ERGO2: A Prospective, Randomized Trial of Calorie-Restricted Ketogenic Diet and Fasting in Addition to Reirradiation for Malignant Glioma.

PURPOSE: ERGO2 is the first randomized clinical trial on a calorically restricted ketogenic diet (KD) and intermittent fasting (KD-IF) in addition to reirradiation for recurrent malignant gliomas. METHODS AND MATERIALS: Fifty patients were randomized 1:1 to reirradiation combined with either a calorically unrestricted diet or KD-IF. The KD-IF schedule included 3 days of KD (21-23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. Primary endpoint was progression-free survival (PFS) at 6 months (PFS6). Secondary endpoints were PFS, local PFS, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. RESULTS: Four patients quit the trial before treatment and 3 patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6 and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1 ± 1.8 kg. No severe adverse events attributable to the diet occurred. PFS6 was not significantly different between the 2 groups (KD-IF: 20%; calorically unrestricted diet: 16%). Similarly, no difference in PFS, local PFS6, or OS was observable. Explorative analysis revealed that patients in the KD-IF group who had a glucose level of less than the median (83.5 mg/dL) on day 6 had significantly longer PFS and OS compared with those above the median (P < .05). CONCLUSIONS: KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioma. However, the short schedule reported here failed to increase the efficacy of reirradiation. CLINICALTRIALS. GOV NUMBER: NCT01754350.

Multicenter, phase III trial comparing selenium supplementation with observation in gynecologic radiation oncology: follow-up analysis of the survival data 6 years after cessation of randomization.

PURPOSE: In 2010, we reported that selenium (Se) supplementation during radiation therapy (RT) is effective for increasing blood Se levels in Se-deficient cervical and uterine cancer patients, and reduced the number of episodes and severity of RT-induced diarrhea. In the current study, we examine whether of Se supplementation during adjuvant RT affects long-term survival of these patients. PATIENTS AND METHODS: Former patients were identified and questioned with respect to their health and well-being. RESULTS: A total of 81 patients were randomized in the initial supplementation study, 39 of whom received Se (selenium group, SeG) and 42 of whom served as controls (control group, CG). When former patients were reidentified after a median follow-up of 70 months (range = 0-136), the actuarial 10-year disease-free survival rate in the SeG was 80.1% compared to 83.2% in the CG (P = .65), and the actuarial 10-year overall survival rate of patients in the SeG was 55.3% compared to 42.7% in the CG (P = .09). CONCLUSIONS: Our extended follow-up analysis demonstrates that Se supplementation had no influence on the effectiveness of the anticancer irradiation therapy and did not negatively affect patients' long-term survival. In view of its positive effects on RT-induced diarrhea, we consider Se supplementation to be a meaningful and beneficial adjuvant treatment in Se-deficient cervical and uterine cancer patients while undergoing pelvic radiation therapy.

Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology--a subgroup analysis of a multicenter, phase III trial.

BACKGROUND: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail. METHODS: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 µg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure. RESULTS: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916-4608). With a PTV of <= 1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50). In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046). CONCLUSIONS: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml).

Nutritional parameters for patients with head and neck cancer.

AIM: Determination of the optimal nutritional parameter to provide useful information for the individual patient and assessing the impact of nutritional status have on the prognosis of head and neck cancer. PATIENTS AND METHODS: Firstly a retrospective study analysed the outcome of 110 patients in relation to initial weight loss and weight loss at the end of radiotherapy. A second study investigated the changing bioimpedance (BIA) data of 27 survivors and 39 patients who died between their first and last measurement during nutritional therapy (at least four weeks). RESULTS: A critical initial weight loss is 10 kg or more at the point of diagnosis. At the end of radiotherapy the body mass reduction should be less than 15 kg. Raw data of BIA reflect the changing nutritional status at the end of life. We observed a stabilized phase angle in survivors (4.7° to 5.2°) whereas patients who died exhibited a significant lower phase angle (4.6° to 3.7°, p<0.05). CONCLUSION: The prognosis of head and neck cancer patients is highly related to their nutritional status. Specific nutritional anamnesis (initial weight loss, total weight loss, body mass index) and additional biophysical measurements such as BIA are recommended to monitor the individual status during the follow-up.

Selenium substitution during radiotherapy of solid tumours - laboratory data from two observation studies in gynaecological and head and neck cancer patients.

