Allopurinol mouth rinse for prophylaxis of fluorouracil‐induced mucositis

PANAHI Y., ALA S., SAEEDI M., OKHOVATIAN A., BAZZAZ N. & NAGHIZADEH M.M. (2010) European Journal of Cancer Care 19 , 308–312
Allopurinol mouth rinse for prophylaxis of fluorouracil‐induced mucositis To prepare and evaluate an allopurinol mouth rinse for prophylaxis of fluorouracil‐induced mucositis, 33 patients with malignant disorders, who were going to receive 5‐fluorouracil containing chemotherapy, were enrolled in a placebo‐controlled double‐blinded randomized clinical trial. Allopurinol mouthwash (1 mg/ml) or placebo was administered 1, 2 and 3 h after chemotherapy and three consecutive nights. A questionnaire consisting of demographic parameters, medical status, quality of life survey and mucosal injury scoring table (based on World Health Organization scales for mucositis) was completed for each patient at Day 1, 3 and 7 after chemotherapy. In allopurinol group nine participants (60.0%) were female and in placebo group, 10 (66.7%) (P = 0.705). Mean ages were 56.9 ± 10.3 and 49.5 ± 13.8 years in allopurinol and placebo groups respectively (P = 0.107). The analysis showed that the higher education level and the use of dentures significantly reduced the occurrence of mucositis, and allopurinol mouth rinse (1 mg/ml) was ineffective in the prophylaxis of fluorouracil‐induced mucositis.     

Circadian variation in radiation‐induced intestinal mucositis in patients with cervical carcinoma

BACKGROUND:

Mucositis, a radiotherapy‐associated toxicity, is an important factor determining morbidity and treatment compliance. Gastrointestinal mucositis in patients undergoing radiotherapy may also depend on time of administration of radiation in addition to several other factors. The presence of any correlation between the severity of acute gastrointestinal mucositis in cervical carcinoma patients and the time of irradiation was prospectively evaluated.

METHODS:

A total of 229 patients with cervical carcinoma were randomized to morning (8:00‐10:00 AM ) and evening (6:00‐8:00 PM ) arms. The incidence of mucositis in the 2 arms was assessed and reported in terms of various grades of diarrhea.

RESULTS:

Overall (grade I‐IV) as well as higher grade (III and IV) diarrhea was found to be significantly increased in the morning arm as compared with the evening arm (overall: 87.39 % vs 68.18 %, P < .01; higher grade: 14.29% vs 5.45%, P < .05). Other radiation‐induced toxicity was also higher in the morning arm, but its occurrence in the 2 arms did not differ significantly (13.45% vs 12.73%, P > .05). After completion of treatment, patients' response to radiation in the 2 arms was similar (P > .05).

CONCLUSIONS:

The significant difference in the incidence of higher grade diarrhea between the morning and evening arms is indirect evidence of the influence of circadian rhythm on the intestinal mucosa of the human intestine. This knowledge may facilitate treating patients with decreased toxicity to the intestinal mucosa. Cancer 2010. © 2010 American Cancer Society.     

Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study

PURPOSE: To determine the effect of oral zinc sulphate supplementation on radiation-induced oropharyngeal mucositis in patients with head-and-neck cancer. MATERIALS AND METHODS: Thirty patients with head-and-neck cancer were randomly assigned to receive either zinc sulfate or placebo. Primary tumors were localized in the larynx in 14 patients, in the nasopharynx in 4, in the oral cavity in 4, in a salivary gland in 1, in the maxillary sinus in 1, in neck nodes (lymphoma presenting primarily) in 3 and in neck metastases from an unknown primary in 3. In the placebo group, 3 patients were excluded; 1 patient died during treatment, 1 left the study, and 1 did not come to the 6 week control visit. The patients were treated with telecobalt radiotherapy at conventional fractionation (2 Gy/fraction, five fractions weekly, for 20-35 fractions within 4-7 weeks). The median radiation dose was 6400 cGy (4000-7000 cGy). Oral mucositis was assessed by two independent physicians, experts in radiation oncology, using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. RESULTS: In the zinc sulfate group, Grade 3-4 mucositis was not detected in any patient; Grade 0 mucositis was detected in 2, and Grade 1 in 8, and Grade 2 in 5 patients. In the placebo group, Grade 2 mucositis was detected in 4 and Grade 3 in 8 patients. We observed that the degree of mucositis in the patients in the zinc sulfate group was significantly lower than that in the placebo group (p < 0.05). Confluent mucositis developed earlier in the placebo group than in the zinc sulfate group after the onset of treatment (p < 0.05) and started to improve sooner in the zinc sulfate group than in the placebo group (p < 0.05). CONCLUSIONS: Zinc sulfate is beneficial in decreasing the severity of radiation-induced mucositis and oral discomfort. These results should be confirmed by additional evaluation in randomized studies with a larger number of patients.     

