Vomiting associated with pentostatin and pentostatin plus alpha-interferon: unique pattern and potential mechanisms.

Abstract

Pentostatin (2'-deoxycoformycin) is a unique antineoplastic agent that has proven valuable in the treatment of a number of lymphoid malignancies. Dose-limiting toxicities observed in clinical trials include central nervous system (CNS) effects and acute renal failure. Information regarding the incidence, duration, and severity of nausea and vomiting from published reports is conflicting and insufficient to provide recommendations for optimal supportive measures. We report the results of a phase I study where pentostatin was associated with a 20% incidence of vomiting following courses one and two (pentostatin alone). The third course of pentostatin administered concurrently with alpha interferon resulted in a 29% incidence of vomiting and by course four had increased to 50%. Grade of severity was similarly increased, and nausea and vomiting was the dose-limiting toxicity in 6 of 15 patients. Forty-two percent of all episodes of vomiting were delayed in onset (onset 24 hr after drug administration) and in over 80% of cases persisted for greater than 48 hr in duration. Potential mechanisms that may account for these findings, as well as recommendations regarding antiemetic therapy are provided.