title: Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with denileukin diftitox (ONTAK).
abstract: Cutaneous T-cell lymphoma (CTCL) can be associated with painful, pruritic, disfiguring lesions. As part of a multicenter, randomized phase III trial in patients with heavily pretreated advanced and/or recurrent CTCL, the effects of an interleukin-2 receptor-targeted fusion protein, denileukin diftitox (DAB389IL-2, ONTAK), on patient-rated overall quality of life (QOL), skin appearance, and pruritus severity were evaluated. A total of 71 patients with stage IB-IVA CTCL received intravenous denileukin diftitox 9 microg/kg/day or 18 microg/kg/day over 15-60 minutes for 5 consecutive days on an outpatient basis; cycles were planned for every 21 days for a total of 8 cycles over 6 months. Prior to each treatment cycle, patients were evaluated for disease response and were asked to self-rate their overall QOL via the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, skin appearance (7-point scale), and pruritus severity (10-cm visual analogue scale). Composite FACT-G and most individual subscale scores (physical, social/family, emotional, and functional well being) in documented responders (n = 21) gradually increased during the study period, generally reaching statistical significance (P < 0.05) by cycle 3, and were significantly (P < or = 0.041) higher than the scores of nonresponders at endpoint. Additionally for responders, assessments of skin severity and pruritus severity showed significant (P < or = 0.05) improvements at study endpoint compared with baseline. Adverse transfusion-related events (eg, hypersensitivity reactions, flu-like syndrome) were common during cycles 1 and 2, and vascular-leak syndrome occurred in 25% of patients. Denileukin diftitox was not associated with any clinically significant myelosuppression. Heavily pretreated patients with advanced and/or recurrent CTCL who responded to denileukin diftitox therapy showed significant improvements in self-rated overall QOL, skin appearance, and pruritus severity.
authors.affiliation: Department of Dermatology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. mduvic@mdanderson.org
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Elise A
authors.initials: EA
authors.lastname: Olsen
authors.forename: Ann G
authors.initials: AG
authors.lastname: Martin
authors.forename: Francine M
authors.initials: FM
authors.lastname: Foss
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Peter W
authors.initials: PW
authors.lastname: Heald
authors.forename: Patricia
authors.initials: P
authors.lastname: Bacha
authors.forename: Jean
authors.initials: J
authors.lastname: Nichols
authors.forename: Astra
authors.initials: A
authors.lastname: Liepa
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017060:Patient Satisfaction; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012016:Reference Values; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox