Postradiotherapy quality of life for head-and-neck cancer patients is independent of xerostomia

PURPOSE: To determine the relationship between quality of life (QOL) and xerostomia over time for patients undergoing radiotherapy (RT) for head-and-neck cancer in a prospective clinical trial. METHODS AND MATERIALS: Patients with head-and-neck cancer were randomized to pilocarpine (n = 65) vs. placebo (n = 65) during RT. QOL was measured using the McMaster Head and Neck Radiotherapy Questionnaire (HNRQ). Xerostomia was measured on a linear analog scale. No statistically significant differences were observed between arms; all 130 patients were analyzed together. RESULTS: Baseline QOL data were obtained for 98.5% of participants. The baseline HNRQ score of 5.7 declined significantly to 4.0 (p <0.0001) by RT Week 6 and returned to baseline (5.8) by 6 months after treatment. This represents a large, clinically important change of 1.7 of 7 (24%; effect size 1.34). The decline in HNRQ score during RT paralleled the onset of xerostomia on the linear analog scale (r = 0.36 at 1 month). After treatment, the QOL scores recovered without improvement in xerostomia. The trajectory of the linear analog scale score resembled that of the HNRQ's single xerostomia question (r = 0.75 at 1 month). CONCLUSION: Quality of life recovers to baseline after RT, despite persistent xerostomia. Either a response shift occurs or xerostomia in the absence of acute mucositis has a relatively small influence on overall QOL.     

Effect of Cepharanthin to prevent radiation induced xerostomia in head and neck cancer

We retrospectively examined the effect of Cepharanthin to prevent radiation xerostomia in 37 cases of head and neck cancer. In the Cepharanthin group, the degree of xerostomia was milder than in the non-Cepharanthin group in spite of higher normal tissue complication probability (NTCP) and mean dose (MD) of parotid glands. In the non-Cepharanthin group, the degree of xerostomia was significantly correlated with NTCP and MD of parotid glands. MD of parotid glands and use of Cepharanthin were significantly related to more severe xerostomia by multivariate analysis with logistic regression. Cepharanthin may prevent radiation xerostomia after radiotherapy for head and neck cancer.     

A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

PURPOSE: Intravenous amifostine 200 mg/m2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. PATIENTS AND METHODS: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of > or =Grade 2 acute xerostomia. RESULTS: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of > or =Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of > or =Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. CONCLUSIONS: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.     

Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer

PURPOSE: To assess observer-based vs. patient self-reported scoring of xerostomia after intensity-modulated radiotherapy (IMRT) of head-and-neck (HN) cancer. METHODS: A total of 38 patients who had received IMRT for HN cancer underwent xerostomia evaluations 6 to 24 months after completion of therapy using three methods each time: (1) Grading by 3 observers according to the Radiotherapy Oncology Group/European Organization for Research and Therapy of Cancer (RTOG/EORTC) system; (2) patient self-reported validated xerostomia questionnaire (XQ); and (3) major salivary gland flow measurements. RESULTS: The interobserver agreement regarding the RTOG/EORTC grades was moderate: kappa-coefficient 0.54 (95% CI=0.31-0.76). The correlations between the average RTOG/EORTC grades and the salivary flow rates were not statistically significant. A trend for significant correlation was observed between these grades and the percent (relative to the pretherapy) nonstimulated salivary flow rates (p=0.07), but not with the percent stimulated flow rates. Better correlations were found between grading made more than the median time (15 min) after the last liquid sipping and the nonstimulated (but not the stimulated) flows compared with grading made shortly after sipping. In contrast, significant correlations were found between the XQ scores and the nonstimulated (p<0.005) and the stimulated (p<0.005) salivary flow rates, as well as with the percentages of the corresponding pretherapy values (p=0.002 and 0.038, respectively). No significant correlation was found between the RTOG/EORTC grades and the XQ scores. The observer-based grades underestimated the severity of xerostomia compared with the patient self-reported scores. CONCLUSIONS: Patient self-reported, rather than physician-assessed scores, should be the main end points in evaluating xerostomia.     

Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.     

Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms

PURPOSE: In a single-institution, double-blind, prospective, randomized trial, we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head-and-neck cancer patients. METHODS AND MATERIALS: We randomized 58 head-and-neck cancer patients between oral aloe vera and placebo. To be included in this Phase II protocol, patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002. We examined patients biweekly for mucositis at 15 head-and-neck subsites and administered quality-of-life questionnaires. RESULTS: Patients in the aloe and placebo groups were statistically identical in baseline characteristics. By the end of treatment, the two groups were also statistically identical in maximal grade of toxicity, duration of Grade 2 or worse mucositis, quality-of-life scores, percentage of weight loss, use of pain medications, hydration requirement, oral infections, and prolonged radiation breaks. CONCLUSION: In our randomized study, oral aloe vera was not a beneficial adjunct to head-and-neck radiotherapy. The mean quality-of-life scores were greater in the aloe vera group, but the differences were not statistically significant. Oral aloe vera did not improve tolerance to head-and-neck radiotherapy, decrease mucositis, reduce soreness, or otherwise improve patient well-being.     

Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study

PURPOSE: Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer. METHODS AND MATERIALS: Patients from European and American study centers received i.v. amifostine 300 mg/m2 (n = 67) or placebo (n = 65) before carboplatin 70 mg/m2 and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m2 or placebo before radiotherapy on other days. RESULTS: Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments. CONCLUSIONS: The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.     

Effect of prophylactic fluconazole on oral mucositis and candidiasis during radiation therapy for head-and-neck cancer

PurposeRadiation therapy (RT) or chemoradiation therapy (CRT) for carcinoma of the head and neck can result in high rates of candidiasis and mucositis. Prophylactic fluconazole (FCZ) has been shown to reduce the incidence of candidiasis. We report our outcomes of patients with head-and-neck cancer undergoing CRT treated prophylactically with FCZ.Methods and MaterialsAn institutional review board-approved database of head-and-neck cancer patients treated with RT or CRT was reviewed to identify patients treated between 2004 and 2009 who received at least 50 Gy to approximately two-thirds of the oral cavity or oropharynx mucosa. Eligible patients were divided into 2 groups: the usual care group and the prophylaxis group. The primary endpoints were the incidence of mucositis and candidiasis.ResultsA total of 181 patients were eligible for analysis: 72 patients in the prophylactic group and 109 patients in the usual care group. Patient characteristics and radiation dose were comparable between groups. RT alone was given in 28 patients (16%). Mucositis data were available in 161 (89%) patients. Grade 2 or higher mucositis was seen in 131 (81%) patients. Prophylactic FCZ had significantly decreased grade 2 or higher mucositis. In the usual care group and prophylaxis group patients, 83 of 93 patients (89.3%) and 48 of 68 patients (70.6%), respectively, developed grade 2 or higher mucositis (P = .003).ConclusionsProphylactic administration of FCZ twice weekly during CRT for head-and-neck cancer reduces incidence of mucositis and thrush.     

Pilot study of postoperative reirradiation, chemotherapy, and amifostine after surgical salvage for recurrent head-and-neck cancer

PURPOSE: Salvage surgery alone after radiotherapy (RT) failure for locally advanced head-and-neck cancer is frequently unsuccessful because of subsequent recurrence. We designed a prospective protocol to determine the feasibility, toxicity, and preliminary efficacy of a regimen of postoperative reirradiation, chemotherapy and the radioprotector amifostine after salvage head-and-neck surgery. METHODS AND MATERIALS: Eligible patients had biopsy-proven locally advanced, but resectable, recurrence without distant metastases >6 months after previous RT. After adequate healing from surgery, patients underwent RT to 54-66 Gy within 5-5.5 weeks to the resection bed (lifetime RT dose, 100-130 Gy). The fractionation was 1.5 Gy b.i.d. within 2 weeks, followed by a 1-week break, followed by 1.5 Gy b.i.d. to a total of 54-66 Gy. Chemotherapy consisted of cisplatin 25 mg/m(2)/d three times and 5-fluorouracil 500 mg/m(2)/d continuous infusion for 4 days, for two cycles (Weeks 1 and 5). Amifostine (500 mg i.v.) was administered daily, 30 min before either the morning or the afternoon RT. RESULTS: Between 1998 and 2001, 16 patients were enrolled and studied. Two patients had gross residual disease after surgery; all other patients underwent complete surgical resection but had high-risk features (rT3-T4 and/or N+ disease). Three patients (19%) had serious acute toxicity events (nonneutropenic infections) that were reversible. The median follow-up was 35 months. The actuarial locoregional control rate was 81% at 3 years. Three patients developed isolated distant metastases and one developed a fatal second primary cancer (hepatoma). The 2- and 3-year actuarial event-free survival rate was 81% and 50%, respectively. The 2- and 3-year actuarial overall survival rate was 81% and 63%, respectively. Both patients who had gross residual disease after surgery had early recurrence; if these patients were excluded from analysis, the 3-year actuarial survival and event-free survival rate was 67% and 59%, respectively. Of the 16 patients, 6 (38%) developed Grade 3+ late toxicity, including one fatal stroke and two life-threatening major vessel necrosis and/or bleeding events. CONCLUSION: This regimen of postoperative reirradiation/chemotherapy plus amifostine is feasible and was well tolerated acutely, with encouraging oncologic efficacy. However, the incidence and severity of late effects was significant and suggests that modifications are necessary for future studies in this patient population.     