Therapeutic effect of recombinant human epidermal growth factor (rhEGF) on mucositis in patients undergoing radiotherapy,with or without chemotherapy,for head and neck cancer

BACKGROUND:

We evaluated the efficacy of topically applied human recombinant epidermal growth factor (rhEGF) for the treatment of oral mucositis induced by radiotherapy (RT), with or without chemotherapy, in patients with head and neck cancer.

METHODS:

Patients receiving definitive chemoradiotherapy, definitive RT, or postoperative RT to the oral cavity or oropharynx were recruited from 6 institutions and enrolled in a randomized, double‐blind, placebo‐controlled phase 2 trial. Patients were assigned to a placebo group or to 1 of 3 EGF‐treatment groups (10, 50, or 100 μg/mL doses, delivered in a spray, twice daily). The grade of mucositis was evaluated using the Radiation Therapy Oncology Group (RTOG) scoring criteria. Responders to EGF were defined as having an RTOG grade of 2 or lower at the fourth‐ or fifth‐week examinations during RT, but an enduring RTOG grade 2 for 2 weeks was an exception.

RESULTS:

Of the 113 patients included in the study, 28 received placebo and 29 received EGF at 10 μg/mL, 29 at 50 μg/mL, and 27 at 100 μg/mL. EGF significantly reduced the incidence of severe oral mucositis at the primary endpoint (a 64% response was observed with 50 μg/mL EGF vs a 37% response in the control group; P = .0246).

CONCLUSIONS:

The EGF oral spray may have potential benefit for oral mucositis in patients undergoing RT for head and neck cancer. Phase 3 studies are ongoing to confirm these results. Cancer 2009. © 2009 American Cancer Society.     

Single‐fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases—Equivalent efficacy,less toxicity,more convenient

BACKGROUND:

The Radiation Therapy Oncology Group (RTOG) trial 97‐14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single‐fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM.

METHODS:

PVBM included the cervical, thoracic, and/or lumbar spine regions. Among patients with PVBM, differences in retreatment rates and in pain relief, narcotic use, and toxicity 3 months after randomization were evaluated.

RESULTS:

Of 909 eligible patients, 235 (26%) had PVBM. Patients with and without PVBM differed in terms of the percentage of men (55% vs 47%, respectively; P = .03) and the proportion of patients with multiple painful sites (57% vs 38%, respectively; P < .01). Among those with PVBM, more patients who received MFRT had multiple sites treated (65% vs 49% for MFRT vs SFRT, respectively; P = .02). There were no statistically significant treatment differences in terms of pain relief (62% vs 70% for MFRT vs SFRT, respectively; P = .59) or freedom from narcotic use (24% vs 27%, respectively; P = .76) at 3 months. Significant differences in acute grade 2 through 4 toxicity (20% vs 10% for MFRT vs SFRT, respectively; P = .01) and acute grade 2 through 4 gastrointestinal toxicity (14% vs 6%, respectively; P = .01) were observed at 3 months, with lower toxicities seen in the patients treated with SFRT. Late toxicity was rare. No myelopathy was recorded. SFRT produced higher 3‐year retreatment rates (5% vs 15%; P = .01).

CONCLUSIONS:

Results for the subset of patients with PVBM in the RTOG 94‐17 randomized controlled trial were comparable to those for the entire population. SFRT produced less acute toxicity and a higher rate of retreatment than MFRT. SFRT and MFRT resulted in comparable pain relief and narcotic use at 3 months. Cancer 2013. © 2012 American Cancer Society.     

