Physical exercise and fatigue in advanced gastrointestinal cancer during chemotherapy.

OBJECTIVES: This study was aimed to analyse the effect of a patient-oriented modality of physical exercise (programmed and directed physical exercise (PDPE)) on cancer-related fatigue (CRF) and quality of life (QoL). The secondary aim was to evaluate changes in body composition and skeletal muscle function during the study in patients with and without PDPE. METHODS: A prospective randomised study was conducted to analyse the impact of PDPE on CRF and QoL. Patients were selected before the development of CRF to set the intervention before its appearance. A high probability CRF population was chosen: patients with advanced gastrointestinal cancer undergoing chemotherapy with weight loss (≥5%) over the last 6 months. PDPE consisted of a programme of exercise delivered weekly and adjusted to patients' medical conditions. Four visits were planned (weeks 0, 4, 8 and 12). QoL, CRF, body composition and skeletal muscle function were evaluated in each visit. RESULTS: From 101 patients recruited, 64 were considered evaluable, with three or four visits completed (n=30 control, n=34 PDPE group). Satisfactory compliance of ≥50% to the PDPE programme was seen in 47%. A reduction in the severity of fatigue was detected in the PDPE group (p=0.019), being higher in the subgroup of satisfactory compliance (p<0.001). This latter group showed better results of QoL in comparison with the control group (p=0.0279). A significant increase in endurance was found in the PDPE group (p<0.001). CONCLUSION: PDPE reduced the severity of fatigue and improved QoL. The difference in endurance would explain the results seen in the severity of fatigue.

The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases.

Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.

Does physical exercise improve quality of life of advanced cancer patients?

PURPOSE OF REVIEW: We discuss the principal issues about physical activity in advanced cancer patients through the analyses of the last articles and our experience in this field. RECENT FINDINGS: The efficacy of exercise training intervention could improve quality of life (QOL), fatigue and well being in advanced cancer patients. Several published studies have included, nevertheless, patients with early stage of disease and more recently, populations of patients with local advanced tumors of the breast, rectum and lung, who are undergoing neoadjuvant therapy. Despite the insufficient sample of patients in these studies, physical exercise is considered to improve both cardiopulmonary function and physical muscle fitness. Cancer-related fatigue is a devastating symptom in advanced cancer patients that implies loss of mobility and independence. SUMMARY: Physical exercise could be a treatment to increase skeletal muscle endurance and improve well being. In palliative medicine, physical activity could be applied to medical assistance or to design prospective and controlled trials so as to evaluate possible usefulness.

Specific nutritional supplement (Supportan®) in the supportive care of the radio-chemotherapy treatment of head and neck cancers: biochemical parameters. Preliminary study.

BACKGROUND: This is a preliminary study of a specific nutritional supplement -Supportan(®) - for the clinical support of patients with locally advanced head and neck (H&N) cancers who underwent treatment with concurrent radiochemotherapy (RT-CHT). MATERIAL AND METHODS: Seven patients received nutritional supplement (Supportan(®)) plus habitual diet during a median time of treatment with RT on 7.8 weeks plus concurrent weekly CHT(S). Specific serum protein fractions as a potential useful tool to evaluate the nutritional status were determined. The main objective was to assess the compliance with the above-mentioned treatment. RESULTS: Patients completed the nutritional support, 5 / 7 patients via oral route and 2/7 patients through nasogastric tube. All studied patients, that completed treatment, had not severe mucositis -ulcera, hemrraghe and/ or infection. None of them had another severe toxicity by treatment nor had impairment of Pefomance Status. No differences in all specific sera proteins were observed between S and To. CONCLUSION: In this preliminary study of few patients, we have observed a potential usefulness of Supportan(®) in the compliance of concurrent RT-CHT in patients with H&N cancers; moreover, its administration was useful to maintain the initial biochemical nutritional profile.

Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated.

