Feasibility and Efficacy of Subcutaneous Amifostine Therapy in Patients With Head and Neck Cancer Treated With Curative Accelerated Concomitant-Boost Radiation Therapy

ArticleinArchives of Otolaryngology - Head and Neck Surgery 132(2):141-5 · March 2006with5 Reads
DOI: 10.1001/archotol.132.2.141 · Source: PubMed
Abstract
To assess the feasibility and efficacy of subcutaneous amifostine therapy in patients with head and neck cancer treated with curative accelerated radiotherapy (RT). Retrospective study. University of Lausanne, Lausanne, Switzerland. Thirty-three consecutive patients (male-female ratio, 4.5; median age, 54 years [age range, 39-76 years]). Between November 2000 and January 2003, the 33 patients were treated with curative definitive (n = 19) or postoperative (n = 14) RT with (n = 26) or without (n = 7) chemotherapy. All patients received conformal RT. Fractionation schedule consisted of concomitant-boost (Friday afternoon session) accelerated RT using 70 Gy (2 Gy per fraction) in 6 weeks in patients treated with definitive RT and 66 Gy (2 Gy per fraction) in 5 weeks and 3 days in the postoperative setting. Parotid glands received at least 50 Gy in all patients. Amifostine was administered to a total dose of 500 mg subcutaneously, 15 to 30 minutes before morning RT sessions. All patients received their planned treatment (including chemotherapy). Ten patients received the full schedule of amifostine (at least 25 injections), 9 received 20 to 24 doses, 4 received 10 to 19 doses, 5 received 5 to 9 doses, and 5 received fewer than 5 doses. Fifteen patients (45%) did not show any intolerance related to amifostine use. Amifostine therapy was discontinued because of nausea in 11 patients (33%) and hypotension in 6 patients (18%), and 1 patient refused treatment. No grade 3, amifostine-related, cutaneous toxic effects were observed. Radiotherapy-induced grade 3 acute toxic effects included mucositis in 14 patients (42%), erythema in 14 patients (42%), and dysphagia in 13 patients (39%). Late toxic effects included grade 2 or more xerostomia in 17 patients (51%) and fibrosis in 3 patients (9%). Grade 2 or more xerostomia was observed in 8 (42%) of 19 patients receiving 20 injections or more vs 9 (64%) of 14 patients receiving fewer than 20 injections (P = .15). Subcutaneous amifostine administration in combination with accelerated concomitant-boost RT with or without chemotherapy is feasible. The major adverse effect of subcutaneous administration was nausea despite prophylactic antiemetic medication, and hypotension was observed in only 6 patients (18%).
    • "The other three studies tested the feasibility of the use of subcutaneous amifostine [41, 43, 44]. One of them combined 26 patients who received chemoradiotherapy with seven patients, who received radiotherapy alone [41] . Treatmentrelated toxicity was described in all three studies, but due to the lack of control subjects, no conclusion on the effect of amifostine on oral mucositis could be drawn in either study. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. Results: Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. Conclusion: Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.
    Full-text · Article · Oct 2012
    • "A frequent documented major drawback of the use of amifostine is its severe adverse effects (e.g., hypotension, vomiting, nausea, allergic reaction), particularly when administered intravenously. Recent studies indicated that these adverse effects might be reduced by subcutaneous administration of amifostine because subcutaneous injection seems to be better tolerated by patients than intravenous administration [87, 88]. The main adverse effect after subcutaneous administration was nausea/vomiting, while more severe adverse effects such as hypotension and allergic reactions were not observed. "
    [Show abstract] [Hide abstract] ABSTRACT: Abstract PURPOSE: This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. RESULTS: The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. CONCLUSIONS: Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.
    Full-text · Article · Mar 2010
    • "A frequent documented major drawback of the use of amifostine is its severe adverse effects (e.g., hypotension, vomiting, nausea, allergic reaction), particularly when administered intravenously. Recent studies indicated that these adverse effects might be reduced by subcutaneous administration of amifostine because subcutaneous injection seems to be better tolerated by patients than intravenous administration [87, 88]. The main adverse effect after subcutaneous administration was nausea/vomiting, while more severe adverse effects such as hypotension and allergic reactions were not observed. "
    [Show abstract] [Hide abstract] ABSTRACT: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
    Full-text · Article · Mar 2010
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