中药防治鼻咽癌综合治疗中口咽急性毒性的临床研究

背景与目的:口咽炎是鼻咽癌放射治疗中最常见的非血液学急性毒性,在肿瘤晚期患者的放化综合治疗中尤为严重,并可能影响治疗结果。本研究拟探讨中药配合鼻咽癌放化综合治疗,以防治口咽急性毒性的疗效。方法:选择101例临床分期为Ⅲ～Ⅳa期的鼻咽癌患者随机分为实验组(配合中药)52例,对照组(使用朵贝氏液)49例。两组患者鼻咽平均放疗剂量为:实验组(70.31±1.21)Gy,对照组(70.78±1.95)Gy。化疗采用同期放化疗方法:DDP30mg/cm2,每周1次,放疗第1至6周,共6次。从放疗开始至结束,实验组服中药每日一剂,分5至8次含服;对照组每日用朵贝氏液含漱5～8次。观察指标:口咽和血液急性毒性分级、放疗疗程总时间以及近期疗效。结果:(1)口咽毒性:实验组和对照组均无0级口咽急性毒性,Ⅰ～Ⅳ级急性毒性分别为Ⅰ级29例(55.77%)和2例(4.08%),Ⅱ级18例(34.62%)和17例(30.69%),Ⅲ级5例(9.62%)和22例(44.89%),Ⅳ级0例(0%)和8例(16.33%),两组比较有显著性差异(P=0.000);(2)血液学急性毒性:两组病例均无Ⅳ级血液学毒性发生,其中两组白细胞急性毒性比较(Z=-0.604,P=0.546),两组中性粒细胞急性毒性比较(Z=-0.226,P=0.821),两组血小板急性毒性比较(Z=-0.099,P=0.922),治疗过程中两组患者血液学急性毒性相似(P>0.05);(3)放疗疗程:实验组     

A Phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy

PURPOSE: Recent studies have suggested that acupuncture may improve radiation-induced xerostomia with an increase in the median salivary flow rate and sustained symptom relief. An acupuncture-like transcutaneous nerve stimulation method (Codetron) without invasive needles was developed to mimic acupuncture treatment. This Phase I-II study examined the effectiveness of Codetron in treating radiation-induced xerostomia. METHODS AND MATERIALS: Patients with symptomatic xerostomia after radical radiotherapy for head-and-neck cancer but with evidence of residual salivary function were recruited into the study. Two 6-week courses of Codetron treatment of acupuncture points preselected according to traditional Chinese medicine principles were given with a 2-week break between each course. Basal and citric acid-primed whole saliva production were measured at baseline and up to 1 year after treatment completion. Xerostomia symptoms were assessed by a five-item xerostomia symptom questionnaire with a visual analog scale and quality of life was evaluated using the Head and Neck Radiotherapy Questionnaire. RESULTS: We enrolled 46 patients in the study. All patients had received radiotherapy doses of >or=50 Gy to bilateral head-and-neck fields, including the parotid glands. Of the 46 patients, 37 completed the follow-up assessments at 3 and 6 months after treatment completion. No Codetron treatment-related complications occurred. Improvement in xerostomia symptoms was noted, with a mean increase in the visual analog scale score of 86 (p < 0.0005) and 77 (p < 0.0001) at 3 and 6 months after treatment completion, respectively. For all patients, the increase in the mean basal and citric acid-primed whole saliva production at 3 and 6 months after treatment completion was also statistically significant (p < 0.001 and p < 0.0001, respectively). No statistically significant change in the quality-of-life evaluation compared with baseline was observed. CONCLUSION: The results suggest that Codetron treatment improves whole saliva production and related symptoms in patients with radiation-induced xerostomia. The treatment effects were sustained for at least 6 months after Codetron treatment completion. A prospective randomized Phase III trial with appropriate controls is being planned.     