Efficacy of 4 weeks topical bifonazole treatment for onychomycosis after nail ablation with 40% urea: a double‐blind,randomized, placebo‐controlled multicenter study

Onychomycosis is a common fungal infection most often affecting the toenails. If untreated, it can cause discomfort sufficient to reduce quality of life. To evaluate efficacy and safety of bifonazole cream vs. placebo in onychomycosis treatment after non‐surgical nail ablation with urea paste. Fifty‐one study centres randomized 692 subjects with mild‐to‐moderate onychomycosis to receive bifonazole 1% cream or placebo for 4 weeks following non‐surgical nail ablation with urea 40% paste over 2–4 weeks. Efficacy of the two phase treatment was evaluated by overall cure of the target nail comprising clinical and mycological cure 2 weeks, 3 and 6 months after end of treatment. At 2 weeks (primary endpoint), overall cure rate was superior in bifonazole‐treated group (54.8% vs. 42.2% for placebo; P = 0.0024). The clinical cure rate was high in both treatment groups (86.6% bifonazole vs. 82.8% placebo), but proportion with mycological cure was higher with bifonazole treatment (64.5%) vs. placebo treatment 49.0%, (P = 0.0001). We observed higher early overall cure rate with 4 weeks topical bifonazole compared with placebo after removal of infected nail parts with urea. This two stage treatment was well tolerated and offers an additional option in topical onychomycosis therapy.     

Everolimus in advanced,progressive, well‐differentiated,non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

In the phase III RADIANT‐4 study, everolimus improved median progression‐free survival (PFS) by 7.1 months in patients with advanced, progressive, well‐differentiated (grade 1 or grade 2), non‐functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35‐0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT‐4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8‐10.9) months in the everolimus arm vs 3.6 (1.9‐5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28‐0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3‐4 drug‐related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well‐differentiated, non‐functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT‐4 cohort. These results support the use of everolimus in patients with advanced, non‐functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).     

Percutaneous endoscopic gastrostomy in oropharyngeal cancer patients treated with intensity‐modulated radiotherapy with concurrent chemotherapy

BACKGROUND:

The clinical benefit of routine placement of prophylactic percutaneous endoscopic gastrostomy (pPEG) tubes was assessed in patients with oropharyngeal cancer (OPC) who are undergoing intensity‐modulated radiotherapy (IMRT) with concurrent chemotherapy.

METHODS:

From 1998 through 2009, 400 consecutive patients with OPC who underwent chemoradiation were included. Of these, 325 had a pPEG and 75 did not (nPEG). Weight and albumin change from baseline to mid‐IMRT, end of IMRT, 1 month post‐IMRT, and 3 months post‐IMRT were evaluated. The treating physicians prospectively recorded acute and late toxicities.

RESULTS:

Significantly lower absolute weight loss at end of IMRT (6.80 kg vs 8.38 kg, P = .007), 1 month post‐IMRT (9.06 kg vs 11.33 kg, P = .006), and 3 months post‐IMRT (11.10 kg vs 13.09 kg, P = .044) was noted in the pPEG versus nPEG groups. This benefit in reduction of percent weight loss was consistently significant only among patients with BMI < 25. Significant differences were noted in hospital admission rate (15.1% vs 26.7%, P = .026) and volume of nonchemotherapy hydration (8.9 liters vs 17.2 liters, P = .004). There were no differences in percent albumin change, acute dysphagia, acute mucositis, acute xerostomia, chronic dysphagia, radiation treatment duration, and overall survival. Multivariate analysis noted age >55 years (P < .001), female sex (P < .001), and T3/4 category disease (P < .001) were significantly associated with prolonged PEG use.

CONCLUSIONS:

Although pPEG reduced absolute and percent weight loss and need for hospitalizations in our cohort of patients with OPC undergoing chemoradiation, no differences were noted in radiation treatment duration, toxicity, and overall survival. Prolonged PEG use correlated with age >55 years, female sex, and T3/T4 tumors. Cancer 2012. © 2012 American Cancer Society.     

Long‐term results (>25 years) of a randomized,prospective clinical trial evaluating chemotherapy in patients with high‐grade,operable osteosarcoma

BACKGROUND:

The authors present the long‐term follow‐up (>25 years) data from 1 of the original prospective, randomized trials that compared adjuvant chemotherapy with expectant management in patients with high‐grade, localized osteosarcoma. In addition, the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease‐free and overall survival.

METHODS:

Fifty‐nine patients with high‐grade, localized osteosarcoma were enrolled in a prospective trial that was performed between 1981 and 1984 at the University of California‐Los Angeles (UCLA). Patients were randomized to receive either adjuvant chemotherapy or observation after surgical resection. Long‐term outcomes, follow‐up, and pathologic review of all available histologic sections were performed.

