Pharmacokinetic evaluation of vincristine for the treatment of lymphoid malignancies.

INTRODUCTION: Vincristine is a key agent for the treatment of acute lymphoblastic leukemia (ALL) and other lymphoid malignancies. The strong antineoplastic activity of vincristine has been limited by its pharmacological characteristics. AREAS COVERED: This paper reviews the role of vincristine in the treatment of lymphoid malignancies. This review summarizes its efficacy and toxicity, and focuses on the pharmacokinetic features of vincristine that affect clinical outcomes. EXPERT OPINION: As a single agent, vincristine is associated with brief and incomplete responses, but in combination with other agents, vincristine has dramatically improved the outcomes of lymphoid malignancies such as ALL. Vincristine is a key drug of hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, an intensive chemotherapeutic regimen for the treatment of ALL, and of cyclophosphamid, adriamycin, vincristine and prednisone, which has been used extensively in the treatment of patients with aggressive or indolent lymphomas and Richter syndrome. The strong antileukemic activity of vincristine has been limited by its variable and unpredictable pharmacological characteristics, narrow therapeutic index and neurotoxicity profile. These characteristics prompted the development of liposomal vincristine, which has optimized its clinical application. Liposomal vincristine has promising antileukemic activity, and it is approved by the FDA as a single agent for the treatment of relapsed/refractory Philadelphia chromosome-negative ALL.