title: Phase I/II study of pixantrone in combination with cyclophosphamide, vincristine, and prednisone in patients with relapsed aggressive non-Hodgkin lymphoma.
abstract: Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL). This phase I/II non-comparative study evaluated pixantrone in place of doxorubicin in the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), i.e. CPOP (cyclophosphamide, pixantrone, vincristine, and prednisone), in patients with relapsed aNHL who had previously received CHOP ± rituximab. Patients were administered pixantrone on day 1 of each 21-day cycle. Phase I (n = 35) dose escalation from 80 mg/m(2) to 180 mg/m(2) established the phase II (n = 30) dose as 150 mg/m(2). In phase II, 20 patients (67%) received all six planned cycles. The objective response rate was 73%, complete response/complete response unconfirmed (CR/CRu) rate was 47%, and median overall survival was 17.9 months. Myelosuppression was nearly universal. Six patients (20%) developed febrile neutropenia. Overall, left ventricular ejection fraction (LVEF) declines ≥10% occurred in 14 patients; declines seemed transient and unrelated to dose. Symptomatic cardiac failure occurred in four patients; however, pre-existing conditions confounded causality.
authors: Klinik I für Innere Medizin, Universität Köln, Köln, Germany.
authors: Peter
authors: P
authors: Borchmann
authors: Raoul
authors: R
authors: Herbrecht
authors: Martin
authors: M
authors: Wilhelm
authors: Franck
authors: F
authors: Morschhauser
authors: Georg
authors: G
authors: Hess
authors: Paul
authors: P
authors: Cernohous
authors: Susan A
authors: SA
authors: Veals
authors: Jack W
authors: JW
authors: Singer
authors: Andreas
authors: A
authors: Engert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007546:Isoquinolines / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D007546:Isoquinolines; D014750:Vincristine; D003520:Cyclophosphamide; C086548:pixantrone; D011241:Prednisone