OBJECTIVE: Selenium is an essential cofactor of the enzyme glutathione peroxidase (GSH-Px), which is important for the endogenous detoxification of free radicals. A reduced activity of GSH-Px is related to increased toxicities due to radiation therapy during primary cancer treatment. Therefore, selenium substitution may be a new supportive strategy to diminish radiation-associated side effects. PATIENTS AND METHODS: The selenium blood concentrations of 121 radiotherapy patients were measured in two randomized observation studies (81 gynaecological tumours, 40 head and neck tumours). Measurements (atom absorption spectrometry) were performed on serum and whole blood (WB) samples before, in the middle of, at the end, and 6 weeks after radiotherapy. In cases of decreased selenium levels in WB, 63 patients (mean age 63.83+/-9.23 a) received selenium substitution (500 microg sodium selenite at RT days, 300 microg at the weekend) and 64 patients (mean age 63.03+/-10.47 years) were evaluated as control group without any selenium substitution. Both groups were well balanced according to tumour localization and stage. Reference values were 85-162 microg/l WB-selenium, and 65-135 microg/l serum-selenium. RESULTS: We measured the following WB selenium (Se) levels (Se-group vs. control group, U-test): begin RT 64.17+/-13.98 microg/l vs. 64.50+/-14.47 microg/l (p=0.869); mid RT 92.48+/-26.68 microg/l vs. 65.80+/-18.04 microg/l (p<0.001); end RT 93.78+/-25.90 microg/l vs. 64.06+/-17.54 microg/l (p<0.001); 6 weeks after RT 74.01+/-20.06 microg/l vs. 69.66+/-17.83 microg/l (p=0.183). The serum levels were as follows: begin RT 59.18+/-13.49 microg/l vs. 61.99+/-15.72 microg/l (p=0.427); mid RT 104.75+/-31.41 microg/l vs. 62.37+/-16.23 microg/l (p<0.001); end RT 100.63+/-31.12 microg/l vs. 62.29+/-16.11 microg/l (p<0.001); 6 weeks after RT 72.73+/-26.53 microg/l vs. 64.17+/-17.22 microg/l (p=0.170). CONCLUSION: The used dosage of 500 microg sodium selenite per day is sufficient to treat selenium deficiency during radiotherapy. After substitution, the patient returns to their individual selenium status.

Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology.

PURPOSE: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84µg/L were randomized before RT either to receive 500 µg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 µg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

[Radiotherapy in painful gonarthrosis. Results of a national patterns-of-care study]. / Strahlentherapie bei schmerzhafter Kniegelenkarthrose (Gonarthrose): Ergebnisse einer deutschen Patterns-of-Care-Studie

BACKGROUND AND PURPOSE: After a patterns-of-care study (PCS) in 2003/2004 addressing benign disorders in general, the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) conducted several multicenter cohort studies including the use of radiotherapy (RT) in painful gonarthrosis (GNA). MATERIAL AND METHODS: From 2006 to 2008, a PCS for GNA was conducted in all German RT institutions using a standardized structured questionnaire. Patient accrual, patient number, pretreatment, pain record, treatment indications, RT technique, and target volume concepts for painful GNA were assessed. In addition, the long-term functional and subjective outcomes were evaluated. RESULTS: 238/248 institutions (95.9%) returned the questionnaire: 50 (21%) reported no clinical experience with RT in GNA, while 188 (79%) institutions treated 4,544 patients annually (median 15; range one to 846 cases per institution). Indications for treatment were acute pain symptoms in 18.9%, chronic pain in 95.3%, and treatment-refractory pain in 81.1%. The median total dose was 6 Gy (range 3-12 Gy), with a median single dose of 1 Gy (0.25-3 Gy). 40.4% of the institutions applied two fractions and 51.4% three fractions weekly. RT was delivered with orthovoltage units (25%), linear accelerators (79.6%), and cobalt-60 units (8.3%). 42 institutions evaluated the long-term clinical outcome in a total of 5,069 cases. Median pain reduction for at least 3 months was reported in 60% (5-100%), median pain reduction for at least 12 months in 40% (10-100%), and median persistent pain reduction in 27.8% (10-85%) of the treated patients. In 30% of patients (7-100%), a second RT series was applied for inadequate pain response or early pain recurrence. No radiogenic acute or chronic side effects were observed. CONCLUSION: This PCS comprises the largest number of cases reported for RT in painful and refractory GNA. Despite variations in daily RT practice, high response and low toxicity for this treatment in a very large number of painful and refractory GNA cases renders low-dose RT an effective conservative therapy which can be applied prior to surgical procedures.

