Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study.

Abstract

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0. 04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

• Authors: C A De Souza, G Santini, G Marino, S Nati, A M Congiu, A C Vigorito, E Damasio
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 33 Issue 7 Pg. 791-8 (Jul 2000) ISSN: 0100-879X [Print] Brazil
• PMID: 10881054 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Radiation-Protective Agents
• Cyclophosphamide
• Amifostine

Topics

• Adolescent
• Adult
• Amifostine (adverse effects, pharmacology)
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Cytoprotection (drug effects)
• Feasibility Studies
• Female
• Humans
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Radiation-Protective Agents (adverse effects, therapeutic use)
• Statistics, Nonparametric
• Treatment Outcome