Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation

In an attempt to limit toxicities associated with dose-intensive therapy us ed for transplant regimens, we performed a pilot study using amifostine wit h high-dose busulfan (12 mg/kg), melphalan (100 mg/m(2)), and thiotepa (500 mg/m(2)) in 21 patients with a variety of malignancies. After 3 days of or al busulfan, amifostine was given at 910 mg/m(2) IV for 10 minutes, precedi ng the infusion of each of 2 doses of melphalan and thiotepa given for 4 da ys. Antiemetic premedication for amifostine was given to all patients. The median patient age was 50 years (range: 32-65 years). Twenty-one patients r eceived 82 separate amifostine infusions. One patient discontinued amifosti ne after the second dose because of severe nausea and emesis, and two infus ions were temporarily held secondary to hypotension. Of these 82 cycles, th ere was a total of 37 episodes of nausea/vomiting, 28 episodes of sneezing, 11 episodes of flushing, and 1 episode of oral paresthesia. Systolic blood pressure and mean arterial pressure decreased by a mean of 8.4 mm Hg and 5 .0 mm Hg, respectively. In general, the infusion was well tolerated. Patien ts were observed until discharge home (N = 15), until initiation of an addi tional tandem transplant procedure (N = 4), or until death (N = 2). All twe nty-one patients experienced nonhematologic toxicities grade II or greater. Grade II toxicities included mucositis (N = 21), gastrointestinal (N = 3), skin (N = 1), and liver (N = 1), and grade III toxicities included liver ( N = 1). Mucositis was also scored according to a detailed toxicity assessme nt. Mucositis did not appear to be improved with amifostine when compared w ith a control group of patients not receiving amifostine. Renal dysfunction after transplantation was decreased in the amifostine group, whereas there was no significant effect on posttransplant hepatic dysfunction. Although these data demonstrate the feasibility of delivering parenteral amifostine in conjunction with dose-intensive chemotherapy and autologous peripheral b lood stem cell transplantation, there was no evidence of a significant redu ction in nonmarrow toxicities.