CONTEXT: Cancer patients with dyspnea may be able to have the symptom pharmacologically controlled while its underlying cause is sought or treated. OBJECTIVES: This study was done to determine whether symptom control can be achieved while the cause is evaluated or treated and whether morphine or midazolam would be more suitable in this setting. METHODS: Sixty-three ambulatory patients with advanced cancer and dyspnea were clinically characterized and then randomized to receive either oral morphine or oral midazolam. A fast in-clinic drug titration scheme was implemented followed by an ambulatory five-day period in which the patients received the effective dose that relieved their dyspnea. During this period, the patients were followed daily while the underlying causes of dyspnea were sought out or treated. RESULTS: Thirty-one patients with dyspnea entered the morphine arm and 32 patients entered the midazolam one. During the initial in-clinic phase, dyspnea was alleviated by at least 50% in all patients, whether they received morphine or midazolam. During the ambulatory phase, midazolam was superior to morphine in controlling baseline and breakthrough dyspnea. Both treatments were well tolerated, with mild somnolence being the most common adverse event. Neither morphine nor midazolam affected the outcome and/or implementation of additional diagnostic and/or therapeutic interventions. CONCLUSION: Our results suggest that cancer-related dyspnea in ambulatory patients can be pharmacologically treated while its most probable specific cause is sought and/or while an etiology-oriented intervention is implemented. In this setting, midazolam appeared to be a better option than morphine for the immediate and long-term relief of the symptom.

Experiencia de 20 años en tratamiento conservador del cáncer de laringe estadio III y IV operable del equipo multidisciplinario del Instituto Angel H Roffo / 20 Years experience with organ preservation in resecable stage III and IV laryngeal cancer by a multidisciplinary of them the

The classic treatment of the laryngeal resectable stage III and IV epi-dermoid cancer is: surgery followed by adjuvant radiotherapy. Only on scarce occasions these patients can accede to organ preservation conserving correct phonetics and deglution with absence of aspiration. In most of the occasions the procedure of choice is total laryngectomy with or without cervical emptying if it is necessary. Since the end of the 80s. we have developed strategies for organ preservation of the tumors of the head and neck. Despite the implementation of the neoadjuvant chemotherapy and the later use of chemoradiotherapy simultaneously or the introduction of monoclonal antibodies anti EGFR (anti epidemic growth receptor factor), the rate of survival of the tumors in resectabale stage III and IV epidermoid carcinoma remains stable. The authors present their experience with the management of these patients, considering that the two main objectives for the development of new strategies for the treatment of laryngeal cancer are to raise the rate of survival, and the rate of larynx preservation. La rynx preservation using induction chemotherapy plus radiation therapy, and preservation in cases of advance laryngeal cancer treated with platinum, are also considered. Preservation using neoadjuvant chemotherapy is also detailed. The authors presents their experience with the management of these patients.(AU)

Experiencia de 20 años en tratamiento conservador del cáncer de laringe estadio III y IV operable del equipo multidisciplinario del Instituto Angel H Roffo / 20 Years experience with organ preservation in resecable stage III and IV laryngeal cancer by a multidisciplinary of them the

The classic treatment of the laryngeal resectable stage III and IV epi-dermoid cancer is: surgery followed by adjuvant radiotherapy. Only on scarce occasions these patients can accede to organ preservation conserving correct phonetics and deglution with absence of aspiration. In most of the occasions the procedure of choice is total laryngectomy with or without cervical emptying if it is necessary. Since the end of the '80s. we have developed strategies for organ preservation of the tumors of the head and neck. Despite the implementation of the neoadjuvant chemotherapy and the later use of chemoradiotherapy simultaneously or the introduction of monoclonal antibodies anti EGFR (anti epidemic growth receptor factor), the rate of survival of the tumors in resectabale stage III and IV epidermoid carcinoma remains stable. The authors present their experience with the management of these patients, considering that the two main objectives for the development of new strategies for the treatment of laryngeal cancer are to raise the rate of survival, and the rate of larynx preservation. La rynx preservation using induction chemotherapy plus radiation therapy, and preservation in cases of advance laryngeal cancer treated with platinum, are also considered. Preservation using neoadjuvant chemotherapy is also detailed. The authors presents their experience with the management of these patients.

Continuous hyperfractionated accelerated radiation therapy week-end less in combination with neoadjuvant chemotherapy for the treatment of stage III non-small-cell lung cancer.