Investigation of how to prevent mucositis induced by chemoradiotherapy

Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using PA solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3. 0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44 ± 8. 0 days for the R solution group, 52 ± 18. 8 days for the P-A solution group, and 61 ± 19. 5 days for the S solution group, indicating that the R solution group significantly shortened the length of hospital stay compared to the S solution group. These results suggested that the use of an R or P-A solution may be effective in preventing oral mucositis and impaired nutrition of those undergoing chemoradiotherapy for head and neck cancer.     

Cytoprotective effect of amifostine in radiation-induced acute mucositis - a retrospective analysis

PURPOSE: To study the cytoprotective impact of amifostine against acute radiation mucositis. PATIENTS AND METHODS: A total of 117 cancer patients with carcinomas localized in pelvic organs, lung and head and neck were entered into this study. In a retrospective way, and in order to minimize the bias related to the investigator, 138 patients as historical controls were randomly selected from a database in our hospital. Acute radiation-induced gastrointestinal mucositis, esophagitis and stomatitis were assessed using the common toxicity criteria scale. The most severe grade recorded was evaluated as the final morbidity score for this patient. Mean toxicity score (MTS) was the mean value of recorded acute radiation toxicity. Mean interruption time (MIT) was the mean value of recorded interruption time due to radiation toxicity. RESULTS: A significantly reduced severity of symptomatology related to oral, esophageal and rectal mucosa was noted in the amifostine group (group A) (p < 0.05, chi-square test). Furthermore, a significant reduction of MTS as well as MIT was observed in group A versus the historical controls (group B) (p < 0.05, Mann-Whitney U test). CONCLUSION: The administration of amifostine seems to protect patients against radiation-induced mucositis, but further investigation with randomized trials is needed.     

Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer

PURPOSE: We performed this double-blinded, placebo-controlled study to determine the safety and efficacy of L-alanyl-L-glutamine in the prevention of mucositis in patients with head-and-neck cancer. METHODS AND MATERIALS: Thirty-two patients with head-and-neck cancer were treated with chemoradiotherapy (CRT) (radiotherapy daily up to 70 Gy plus cisplatin/5-fluoruracil once a week) and were asked to participate. Twenty-nine patients received the CRT schedule and were double-blindly assigned to receive either intravenous L-alanyl-L-glutamine 0.4 g/kg weight/day or an equal volume of saline (placebo) during chemotherapy days. RESULTS: Fourteen patients received L-alanyl-L-glutamine and 15 received placebo. Mucositis was assessed by the Objective Mucositis Score (OMS) and the World Health Organization (WHO) grading system. There was a significant difference in incidence of mucositis developed in patients receiving placebo compared with those who received L-alanyl-L-glutamine (p = 0.035). The number of patients with severe objective mucositis (OMS >1.49) was higher in the placebo group compared with the L-alanyl-L-glutamine group (67% vs. 14%, p = 0.007). L-alanyl-L-glutamine patients experienced less pain (three highest Numeric Rating Scale scores of 1.3/10 vs. 6.3/10 respectively, p = 0.008) and need for feeding tubes (14% vs. 60% respectively, p = 0.020) compared with placebo patients. No adverse effects related to the drug or the infusions were noted in either group. CONCLUSION: For patients with head-and-neck cancer receiving CRT, intravenous L-alanyl-L-glutamine may be an effective preventive measure to decrease the severity of mucositis.     

