Dosing considerations with amifostine: a review of the literature and clinical experience.

Numerous dosing regimens have been used in the clinical development of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA). Whereas the current recommended dose of amifostine is 910 mg/m2 administered intravenously as a 15-minute infusion 30 minutes before chemotherapy, other studies have demonstrated cytoprotection with lower doses, suggesting that the optimal biologic dose may indeed be lower. Amifostine doses that protect against the toxicities associated with daily fractionated radiotherapy are also lower, with a dose range of 200 to 340 mg/m2 per fraction commonly reported in the literature. The toxicities most commonly associated with amifostine, namely, hypotension and nausea and vomiting, are dose related. They can be reduced using adequate prophylactic measures and can be effectively managed if they occur. Hypocalcemia and allergic reactions also can be lessened or averted with precautionary measures. Thus, although amifostine is generally well tolerated at the current recommended doses, clinical studies of variations in the approved dosing regimen would be useful in further defining the optimal amifostine dose for chemoprotection, for radioprotection, and for inducing hematopoiesis in patients with refractory myelodysplastic syndromes.

Amifostine: drug profile and nursing implications of the first pancytoprotectant.

PURPOSE/OBJECTIVES: To review the drug profile and nursing implications of amifostine, a new cytoprotective agent. DATA SOURCES: Published articles, abstracts, professional communications, drug manufacturer, and personal experience with amifostine clinical studies. DATA SYNTHESIS: Amifostine increases the selectivity of specific anticancer agents for neoplastic cells by protecting normal tissue. It is indicated for reduction of the cumulative renal toxicity associated with repeated administration of cisplatin, in radiation therapy, and in several types of chemotherapies in patients with a variety of malignancies. Studies of amifostine used as a radioprotective and cytotoxic chemoprotective agent have demonstrated results against nephrotoxicity, neurotoxicity, hematotoxicity (granulocytopenia, leukopenia, and thrombocytopenia), and ototoxicity without adversely affecting tumor response or patient survival. The most common side effects are hypotension, nausea and vomiting (which may be severe), and a decrease in serum calcium concentrations. CONCLUSIONS: Amifostine is a new cytoprotectant, the first such agent with pancytoprotection. With appropriate management and premedication, amifostine is generally well-tolerated. Side effects are reversible following treatment discontinuation. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to be knowledgeable about cytoprotectants, a new class of drugs, in order to teach patients and their families about the need for cytoprotection so they can comply with and participate in treatment plans and to identify the need for and management of amifostine administration. Patient-care concerns include the risk of decreased systolic blood pressure that requires fluid infusion and postural management and potentially severe nausea and vomiting.

Psychological evaluation and preparation of the patient and family.

The suspected and confirmed diagnosis of cancer places stress on the patient and the family. In addition to the feelings of helplessness, guilt, frustration, alienation, and vulnerability that a diagnosis of cancer provokes, the diagnosis of gynecologic cancer can exacerbate these feelings due to its relationship to the perceived physiologic core of femininity, sexuality, and motherhood. Evaluation of the patient's existing coping skills, perceived seriousness of the illness, anticipated loss of control over physical functioning, and available family support is an essential part of the treatment plan. Preparing the patient and family for diagnosis and treatment is enhanced by supportive intervention techniques such as provision of accurate information, exploration of the patient's fears and fantasies, restoration of degrees of control in the patient's life, and exposure to peer support groups.