PURPOSE: Current treatment for unresectable stage III lung cancer includes standard radiotherapy with chemotherapy. Continuous hyperfractionated radiotherapy has been shown to be more effective than standard radiotherapy but may be associated with increased toxicity. In this study, we evaluated the feasibility and outcomes of patients treated with a hyperfractionated accelerated regimen in combination with neoadjuvant chemotherapy. METHODS AND MATERIALS: We prospectively studied 61 consecutive patients with unresectable stage III non-small-cell lung cancer. All patients received three dimensional conformal radiotherapy using three daily fractions of 1.5 Gy to a total dose of 54-60 Gy omitting elective mediastinal irradiation. Approximately two-thirds of the patients also received platinum-based neoadjuvant chemotherapy. The primary outcome was locoregional disease-free survival. Secondary analyses were performed to assess tolerability, response rates, and overall and disease-free survival among study participants. RESULTS: Overall, 56% of patients had a complete response. Locoregional recurrence was observed in 55% of patients with only a 3% rate of dissemination to non-irradiated mediastinal lymph nodes. Median locoregional disease-free survival, disease-free survival, and overall survival were 16 months (95% CI: 12-20), 15 months (95% CI: 12-18), and 19 months (95% CI: 15-30), respectively. Additionally, no episodes of severe toxicity were reported among study participants. Poor performance status and radiation response were independent predictors of survival. CONCLUSIONS: This study suggests that conformal three-dimensional hyperfractionated accelerated radiotherapy omitting elective node irradiation can be used in combination with neoadjuvant chemotherapy to treat patients with stage III lung cancer. Future studies should compare this approach with the standard treatments for patients with stage III lung cancer.

Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer.

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.

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.

Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin.

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.

Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer.

The mainstay of dyspnea palliation remains altering its central perception. Morphine is the main drug and anxiolytics have a less established role. This trial assessed the role of midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in terminally ill cancer patients. One hundred and one patients with severe dyspnea were randomized to receive around-the-clock morphine (2.5 mg every 4 hours for opioid-naïve patients or a 25% increment over the daily dose for those receiving baseline opioids) with midazolam rescue doses (5 mg) in case of breakthrough dyspnea (BD) (Group Mo); around-the-clock midazolam (5 mg every 4 hours) with morphine rescues (2.5 mg) in case of BD (Group Mi); or around-the-clock morphine (2.5 mg every 4 hours for opioid-naïve patients or a 25% increment over the daily dose for those receiving baseline opioids) plus midazolam (5 mg every 4 hours) with morphine rescue doses (2.5 mg) in case of BD (Group MM). All drugs were given subcutaneously in a single-blinded way. Thirty-five patients were entered in Group Mo, 33 entered in Mi, and 33 entered in MM. At 24 hours, patients who experienced dyspnea relief were 69%, 46%, and 92% in the Mo, Mi, and MM groups, respectively (P = 0.0004 and P = 0.03 for MM vs. Mi and MM vs. Mo, respectively). At 48 hours, those with no dyspnea relief (no controlled dyspnea) were 12.5%, 26%, and 4% for the Mo, Mi, and MM groups, respectively (P = 0.04 for MM vs. Mi). During the first day, patients with BD for the groups Mo, Mi, and MM were 34.3%, 36.4%, and 21.2%, respectively (P = NS or not significant), whereas during the second day, these percentages were 38%, 38.5%, and 24%, respectively (P = NS). The data demonstrate that the beneficial effects of morphine in controlling baseline levels of dyspnea could be improved with the addition of midazolam to the treatment.

Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases.

PURPOSE: The primary goal of this phase I/II study was to evaluate the feasibility, safety and efficacy of celecoxib administered concomitant to radiotherapy to treat unresectable BM. PATIENTS AND METHODS: Patients with measurable BM by CT or MRI, unresectability criteria by a neurosurgeon and RPA-RTOG class II were eligible. Celecoxib was administered at 400 mg/day during the entire course of radiotherapy. All patients were irradiated with 60Co beams to whole-brain dose of 32 Gy (20 fractions of 1.6 Gy each two times a day with a 6 h interval between treatments) followed by a 22.4 Gy boost (same fractionation schedule) over evident lesions. RESULTS: Twenty-seven patients were treated. The concurrent regimen was well tolerated with 15 cases of mild dyspepsia. Alopecia (NCI grades 1-2) was the most important side effect. Three patients presented rash/desquamation of moderate intensity. Radiological responses occurred in 18 of 25 valuable patients (72), with five complete responses (CR). Symptomatic responses were reported in 25 of 27 patients (92.6), with 20 CR. The overall response rate (considering complete plus partial responses) was 66.7. Percentile 50 for time-to-progression, time-to-neurological-progression and functional-independence-time were 3, 6.25 and 6.7 months, respectively. Median survival time was 8.7 months. CONCLUSION: Our initial results suggest that radiotherapy plus celecoxib is safe and a possible active treatment for patients with BM. Further investigation in a randomized trial is warranted to validate its clinical utility.

Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study.

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with evidence of SIMS were studied. SIMS was defined as the presence of weight loss, anorexia, fatigue performance status>/=2 and acute-phase protein response. Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200 mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13 patients either had stable weight (+/- 1%) or had gained weight. There were significant differences in improvement of body-weight-change rate, nausea, early satiety, fatigue, appetite and performance status. Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma, treated with MPA, celecoxib and dietary intervention, might have considerable improvement in certain SIMS outcomes. This multitargeted symptomatic approach deserves further study.

Potential utility of the peripheral analgesic properties of morphine in stomatitis-related pain: a pilot study.

To determine the potential clinical utility of peripheral opioid action using a clinical model of cancer treatment-induced inflammation and pain that allowed for topical application of morphine in the damaged tissue (oral mucosa). This pilot study followed a two blocks design. Ten patients with painful oral mucositis were enrolled in the first block (dose-response relationship finding) and randomized in two groups to receive oral rinses with 15 ml of either 1 per thousand or 2 per thousand morphine solution. Twenty-two patients were enrolled into the second block (efficacy and safety determination). Additionally, serum concentrations of morphine were measured in five representative patients. In the first block (n=10) a dose-response relationship for topical morphine was found. Rinses with 2 per thousand -morphine solution showed better pain relief (median 80%, range 70-80%) than those with 1 per thousand (median 60%, range 55-70%; P=0.0238). Therefore, subsequent patients enrolled for the second block (n=22) received oral rinses with 2 per thousand -morphine solution. In these patients the time to good (>or=50%) or to complete (100%) pain relief was 28 (+/-12)min after the first mouthwash, and the duration of relief was on average 216 (+/-25)min. Twenty patients (90%) received the successive mouthwashes every 3 h and 10% of them every 2 h. The duration of severe pain at the moment of swallowing was 5.17 (+/-1.47) days. Only six patients needed supplementary analgesia, and the time elapsed before the first supplemental analgesic was 1.18 (+/-0.8) days. The duration of severe functional impairment was 1.52 (+/-1.31) days, thus allowing us to feed the patient by mouth with liquid-food supplementation. During our experiment no systemically active detectable concentrations of morphine were found (GC-MS analysis). The most important side effect attributable to morphine mouthwashes was burning/itching sensation (very mild to mild intensity). Patients with painful chemoradiotherapy-induced stomatitis could be alleviated using topical morphine mouthwashes.

Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma.

BACKGROUND: Oral mucositis is the dose-limiting toxicity for patients receiving concurrent chemoradiotherapy regimens for tumors of the head and neck area. Currently, the management of established mucositis includes the use of topical anesthetics and systemic analgesics. Based on the clinical evidence of pain alleviation by topical morphine in patients with some inflammatory and painful conditions, a clinical study was undertaken to determine this effect on mucositis-associated pain. METHODS: Twenty-six patients with head and neck malignancies treated with concomitant chemoradiotherapy for head and neck carcinoma who had severe painful mucositis (World Health Organization Grade 2 or higher) were enrolled. Patients were randomly assigned to morphine mouthwash (MO; 14 patients) or magic mouthwash (MG), a mixture of equal parts of lidocaine, diphenhydramine, and magnesium aluminum hydroxide (12 patients). RESULTS: The duration of severe pain was 3.5 days less in the MO group compared with the MG group (P = 0.032). The intensity of oral pain was also significantly lower in the MO group compared with the MG group (P = 0.038). No patient in the MO group required third-step opiates for alleviation of the mouth pain. There was a significant difference in duration of severe functional impairment (P = 0.017). Five patients in the MG group complained of local side effects and only one in the MO group (P = 0.007). CONCLUSIONS: For patients with head and neck carcinomas receiving concomitant chemoradiotherapy, MO is a simple and effective treatment to decrease the severity and duration of pain and the duration of functional impairment.