Zinc concentrations in serum during head and neck cancer progression.

UNLABELLED: Reduced serum-zinc concentrations are well known as typical laboratory characteristics in advanced head and neck cancer. Our aim was to follow the development of this phenomenon during the disease. PATIENTS AND METHODS: A total of 21 patients were included in this pilot-study (1 female, 20 male). The median age was 64 years, range 43-80 years. The following tumour localizations were registered: 11 larynx, 4 oropharynx, 2 hypopharynx and 4 other. Serum zinc levels were registered at baseline and during the follow-up investigations using flame atomic absorption spectrometry. RESULTS: The median follow-up time was 17 months, range 6-43 months. During the follow-up, 9/21 patients died tumour-dependently, 2 patients were living with cancer, 8 patients showed NED, and a further 2 patients died of non-cancer related causes. The zinc concentration decreased from 0.76 mmol/l (0.48-1.07 mmol/l) to 0.55 mmol/l (0.32-1.01 mmol/l). Nine of 11 patients with cancer developed extremely low serum zinc concentration 4-6 weeks before dying. CONCLUSION: The serum zinc concentration may be a marker for definitive palliative situations in head and neck cancer patients.

Influence of amifostine on late radiation-toxicity in head and neck cancer--a follow-up study.

AIM: The late toxicities due to multimodal therapy of advanced head and neck cancers were analysed. The impact of cytoprotection with amifostine is the specific objective of this report. PATIENTS AND METHODS: A total of 851 patients (717 men, 134 women) with head and neck cancer were included in this prospective study. Of these patients, 519/851 had received amifostine before radio(chemo)therapy, while 332 control patients had not received any kind of cytoprotection before irradiation. Primary radiochemotherapy was performed in 282 patients and adjuvant radiation was administered in 569. The follow-up examination was carried out at our outpatient department 21.4 months (median, range 2.3 to 149 months) after the primary therapy. RESULTS: Late xerostomia was seen in 765/851 patients (89.9%). Altered taste was reported by 284/851 (33.5%). These symptoms were reduced significantly by amifostine. No influence was seen on interstitial lymph edema (48.4%), or stenosis of the cervical esophagus (20.4%). Secondary symptoms such as dysphagia (78.8%) also had a trend for reduction. CONCLUSION: The administration of amifostine offers an opportunity to reduce selected long-term toxicities for survivors of head and neck cancer.

Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs - a retrospective multicenter study of 502 patients.

A total of 502 patients treated between 1990 and 2002 with low-dose radiotherapy (RT) for painful heel spurs were analysed for prognostic factors for long-term treatment success. The median follow-up was 26 months, ranging from 1 to 103 months. Events were defined as (1) slightly improved or unchanged pain after therapy, or (2) recurrent pain sensations during the follow-up period. Overall 8-year event-free probability was 60.9%. Event-free probabilities of patients with one/two series (414/88) were 69.7%/32.2% (p<0.001); >58/ < or = 58 years (236/266), 81.3%/47.9% (p=0.001); high voltage/orthovoltage (341/161), 67.9%/60.6% (p=0.019); pain anamnesis < or = 6 months/ >6 months (308/194), 76.3%/43.9% (p=0.001); single dose 0.5/1.0 Gy (100/401), 86.2%/55.1% (p=0.009); without/with prior treatment (121/381), 83.1%/54.9% (p=0.023); men/women (165/337), 61.2%/61.5% (p=0.059). The multivariate Cox regression analysis with inclusion of the number of treatment series, age, photon energy, pain history, single-dose and prior treatments revealed patients with only one treatment series (p<0.001), an age >58 years (p=0.011) and therapy with high voltage photons (p=0.050) to be significant prognostic factors for pain relief. Overall low-dose RT is a very effective treatment in painful heel spurs.

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.

Tumor markers and lymphatic metastasis in head and neck cancer patients.

