Approaches to managing carboplatin-induced thrombocytopenia: focus on the role of amifostine.

Thrombocytopenia is a significant problem for patients receiving prolonged or aggressive chemotherapy for malignancy. For carboplatin, it is the predominant dose-limiting toxicity and it is cumulative in nature. A number of agents have been evaluated for efficacy in reducing the problem of thrombocytopenia. Some have proved valueless and have been discarded. Others (eg, recombinant thrombopoietin) are under current study, and one (interleukin-11 or oprelvekin) is now commercially available. In addition, the currently available cytoprotectant, amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), has been shown to reduce the severity and duration of thrombocytopenia caused by carboplatin. Because of the short half-life of amifostine relative to that of carboplatin, multiple doses of amifostine have been administered in conjunction with carboplatin. The optimal dosing regimen with amifostine and carboplatin needs to be further evaluated in clinical studies. Future trials will also expand these observations to carboplatin-containing combination chemotherapy regimens and will further define the role of amifostine as a multilineage bone marrow protectant. The ability of amifostine to demonstrate multilineage bone marrow protection differentiates it from currently available growth factors and fulfills a medical need, including reducing the need for platelet transfusions and maintaining the desired chemotherapy dose intensity.