American Society of Clinical Oncology Clinical Practice Guidelinesfor the Use of Chemotherapy and Radiotherapy Protectants

Abstract

Mesna: (1) Mesna, dosed as detailed in these guidelines, 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 with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-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 and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives

“…The American Society Clinical Oncology Guidelines for the use of chemoprotectants does not support the routine use of amifostine [58]. At the time the guidelines were prepared, there were no data from phase II or III studies to evaluate whether amifostine protects against paclitaxel neurotoxicity.…”

“…The available clinical data were from a phase I doseescalation study of paclitaxel (3-hour infusion) and amifostine. Twenty-two patients with advanced malignancies were treated with 910 mg/m 2 of amifostine and escalating doses of paclitaxel starting at 135 mg/m 2 up to 310 mg/m 2 [58]. Higher doses of paclitaxel were reached when drug administration was preceded by amifostine.…”

Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma

“…9 Amifostine (WR-2721) is an organic thiophosphate compound which selectively protects normal tissue from the cytotoxic damage induced by anticancer agents. 10 The protective effect of amifostine was first demonstrated in cells exposed to radiation. 11 Interest in the potential value of amifostine in cancer therapeutics further increased when it was recognized in phase II and phase III clinical trials that amifostine also protected normal tissues, but not tumor cells against the toxic effects of several chemotherapeutic agents, [12][13][14][15][16][17][18][19] reducing the occurrence and severity of neutropenia and other non-hematological toxicities without affecting anti-cancer efficacy.…”

High-dose epirubicin, preceded by dexrazoxane, given in combination with paclitaxel plus filgrastim provides an effective mobilizing regimen to support three courses of high-dose dense chemotherapy in patients with high-risk stage II–IIIA breast cancer

“…Dexrazoxane protects against the cardiotoxicity of anthracyclines, at least in part, through the chelation of intracellular iron, which may decrease anthracyclineinduced free radical generation. 8 Dexrazoxane has also been reported to inhibit the catalytic activity of topoisomerase II and to potentiate the efficacy of a number of antitumor agents. 25,26 Recently, dexrazoxane has shown protection against anthracycline extravasation, but the precise mechanism was not defined.…”

“…7 Dexrazoxane is a derivative of EDTA that has been shown to decrease significantly the incidence of cardiomyopathy in patients treated with anthracyclines. 8 Results of a randomized trial demonstrated that dexrazoxane protects against the development of cardiotoxicity when high single doses of epirubicin are used, without affecting antitumor activity. 7 No data are available regarding the use of dexrazoxane in combination with high-dose anthracyclines, with or without other agents, for PBSC mobilization.…”