American Society of Clinical Oncology clinical practice guidelines for theuse of chemotherapy and radiotherapy protectants

Purpose: Because toxicities associated with chemotherapy and radiotherapy c an adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radioth erapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food a nd Drug administration-approved agents that have potential chemotherapy- an d radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and q uestions about the role of these protectant agents in cancer care led to co ncern about the appropriate use of these agents. The American Society of Cl inical Oncology sought to establish evidence based, clinical practice guide lines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. Methods: A multidisciplinary Expert Panel reviewed the clinical data regard ing the activity of dexrazoxane, mesna, and amifostine. A computerized lite rature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speakin g literature ham June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed ta the entire Panel for review. Guidelines for use, revels of evidence, and grade s of recommendation were reviewed and approved by the Panel. Outcomes consi dered in evaluating the benefit of a chemotherapy- or radiotherapy-protecta nt agent included amelioration of short and long-term chemotherapy- or radi otherapy-related toxicities, risk of tumor protection by the agent, toxicit y of the protectant agent itself, quality of rife, and economic impact. To the extent that these data were available, the Panel placed the greatest va lue on lesser toxicity that did not carry a concomitant risk of tumor prote ction. Results and Conclusion: Mesna: (1) Mesna, dosed as detailed in these guidel ines, is recommended to decrease the incidence of standard-dose ifosfamide- associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity wi th ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced sa line diuresis is recommended to decrease the incidence of urothelial toxici ty associated with high dose cyclophosphamide use in the stem-cell transpla ntation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely r ecommended for patients with metastatic breast cancer who receive initial d oxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting a nd who may benefit from continued doxorubicin-containing therapy. (3) The u se of dexrazoxane in the adjuvant setting is not recommended outside of a c linical trial. (4) The use of dexrazoxane can be considered in adult patien ts who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors of her than breast cancer, although caution should be used in setti ngs in which doxorubicin-based therapy has been shown to improve survival b ecause of concerns of tumor protection by dexrazoxane. (5) There is insuffi cient evidence to make a guideline for the use of dexrazoxane in the treatm ent of pediatric malignancies, with epirubicin-based regimens, or with high -dose anthracycline-containing regimens. Similarly there is insufficient ev idence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients recei ving dexrazoxane should continue to be monitored for cardiac toxicity. Amif ostine: (1) Amifostine may be considered for the reduction of nephrotoxicit y in patients receiving cisplatin-based chemotherapy. (2) Although amifosti ne may be considered for the reduction of neutropenia in patients receiving alkylating agents, chemotherapy dose reduction or growth factor use should be considered err an alternative to the use of amifostine. (3) Present dat a are insufficient to recommend the use of amifostine for protection agains t thrombocytopenia or the routine use of amifostine to prevent cisplatin-as sociated neurotoxicity or ototoxicity. Similarly, present data are insuffic ient to support the use of amifostine for the prevention of paclitaxel-asso ciated neurotoxicity. (4) Use of amifostine may be considered to decrease t he incidence of acute and late xerostomia in certain patients undergoing fr actionated radiation therapy in the head and neck region, although present data ore insufficient to recommend the use of amifostine to prevent radiati on therapy-associated mucositis, Details regarding dose and management of a mifostine side effects, including hypotension, are included in the guidelin es. Further research is warranted to further define the Kits of these chemo therapy- and radiotherapy-protectant agents in the care of cancer patients. (C) 1999 by American Society of Clinical Oncology.