A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma

Bourhis, Jean; Crevoisier, R. de; Abdulkarim, Bassam; Deutsch, Éric; Lusinchi, A.; Luboinski, B.; Wibault, P.; Brizel, D.M.; Wasserman, Todd H.; Henke, Michael; Strnad, Vratislav; Rudat, Volkar; Monnier, Alain; Eschwège, F.; Zhang, J; Russell, Lisa M.; Oster, Wolfgang; Sauer, Rolf; Koukourakis, M.; Kyrias, G; Kakolyris, S; Kouroussis, Charalambos; Frangiadaki, Chryssi; Giatromanolaki, Alexandra; Retalis, G.; Georgoulias, Vassilis; Huang, Eric Yi-Hsiu; Leung, Sam; Wang, C.J; Chen, H.C; Sun, Li‐Min; Fang, Fu Min; Yeh, Shyh-An; Hsu, Heng-Wei; Hsiung, Ching-Yeh; Makkonen, Tanja; Minn, Heikki; Jekunen, Antti; Vilja, Pekka; Tuominen, Juhani; Joensuu, Heikki

doi:10.1016/s1278-3218(00)00074-3

Cited by 18 publications

(32 citation statements)

References 6 publications

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“…Studies evaluating the prophylactic use of amifostine during radiotherapy have uniformly reported a reduction of the incidence and severity of oral mucositis, but produced inconsistent results concerning the tolerability of the substanceregardless of its dosage and route of administration. [180][181][182] Similarly, three out of four studies have demonstrated mucosaprotective effects of amifostine during simultaneous radiochemotherapy. [183][184][185][186] Data on the use of amifostine in the prevention of chemotherapy-induced oral mucositis are scant, because the evaluation of mucositis does not constitute a primary endpoint of most studies.…”

Section: Amifostinementioning

confidence: 95%

“…A series of clinical trials have reported on mucosaprotective effects of subcutaneous dosages up to 500 mg and on intravenous use at doses up to 740 mg/m 2 . [180][181][182][183][184][185][186][187][188][189] Side effects, mostly nausea and hypotension, seem to be more pronounced at higher doses and upon intravenous use, whereas, the optimal mucosaprotectant dose and route of administration remains to be defined. Studies evaluating the prophylactic use of amifostine during radiotherapy have uniformly reported a reduction of the incidence and severity of oral mucositis, but produced inconsistent results concerning the tolerability of the substanceregardless of its dosage and route of administration.…”

Section: Amifostinementioning

confidence: 99%

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Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Köstler

Hejna

Wenzel

et al. 2001

CA: A Cancer Journal for Clinicians

285

252

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The incidence and severity of oral mucositis is influenced by the type of antineoplastic treatment administered and by patient-related factors. Severe courses of oral mucositis are observed during simultaneous radiochemotherapy, which Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and TreatmentWolfgang J. Köstler, MD; Michael Hejna, MD; Catharina Wenzel, MD; and Christoph C. Zielinski, MD 290 CA A Cancer Journal for Clinicians ABSTRACT Chemotherapy-and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses.The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. affects virtually all patients with head and neck cancer who receive this therapeutic modality. 8 However, up to 40% of patients treated with conventional chemotherapy and the more than 70% of patients undergoing conditioning therapy for bone marrow transplantation also experience oral treatment-related complications. 9,10The pathogenesis of oral mucositis is not fully understood, yet it is thought to involve direct and indirect mechanisms. Direct mucosal injury by radiation and chemotherapy interfere with the average 5-to 14-day turnover time of the oral epithelium 11 and induce apoptosis. Indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapyinduced neutropenia have been postulated to contribute to the development of oral mucositis and also promote the emergence of bacteria, fungi, and viruses on damaged mucosa.12 Although a linear relationship among the occurrence of oral mucositis, oral and systemic granulocyte counts, and a coincidence of resolution of mucositis with neutrophil recovery, has been demonstrated, 10,[13][14][15] significant mucositis can occur in the absence of myelotoxicity. 16,17 In addition, the prophylactic or therapeutic elimination of the pathogenic mucosal flora frequently observed in patients developing oral mucositis by various antiseptic and antimicrobial agents can at most alleviate the course of oral mucositis (see Antimicrobal Agents p. 302).Based upon these considerations, newer pathophysiologic concepts have emerged characterizing oral mucositis as having an initial inflammatory/vascular phase, an epithelial phase, a (pseudomembraneous) ulcerative/bacteriological phase and a healing phase.18 During the inflammatory phase, tissue injury induces release of free radicals, modified proteins and proinflammatory cytokines including interleukin-1β, prostaglandins and tumor necrosis factor-α (TNF-α) by epithelial, endothelial, and connective tissue cells. These ...