RESULTS:

The 25‐year disease‐free survival rate was 28% for patients who received adjuvant chemotherapy compared with 15% for the untreated patients (P = .02). The overall survival rate at 25 years was also significantly higher for treated patients versus untreated patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of chemotherapy was a statistically significant predictor of overall survival and disease‐free survival for patients who received adjuvant therapy (164 months vs 65 months [P = .04] and 141 months vs 14 months [P < .01], respectively).

CONCLUSIONS:

Patients with high‐grade, localized osteosarcoma who received adjuvant chemotherapy after undergoing definitive surgical resection had a statistically significant benefit in disease‐free and overall survival that was maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant chemotherapy and radiation was predictive of overall survival and disease‐free survival in patients who received adjuvant chemotherapy. Cancer 2012. © 2012 American Cancer Society.     

Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients

Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer. However, radiation-induced changes in the oral cavity, such as xerostomia and mucositis, are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy, and attempts at ameliorating these side effects have been poor at best. Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09). In total, 245 evaluable patients were randomized to pilocarpine or placebo. Selected patients were required to have > or = 50% of the volume of the major salivary glands receive > or = 50Gy; to agree to provide stimulated and unstimulated samples of saliva (measured in g) before treatment, at the end of treatment, and 3 and 6 months after completion of radiation therapy; and to complete the University of Washington Head and Neck Symptom Scale. Following the completion of radiation therapy, the average unstimulated salivary flow was statistically greater in the pilocarpine group, whereas no difference was noted following parotid stimulation. There was no effect on the amelioration of mucositis. The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis. The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia. However, the absent correlation between improved salivary flow and QOL scores is of some concern (though not a new finding) and may be related to the existence of comorbidities and the lack of effect on mucositis.     

Effect of vitamin E on chemotherapy-induced mucositis and neutropenia in leukemic patients undergoing bone marrow transplantation

Aim: This study was conducted to investigate the effect of oral vitamin E on mucositis and neutropenia in patients with leukemia. Methods: This was a randomized double‐blind placebo controlled clinical trial of 60 patients with leukemia (acute lymphoblastic, acute myelogenous leukemia and chronic myelogenous leukemia) who were consecutive recipients of allogenic bone marrow transplantation (BMT), randomly assigned to receive 400 mg vitamin E twice daily (supplemented group) or placebo (control). The incidence and severity of mucositis and the mean duration of neutropenia were compared. Results: The mean duration of neutropenia and the incidence of the mucositis between the two groups was the same (P = 1.0). The difference between the placebo group and mucositis grade 1 (P = 0.31), grade 2 (P = 0.25), grade 3 (P = 0.93) and grade 4 (P = 0.32) was not statistically significant. Moreover the variables of age, sex, BMI and underlying disease had no effect. Conclusion: In this study supplementation with oral vitamin E had no effect on mucositis and neutropenia in patients with leukemia who were recipients of allogenic BMT. More interventional trials are warranted.     

Multi‐institutional retrospective study of mucoepidermoid carcinoma treated with carbon‐ion radiotherapy

This study aimed to evaluate the clinical outcomes of patients with mucoepidermoid carcinomas in the head and neck treated with carbon‐ion radiotherapy. Data from 26 patients who underwent carbon‐ion radiotherapy in four facilities were analyzed in this multi‐institutional retrospective study: the Japan Carbon‐ion Radiation Oncology Study Group. The median follow‐up time was 34 months. One patient experienced local recurrence, and the 3‐year local control rate was 95%. One patient developed lymph node recurrence and five developed distant metastases. The 3‐year progression‐free survival rate was 73%. Five patients died, two of mucoepidermoid carcinoma and three of intercurrent disease. The 3‐year overall survival rate was 89%. Acute mucositis and dermatitis of grade 3 or higher were experienced by 19% and 8% of patients, respectively; these improved with conservative therapy. Late mucositis and osteonecrosis of jaw were observed in 12% and 23% of patients, respectively. The 3‐year cumulative rate of any late adverse event of grade 3 or higher was 14%. None of the patients died of the acute or late adverse events. Carbon‐ion radiotherapy was efficacious and safe for treating mucoepidermoid carcinoma in this multi‐institutional retrospective study (registration no. UMIN000024473). We are currently undertaking a prospective multicenter study.     

