Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation

Abstract

Summary:In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n ¼ 43) or not receive (n ¼ 47) amifostine 910 mg/m 2 prior to melphalan 200 mg/m 2 . Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65% of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P ¼ 0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P ¼ 0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14% of the amifostine and control groups, respectively (P ¼ 0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to highdose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis. Bone Marrow Transplantation (2005) 35, 971-977.

A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation

“…7,15 Amifostine, a thiol-based cytoprotective agent, has been shown to reduce mucositis associated with high-dose melphalan. 8 Amifostine-treated patients had a reduction in the overall incidence of mucositis and less frequent severe mucositis. There was not, however, any difference in the utilization of parenteral nutrition or narcotics for pain relief.…”

“…6 The only approved agent for prevention of mucositis associated with high-dose therapy is palifermin, but several studies have shown that low-energy lasers or amifostine can reduce the incidence and severity of mucositis. 7,8 Additionally, there have been several reports of reduced oral mucositis in patients who kept ice chips in their mouth during infusional chemotherapy. 9,10 The scientific rationale for this approach is that cryotherapy leads to vasoconstriction and decreased blood flow to the oral cavity, which reduces the exposure of the buccal mucosa to chemotherapy.…”

High-dose chemotherapy with autologous stem cell transplantation for multiple myeloma: what predicts the outcome? Experience from a developing country

“…Higher frequency of severe mucositis in our study may possibly be a result of multiple factors including poor oral hygiene, prior extensive chemotherapy (33 patients received more than one regimen and, consequently, higher doses of steroids) and presence of progressive disease, renal failure and paraparesis in some patients. We attempted use of amifostine in 16 patients prior to highdose melphalan as suggested by Spencer et al; 24 grade III and IV mucositis was 43.8 and 31.3% compared with 38.1 and 33.3%, P ¼ NS among patients who did not receive amifostine. Recently, use of keratinocyte growth factor (pelifermin) has been associated with a reduced risk of mucositis.…”

Autologous stem cell transplantation beyond 60 years of age

“…Recently, amifostine has been shown to reduce mucosal toxicity with associated complications in myeloma patients receiving high-dose MEL. 67,68 A human recombinant keratinocyte growth factor palifermin has reduced significantly the severity and duration of mucositis in patients with haematological malignancies receiving HDT. 69 Elderly patients receiving HDT might be optimal candidates for the use of these protective agents.…”