Cisplatin, fludarabine, and cytarabine: A novel, pharmacologically designed salvage therapy for patients with refractory, histologically aggressive or mantle cell non-Hodgkin lymphoma

Abstract

BACKGROUND. Based on in vitro synergism, the combination of cytarabine (ara-C) and cisplatin is the basis of many salvage regimens for patients with aggressive non-Hodgkin lymphoma (NHL). However, patients with previously refractory disease are significantly less likely to respond, stimulating the search for novel salvage regimens. In vitro, fludarabine enhances the cytotoxicity of both ara-C and cisplatin, increasing ara-C incorporation into DNA and inhibiting repair of platinum/DNA adducts, suggesting that the combination of cisplatin, fludarabine, and ara-C (PFA) may have clinical utility. METHODS. A Phase-II study of a 96-hour continuous infusion of cisplatin with two timed-sequential co..