Five‐year follow‐up of survival and relapse in patients who received cryotherapy during high‐dose chemotherapy for stem cell transplantation shows no safety concerns

SVANBERG A., ÖHRN K. & BIRGEGÅRD G. (2012) European Journal of Cancer Care Five‐year follow‐up of survival and relapse in patients who received cryotherapy during high‐dose chemotherapy for stem cell transplantation shows no safety concerns We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high‐dose chemotherapy for stem cell transplantation. The present study is a 5‐year follow‐up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high‐dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5‐year follow‐up study gave no support for safety concerns with cryotherapy.     

A retrospective multicenter study of carbon‐ion radiotherapy for major salivary gland carcinomas: Subanalysis of J‐CROS 1402 HN

A retrospective multicenter study was carried out to assess the clinical outcomes of carbon‐ion radiotherapy for head and neck malignancies (Japan Carbon‐Ion Radiation Oncology Study Group [J‐CROS] study: 1402 HN). We evaluated the safety and efficacy of carbon‐ion radiotherapy in patients with major salivary gland carcinoma. Sixty‐nine patients treated with carbon‐ion radiotherapy at four Japanese institutions were analyzed. Thirty‐three patients (48%) had adenoid cystic carcinomas, 10 (14%) had mucoepidermoid carcinomas, and 26 (38%) had other disease types. Three patients (4%) had T1 disease, 8 (12%) had T2, 25 (36%) had T3, and 33 (48%) had T4. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 27 mL. The median follow‐up period was 32.7 months. The 3‐year local control rate and overall survival rate were 81% and 94%, respectively. Regarding acute toxicities, seven patients had grade 3 mucositis and seven had grade 3 dermatitis. Regarding late toxicities, one patient had grade 3 dysphagia and one had a grade 3 brain abscess. No grade 4 or worse late reactions were observed. In conclusion, definitive carbon‐ion radiotherapy was effective with acceptable toxicity for major salivary gland carcinomas.     

Interleukin‐6 production mediated by the IRE1‐XBP1 pathway confers radioresistance in human papillomavirus‐negative oropharyngeal carcinoma

Endoplasmic reticulum stress (ERS) plays a key role in the pathogenesis and development of tumors and protects tumor cells from radiation damage and drug‐induced stress. We previously demonstrated that EGFR confers radioresistance in human papillomavirus (HPV)‐negative human oropharyngeal carcinoma by activating ERS signaling through PERK and IRE1α. In addition, PERK confers radioresistance by activating the inflammatory cytokine NF‐κB. However, the effect of IRE1 on radiosensitivity has not yet been fully elucidated. Here, we clarified that IRE1 overexpression was associated with poor outcome in HPV‐negative patients treated with radiotherapy (P = 0.0001). In addition, a significantly higher percentage of radioresistant HPV‐negative patients than radiosensitive HPV‐negative patients exhibited high IRE expression (66.7% vs 27.8%, respectively; P = 0.001). Silencing IRE1 and XBP1 increased DNA double‐strand break (DSB) and radiation‐induced apoptosis, thereby increasing the radiosensitivity of HPV‐negative oropharyngeal carcinoma cells. IRE1‐XBP1 silencing also inhibited radiation‐induced IL‐6 expression at both the RNA and protein levels. The regulatory effect of IRE1‐XBP1 silencing on DNA DSB‐induced and radiation‐induced apoptosis was inhibited by pretreatment with IL‐6. These data indicate that IRE1 regulates radioresistance in HPV‐negative oropharyngeal carcinoma through IL‐6 activation, enhancing X‐ray‐induced DNA DSB and cell apoptosis.     

Early clinical outcomes of helical tomotherapy/intensity‐modulated proton therapy combination in nasopharynx cancer