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Section: Amifostinementioning

confidence: 95%

Section: Amifostinementioning

confidence: 99%

Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Köstler

Hejna

Wenzel

et al. 2001

CA: A Cancer Journal for Clinicians

285

252

View full text Add to dashboard Cite

show abstract

“…With regard to oral mucositis, the literature is conflicting with some studies suggesting amifostine to be beneficial in prevention of oral mucositis [4,5,7,11,13,[16][17][18][19][20][21][22][23][24] and some studies suggesting that amifostine does not reduce mucositis prevalence or severity [6,8,10,[25][26][27][28][29][30][31]. Stokman et al performed a meta-analysis of seven studies and reported a positive preventive effect of amifostine on severe oral mucositis [32].…”

Section: Introductionmentioning

confidence: 99%

Systematic review of amifostine for the management of oral mucositis in cancer patients

Nicolatou‐Galitis

Sarri²,

Bowen

et al. 2012

Support Care Cancer

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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

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“…Several studies reported that the clinical outcome was not affected by amifostine. 33,38,39 In addition, the difference in overall survival rates in two studies was not significant between the groups. 14,35 In our study no significant difference was observed between the groups in terms of the median overall survival.…”

Section: Discussionmentioning

confidence: 82%

“…32 Bourhis et al reported that amifostine reduced the frequency of severe mucositis and the duration of mucositis induced by very accelerated RT; however, it was not well tolerated. 33 Ozsahin et al evaluated side effects in patients treated with amifostine during accelerated RT and reported that grade 3 dysphagia, grade 3 mucositis, and grade 3 erythema occurred in 39%, 42%, and 43% of the patients, respectively. In terms of late side effects, grade 3 xerostomia and grade 3 fibrosis occurred in 15% and 0% of the patients, respectively, but their study did not include a control group to compare the efficacy of amifostine.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

Demiroz¹,

Özkan²,

Cebelli³

et al. 2012

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : We aimed to investigate the effect of amifostine on acute and late side effects, and its tolerability in head and neck cancer patients treated with radiotherapy (RT). M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : The study included 87 patients with primary head and neck cancers and cervical lymph node metastases from unknown primary cancers treated with RT alone or combined with chemotherapy (CT). Forty-one patients (47%) received amifostine combined with RT (ART group) and 46 patients (52%) received RT without amifostine (RT group). The patients were evaluated every week during the treatment and at month 1 and 2 after the completion of RT for acute side effects and month 3, 6, 9, 12, and 24 after the treatment for late side effects according to SOMA/LENT scale. Amifostine was administered prior to RT, along with anti-emetic prophylaxis. The two groups were compared with the Student's t and MannWhitney U and Chi-square tests. R Re es su ul lt ts s: : The ART group had significantly less toxicity (grade 1 mucositis, grade 2 fibrosis) than patients in the RT group (p=0.001, p=0.03, respectively). At week 3 of RT grade 2 mucositis developed in two patients (5%) in the ART group and 10 patients (22%) in the RT group (p=0.02). The protective effect of amifostine on skin reactions developed at week 4 of RT (p=0.05). Grade 3 xerostomia at 9, 12, and 15 months of follow-up (p=0.02, p=0.02, and p=0.02, respectively), grade 2 xerostomia at 18 and 24 months (p=0.02 and p=0.01, respectively) and fibrosis at 15, 18 and 24 months (p=0.05, p=0.02 and p=0.02, respectively) decreased markedly in the ART group compared with the RT group. Emesis was the most common adverse effect of amifostine. C Co on nc cl lu us si io on n: : Daily administration of amifostine during RT was effective in avoiding late grade 2-3 xerostomia, as well as grade 2 fibrosis. K Ke ey y W Wo or rd ds s: : Radiotherapy; head and neck cancer; amifostine; xerostomia Ö ÖZ ZE ET T A Am ma aç ç: : Amifostinin radyoterapi (RT) ile tedavi edilmiş baş ve boyun kanseri hastalarında akut ve geç yan etkiler üzerindeki etkisini ve tolerabilitesini araştırmayı amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmaya, tek başına RT veya RT ve eş zamanlı kemoterapi (KT) ile tedavi edilmiş primer baş ve boyun kanseri olan ve primeri bilinmeyen bir kanserden servikal lenf düğümlerine metastaz yapmış 87 hasta dâhil edildi. Kırk bir hastaya (47%) RT ile birlikte amifostin (ART grup) ve 46 hastaya (52%) amifostin olmaksızın RT (RT grubu) verildi. Olgular, tedavi sırasında akut yan etkiler açısından her hafta ve RT bittikten sonra 1. ve 2. ayda, geç yan etkiler açısından ise tedavi bittikten sonra 3., 6., 9., 12., ve 24. aylarda SOMA/LENT skalasına göre değerlendirildiler. Amifostin RT'den önce antiemetik profilaksi ile beraber uygulandı. İki grubun, komplikasyonlar üzerindeki etki açısından karşılaştırılmasında Student-t ve Mann Whitney-u testleri kullanıldı. B Bu ul lg gu ul la ar r: : AR...

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A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma

Cited by 18 publications

References 6 publications

Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Systematic review of amifostine for the management of oral mucositis in cancer patients

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

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