Abstract
Outcomes for patients with non-Hodgkin’s lymphoma (NHL) that proves refractory to treatment remain poor. Treatment of such patients is individualized and can include enrolment in a clinical trial of novel agents or use of one of a wide array of drug regimens. Initial treatment with anthracyclines such as doxorubicin limits options at later stages of treatment because of anthracycline-related cumulative cardiotoxicity. The aza-anthracenedione pixantrone was developed to reduce the likelihood of cardiotoxicity without compromising efficacy and is currently conditionally approved for use as monotherapy in patients with multiply-relapsed or refractory aggressive B cell NHL. The use of pixantrone in combination therapy, often to replace doxorubicin or mitoxantrone, has or is currently being investigated in numerous studies in patients with aggressive or indolent NHL and is the focus of this review. These include the R-CPOP regimen (rituximab, cyclophosphamide, pixantrone, vincristine, prednisone) for aggressive NHL in the first-line setting, including a study in elderly patients with limited cardiac function, and for patients with relapsed NHL with prior anthracycline exposure; the PSHAP regimen (pixantrone, cytarabine, prednisone, cisplatin), also in the latter setting; the PREBen/PEBen regimen (pixantrone, bendamustine and etoposide with or without rituximab) as salvage therapy; and pixantrone in combination with fludarabine, dexamethasone, and rituximab (FPD-R) for relapsed indolent NHL.
Highlights
Pixantrone is a novel aza-anthracenedione, developed to reduce cardiotoxicity typically associated with anthracyclines but without compromising antineoplastic efficacy [1].Comprehensive Cancer Centre and University of Helsinki, Helsinki, Finland 4 Department of Hematology, Odense University Hospital, Odense, Denmark 5 Department of Hematology, Aarhus University Hospital, Aarhus, DenmarkAnthracenediones contain only three planar rings versus four of anthracyclines and lack the daunosamine amino-sugar that anthracyclines possess [2]
The study was discontinued earlier than expected due to low patient enrollment, the results suggested that pixantrone plus rituximab may be more effective than rituximab monotherapy in this patient population (ORR 75% vs 33%, Complete response (CR) 35% vs 11%, PR 40% vs 22% and time to progression: 13.2 vs 8.1 months) [18]
Treatment challenges remain in the management of relapsed aggressive non-Hodgkin’s lymphoma (NHL) as a there is a lack of regimens as effective as first-line therapy [11]
Summary
Pixantrone is a novel aza-anthracenedione, developed to reduce cardiotoxicity typically associated with anthracyclines but without compromising antineoplastic efficacy [1]. The NLG has used this combination (with rituximab in CD20+ tumors [PREBEN]) in 30 heavily pretreated patients with aggressive NHL (Table 1; data available as a poster) [13], with their findings informing subsequent clinical trial design, as well as by a Spanish group in five patients with refractory or relapsed DLBCL [26] These early results suggest that PREBEN/PEBEN is a feasible salvage regimen, with durable and substantial responses to treatment in individual patients (Table 2) [13]. Seven of eight patients with grade decreases in LVEF had previously received anthracyclines [19] This study reported a median PFS of 82 days after a median follow-up of 8.2 months; the median OS was not reached (both secondary endpoints) [43]
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