OBJECTIVE: This study was conducted to evaluate the relationship between the lymph node status and tumor marker status in patients with histologically confirmed head and neck cancer. MATERIALS AND METHODS: 134 patients were included in this retrospective analysis. 33/134 were classified as NO and 101/134 as N+. The wall of the lymph node was ruptured by the metastasis in 70/134 patients (poor prognosis). We analyzed the sensitivity of squamous cell carcinoma antigen (SCC), carcinoembryotic antigen (CEA) and CYFRA 21-1 in the total population and in the subgroups. RESULTS: We observed elevated SCC levels in 21.6%, CEA levels in 23.9% and CYFRA 21-1 levels in 50.0% of all patients. If there was no lymphatic metastasis, the SCC sensitivity was 15.1%, the CEA sensitivity was 21.2% and the CYFRA 21-1 sensitivity was 36.4%. Lymph node-positive disease had increased SCC levels in 23.8% of the patients, increased CEA levels in 24.8% and increased CYFRA 21-1 levels in 54.5%. The subgroup of patients with ruptured lymph nodes had the following sensitivities: SCC 18.6% CEA 8.6%, and CYFRA 21-1 50.0%. CONCLUSION: No significant relationship between the lymph node metastasis and the elevation of tumor markers in patients with advanced head and neck cancer was found.

Serum selenium in head and neck cancer patients--a new marker of tumor activity?

OBJECTIVE: The purpose of this work was to investigate the relationship between the tumor volume and the endogenous selenium levels in untreated head and neck cancer patients. MATERIALS AND METHODS: One hundred consecutive patients were included in this study. We measured the endogenous levels of selenium in the serum and the whole blood of all patients by atomic absorption spectrometry. Additionally, the activity of glutathione peroxidase and the concentration of malonedialdehyde were observed. The resectability of the tumor was used as an independent marker of the tumor volume. RESULTS: Thirty-one out of 100 patients had resectable tumors, while 69 patients were characterized as unresectable. The following median results were obtained (resectable versus unresectable): Serum Se 0.90 micromol/l versus 0.78 micromol/l (p=0.024); whole blood Se 1.00 micromol/l versus 0.93 micromol/l (p=0.139); glutathione peroxidase 145 U/l versus 148 U/l (p=0.93); and malonedialdehyde 2.21 mmol/l versus 2.6 mmol/l (p=0.84). CONCLUSION: The concentration of serum selenium shows a significant relationship with tumor resectability in patients with advanced head and neck cancer.

Selenium in the treatment of radiation-associated secondary lymphedema.

PURPOSE: The aim of this explorative study was to evaluate the impact of selenium in the treatment of lymphedema after radiotherapy. MATERIALS AND METHODS: Between June 1996 and June 2001, 12 patients with edema of the arm and 36 patients with edema of the head-and-neck region were treated with selenium for therapy-related lymphedema. Of these 36 patients, 20 had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received sodium selenite over 4 to 6 weeks. RESULTS: Self-assessment using a visual analog scale (n = 48) showed a reduction of 4.3 points when comparing pre- and posttreatment values (p < 0.05). Of 20 patients with endolaryngeal edema, 13 underwent no tracheostomy, 5 underwent a temporary tracheostomy, and only 2 underwent a permanent tracheostomy. Ten of 12 patients with arm edema showed a circumference reduction of the edematous limb and improvement in the Skin-Fold Index by 23.3 points. An improvement of one stage or more was shown by the Földi or the Miller score (n = 28) in 22 (Földi score) and in 24 (Miller score) patients. CONCLUSIONS: Treatment with sodium selenite is well tolerated and easy to deliver. Additionally, our results suggest that sodium selenite has a positive effect on secondary-developing lymphedema caused by radiation therapy alone or by irradiation after surgery.

High-dose-rate brachytherapy in the treatment of recurrent and residual head and neck cancer.

