Nonpegylated liposomal doxorubicin in the treatment of B-cell non-Hodgkin’s lymphoma: where we stand

Anthracyclines, including doxorubicin, are widely used in the treatment of B-cell non-Hodgkin's lymphoma (NHL). However, their clinical potential is limited by their cardiotoxic adverse effects, which include cardiomyopathy and congestive heart failure. Anthracycline-induced cardiotoxicity is cumulative and irreversible. Liposomal doxorubicin has been developed with the aim of improving the therapeutic index of doxorubicin by reducing the drug's cardiotoxicity. Nevertheless, liposomal conjugation of doxorubicin results in preferential distribution of the drug in the tumor compared with normal tissue, maintaining its anti-tumor efficacy. Nonpegylated liposomal doxorubicin produced a promising response rate when substituted for conventional doxorubicin in the cyclophosphamide, doxorubicin, vincristine and prednisolone regimen in the treatment of patients with NHL either at diagnosis or at relapse. The ability of nonpegylated liposomal doxorubicin to overcome excessive drug efflux due to P-glycoprotein (MDR-1) overexpression in NHL might confer on this drug a curative potential for patients with a bad prognosis (e.g., MDR-1 overexpressing, the elderly or frail).