This study aimed to evaluate the feasibility of combining helical tomotherapy (HT) and intensity‐modulated proton therapy (IMPT) in treating patients with nasopharynx cancer (NPC). From January 2016 to March 2018, 98 patients received definitive radiation therapy (RT) with concurrent chemotherapy (CCRT). Using simultaneous integrated boost and adaptive re‐plan, 3 different dose levels were prescribed: 68.4 Gy in 30 parts to gross tumor volume (GTV), 60 Gy in 30 parts to high‐risk clinical target volume (CTV), and 36 Gy in 18 parts to low‐risk CTV. In all patients, the initial 18 fractions were delivered by HT, and, after rival plan evaluation on the adaptive re‐plan, the later 12 fractions were delivered either by HT in 63 patients (64.3%, HT only) or IMPT in 35 patients (35.7%, HT/IMPT combination), respectively. Propensity‐score matching was conducted to control differences in patient characteristics. In all patients, grade ≥ 2 mucositis (69.8% vs 45.7%, P = .019) and grade ≥ 2 analgesic usage (54% vs 37.1%, P = .110) were found to be less frequent in HT/IMPT group. In matched patients, grade ≥ 2 mucositis were still less frequent numerically in HT/IMPT group (62.9% vs 45.7%, P = .150). In univariate analysis, stage IV disease and larger GTV volume were associated with increased grade ≥ 2 mucositis. There was no significant factor in multivariate analysis. With the median 14 month follow‐up, locoregional and distant failures occurred in 9 (9.2%) and 12 (12.2%) patients without difference by RT modality. In conclusion, comparable early oncologic outcomes with more favorable acute toxicity profiles were achievable by HT/IMPT combination in treating NPC patients.     

Prophylaxis and management of acute radiation‐induced skin toxicity: a survey of practice across Europe and the USA

Radiation‐induced toxicity is a common adverse side effect of radiation therapy. Previous studies have demonstrated a lack of evidence to support common skincare advice for radiotherapy patients. The aim of the current study was to investigate the management of radiation‐induced skin toxicity across Europe and the USA. Where previous surveys have focused on national practice or treatment of specific sites, the current study aimed to gain a broader representation of skincare practice. An anonymous online survey investigating various aspects of radiotherapy skincare management was distributed to departments across Europe and the USA (n = 181/737 responded i.e. 25%). The UK was excluded as a similar survey was carried out in 2011. The results highlight the lack of consistency in both the prevention and management of radiation‐induced skin toxicity. Recommended products are often not based on evidence‐based practice. Examples include the continued use of aqueous cream and gentian violet, as well as the recommendations on washing restrictions during treatment. To our knowledge, this is the most extensive survey to date on the current management of radiation‐induced skin toxicity. This study highlights significant disparities between clinical practice and research‐based evidence published in recent systematic reviews and guidelines. Ongoing large prospective randomised trials are urgently needed.     

The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: a double-blind placebo-controlled prospective phase III study by Radiation Therapy Oncology Group 9901

PURPOSE: Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients. METHODS AND MATERIALS: Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 microg/m2 or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system. RESULTS: Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006). CONCLUSION: This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.     

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.     

The efficacy of erythropoietin mouthwash in prevention of oral mucositis in patients undergoing autologous hematopoietic SCT: a double‐blind,randomized, placebo‐controlled trial

Oral mucositis (OM) as a complication of high‐dose chemotherapy is frequently occurred in hematopoietic stem cell transplantation (HSCT) settings. Erythropoietin (EPO) has anti‐inflammatory, antioxidant and wound‐healing properties and therefore could have an important role in the prevention of OM. We conducted a double‐blind, randomized, placebo‐controlled trial to evaluate the EPO mouthwash effect on OM incidence and severity in 80 patients with non‐Hodgkin's lymphoma, Hodgkin disease (HD) or multiple myeloma, undergoing autologous hematopoietic stem cell transplantation. Patients received either EPO mouthwash (50 IU/ml, 15 ml four times a day) (n = 40) or placebo (n = 40) from the starting day of high‐dose chemotherapy until day +14 after transplantation or until the day of discharge from the hospital, whichever occurred first. OM was evaluated daily for 21 days after transplantation or until resolution of OM according to World Health Organization oral toxicity scale. The incidence of OM (grades 1–4) in the EPO mouthwash group and control group was significantly different (27.5% vs 77.5%, p < 0.001). The mean ± SD of two other parameters of OM including maximum intensity OM score (0.60 ± 1.06 vs 1.67 ± 1.27) and average intensity OM score (0.47 ± 0.80 vs 1.28 ± 0.86) was significantly lower in the intervention group (p < 0.001). Moreover, the mean ± SD duration of OM was also significantly shorter among the EPO mouthwash recipients (1.92 ± 3.42 days vs 5.42 ± 3.86 days, P < 0.001). Also, the duration of neutropenic fever was significantly shorter in the intervention group (2.12 ± 2.42 days vs 3.95 ± 4.01 days, p = 0.016). It is concluded that EPO mouthwash can reduce the incidence and duration of OM. Copyright © 2015 John Wiley & Sons, Ltd.