analysis showed a significant probability of a favorable outcome at 12 weeks in patients who received HD-CAP (OR 3.066, 95% CI, 1.092-8.61; P=0.033). This may in part reflect higher number of patients in HD group had received granulocyte-macrophage colony-stimulating factor (41 vs 14% in SD group; P=0.04) and/or interferon gamma (26 vs 5% in SD group; P=0.003) immune enhancement. Further studies are needed to evaluate efficacy of HD-CAP in severely immunosuppressed cancer patients with invasive fungal infections.
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, MD Anderson Cancer Center, Houston, TX 77030, USA. asafdar@mdanderson.org
authors.forename: A
authors.initials: A
authors.lastname: Safdar
authors.forename: G
authors.initials: G
authors.lastname: Rodriguez
authors.forename: K V I
authors.initials: KV
authors.lastname: Rolston
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: I F
authors.initials: IF
authors.lastname: Khouri
authors.forename: E J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: M J
authors.initials: MJ
authors.lastname: Keating
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
authors.forename: I I
authors.initials: II
authors.lastname: Raad
authors.forename: D P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use* / Q000633:toxicity; D000077336:Caspofungin; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007239:Infections / Q000139:chemically induced; D007371:Interferon-gamma / Q000627:therapeutic use; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000633:toxicity; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077336:Caspofungin