OBJECTIVES/HYPOTHESIS: Interstitial and endocavitary brachytherapy are well-accepted kinds of radiotherapy that are commonly used in recurrent head and neck cancer. Most reports about brachytherapy in the successful treatment of head and neck tumors used low-dose-rate brachytherapy. There are only a few reports about high-dose-rate brachytherapy (HDRBT) in head and neck cancer patients. METHODS: After 10 years of experience with HDRBT with Ir 192, we have analyzed the results regarding response rates, survival time, and side effects. Between 1991 and 2000, 90 consecutive patients (68 men, 22 women) were treated with interstitial (68 patients) or intracavitary (22 patients) HDRBT in the head and neck area. Primary tumor locations were as follows: oropharynx (n = 26), tongue/floor of mouth (n = 22), nasopharynx (n = 10), nose/paranasal sinuses (n = 9), salivary glands (n = 5), hypopharynx (n = 5), CUP syndrome (n = 5), and others (n = 8). High-dose-rate brachytherapy was administered in 51 patients with recurrent disease and in 32 patients with residual tumor after primary radiochemotherapy. Seven patients were given exclusive HDRBT in a primary palliative situation. The single dose per fraction ranged from 1.5 to 7.5 Gy (median value, 5 Gy), and the total HDRBT dose ranged from 4.0 to 42.0 Gy (median value, 17.5 Gy). RESULTS: The overall remission rate was 81% with a 46% rate of complete remissions. We observed no change in or progression of tumor in 17 cases (19%). The rate of complete remissions (and median overall survival time) was different in the three therapy groups: in case of recurrent disease, 28% (6 mo); in case of residual tumor, 84% (25 mo); and in primary palliative brachytherapy, 0% (1 mo). Late toxicities III and IV (radiation treatment oncology group score) occurred in 6 of 90 (6.7%) patients. CONCLUSIONS: High-dose-rate brachytherapy proved to be an effective treatment modality in locoregional recurrent head and neck cancer. In cases with persistent or residual tumor after primary radiochemotherapy a local boost with brachytherapy can improve the chance of cure of tumor disease.

Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer.

The authors discuss the results of 3 studies of their group reflecting the possible role of amifostine in simultaneous radiochemotherapy (RCT) of advanced head and neck cancer. In a controlled phase II trial (1995 through 1996), 39 patients were included in this pilot investigation. A control group (n = 14) received simultaneous RCT of the head and neck region with an irradiation dose of 60 Gy and 2 cycles of carboplatin (700 mg/m(2) cumulative dose). Twenty-five patients received the same basic therapy and an additional 500-mg dose of amifostine before each chemotherapy. Amifostine was administered less than 45 minutes before the end of radiotherapy. The authors observed a dramatic reduction of typical radiotherapy-associated toxicities (mucositis, xerostomia, loss of taste, dysphagia). The hematologic side effects (leukocytopenia, anemia, thrombocytopenia) also were decreased significantly. The overall survival rate and locoregional control of both groups were comparable after 12 months. In a controlled intensification trial (1997 through 1999), the authors included 76 consecutive patients (69 men, 7 women) with pharyngeal cancer (oropharynx, n = 33; hypopharynx, n = 43). The tumors were characterized as unresectable and locally advanced without distant metastasis. All patients received a conventional radiotherapy (2-Gy single dose, daily fractionation) up to doses of 60 Gy and an additional 10 Gy as a boost in the tumor-infiltrated region. A dose of carboplatin, 70 mg/m(2), was given to a group of 45 patients on days 1 through 5 and 29 through 33 of radiotherapy (RCT arm). The resulting cumulative dose was 700 mg/m(2). A group of 31 patients (RCTintens arm) received the same dose of carboplatin on days 1 through 5, 22 through 26, and 43 through 47 or 1 through 5, 15 through 19, 29 through 33, and 43 through 47 of radiotherapy (cumulative dose 1.05 to 1.40 mg/m(2)). All patients received 500 mg of amifostine before each carboplatin administration. If the tumor volume was less than 20 cm(3), we observed an increased 1-year overall survival rate (91% v 71%) and time to progression (17 months v 10 months). If the tumor volume was greater than 20 cm(3), we observed comparable treatment results in both groups (1-year survival rate, 60% v 61%; time to progression, 13 months v 12 months). In a long-term follow-up investigation (1999 through 2000), 531 patients (89 women, 442 men) were analyzed according to their toxicities during regular follow-up investigations at our outpatient facility. All patients were treated by surgery or radio(chemo)therapy because of an advanced head and neck cancer. A total of 218 of 531 patients received the antineoplastic therapy without cytoprotection. An additional 313 patients received their RCT combined with amifostine administration before administration of the radiosensitizer. A significant influence of cytoprotection was registered in the following toxicities: xerostomia, fibrosis, loss of taste, and dysphagia. No impact was seen on the development of interstitial lymph edema and esophageal stenosis. Amifostine could be integrated in simultaneous radiochemotherapy of advanced head and neck cancer patients. The authors favor the administration of amifostine before chemotherapeutics alone. Selective cytoprotection could decrease the main acute toxicities (mucositis, xerostomia, dysphagia) as well as late side effects (xerostomia, loss of taste, fibrosis) of this form of combined treatment. The enhanced therapeutic index may be changed into a prognostic benefit for selected patients with unresectable tumors, if the volume is smaller than 20 cm(3).