Matched case-control study of quality of life and xerostomia after intensity-modulated radiotherapy or standard radiotherapy for head-and-neck cancer: initial report

PURPOSE: To compare quality of life (QOL) and xerostomia between head-and-neck cancer patients who received standard radiotherapy (RT) and patients matched by factors known to affect QOL who received intensity-modulated RT (IMRT). METHODS AND MATERIALS: This was a prospective, longitudinal study of patients with head-and-neck cancer requiring bilateral neck irradiation who received IMRT at the University of Michigan and patients who received standard RT at affiliated clinics. Each patient received a validated head-and-neck cancer-related QOL questionnaire (HNQOL) consisting of four multi-item domains--Eating, Communication, Pain, and Emotion--and a validated patient-reported xerostomia questionnaire (XQ). In both questionnaires, the answers were scored 0-100, with higher scores denoting worse QOL or xerostomia. The questionnaires were given before therapy and at 1, 3, 6, 12, 18, and 24 months after the completion of therapy. Each standard RT patient was matched with several IMRT patients according to tumor site, stage, RT status (postoperative or definitive), and age. A linear mixed-effects model was fit to compare outcomes between the two treatment groups and to model trends over time. To account for matching, the differences in scores between the matched sets of patients were fit as a random intercept. Also, matching was taken into account in the model by using the standard error of the within-paired-groups differences. RESULTS: Between 1997 and 2002, 10 patients who had received standard RT and answered the XQ and HNQOL through at least 1 year were included in the study. Each of these patients was matched with a subgroup of 2-5 patients (median, 3) who had received IMRT, had similar patient and tumor characteristics, and answered the same questionnaires. A total of 30 patients were included in the IMRT group. During the initial months after therapy, the XQ and HNQOL summary scores worsened significantly in both groups compared with the pretherapy scores. Starting at 6 months, improvements of both XQ and HNQOL scores were found over time in the IMRT patients (p = 0.01 and 0.04, respectively), compared with no trend of improvement in the standard RT patients (p = 0.5 and 0.9, respectively). The trend of improvement over time in QOL in the IMRT patients was noted in most of the HNQOL domains (Eating: p = 0.07, Pain: p = 0.05, Emotion: p = 0.04, and Communication: p = 0.13), compared with no trend of improvement in most of the domains in the standard RT patients. As the scores of the IMRT (but not the standard RT) patients improved over time, the differences between the groups in the mean XQ and HNQOL summary scores widened. At 12 months, median XQ and HNQOL scores were lower (better) in the IMRT compared with the standard RT patients by 19 and 20 points, respectively, adjusted for the pretherapy values (p = 0.2). In both groups, the pretherapy XQ and HNQOL summary scores were significantly related to the respective posttherapy scores (p = 0.02 and p < 0.01, respectively). CONCLUSIONS: After initial posttherapy declines in both groups, xerostomia and QOL improved over time after IMRT but not after standard RT. The potential benefits gained from IMRT in xerostomia or in QOL, compared with standard RT, are best reflected late (> or = 6 months) after therapy.     

Subcutaneous administration of amifostine (ethyol) is equivalent to intravenous administration in a rat mucositis model

PURPOSE: Amifostine (Ethyol) is currently approved for intravenous (IV) administration to prevent xerostomia in patients receiving radiotherapy for head-and-neck cancer. Recently, subcutaneous (SC) administration has been explored as an alternative route. To determine whether SC administration was equivalent to IV administration, we used models to follow pharmacokinetics and oral mucosal protection in rats. METHODS: Amifostine was administered to rats at doses of 200, 100, or 50 mg/kg (1300, 650, or 325 mg/m(2)) IV or SC at various times before radiation at 15.3 Gy (protection studies) or harvest of blood and tissues for analysis by HPLC (pharmacokinetic studies). RESULTS: Amifostine administered IV or SC 1 h before radiation protected rats from mucositis, but the protective effect was more prolonged when amifostine was administered SC. Tissue levels of the active metabolite (WR-1065) were equivalent after SC administration. The correlation between tissue levels of WR-1065 and protection was strong, but that between blood levels of WR-1065 and protection was only weak. CONCLUSION: These data demonstrate that, in a rat model, SC administration of amifostine was at least as effective as that by IV.