The use of low-energy laser (LEL) for the prevention of chemotherapy- and/or radiotherapy-induced oral mucositis in cancer patients: results from two prospective studies

Background  Low-energy laser (LEL) treatment has been suggested as an effective and safe method to prevent and/or treat oral mucositis induced by chemotherapy and/or radiotherapy; however, it has not gained wide acceptance so far. Materials and methods  We conducted two clinical trials testing the LEL technique: firstly, as a secondary prevention in patients with various solid tumors treated with chemotherapy who all developed severe mucositis after a previous identical chemotherapy and, secondly, as therapeutic intervention (compared to sham illumination in a randomized way) in patients with hematological tumors receiving intensive chemotherapy and having developed low-grade oral mucositis. Results  We entered 26 eligible patients in the first study and 36 were randomized in the second study. The success rate was 81% (95%CI = 61–93%) when LEL was given as a preventive treatment. In the second study, in patients with existing lesions, the therapeutic success rate was 83% (95%CI = 59–96%), which was significantly different from the success rate reached in the sham-treated patients (11%; 95%CI = 1–35%); the time to development of grade 3 mucositis was also significantly shorter in the sham-treated patients (p < 0.001). Conclusion  Our results strongly support the already available literature, suggesting that LEL is an effective and safe approach to prevent or treat oral mucositis resulting from cancer chemotherapy.     

Radiochemotherapy with amifostine cytoprotection for head and neck cancer

 A randomized study was conducted to evaluate the protective activity of amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT). Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week up to 60 Gy) with carboplatin 70 mg/m² on days 1–5 and 21–25 inclusive. Patients either received RCT alone (n=14) or RCT+A at a dose of 500 mg prior to treatment with carboplatin (n=25). There was a significant reduction in the incidence of grade 3/4 mucositis (P<0.0001), acute grade 2 xerostomia (P<0.0001) and grade 3/4 thrombocytopenia (P=0.012) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5% and 63.6% in patients who received RCT alone. There were 18 (72%) complete responses (CR) and 6 (24%) partial responses (PR) in patients who received A, compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The disease-free survival at 12 months is 85.7% in the RCT+A arm and 78.6% in the RCT alone arm. The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity.     

Monitoring Response to Radiotherapy in Human Squamous Cell Cancer Bearing Nude Mice: Comparison of 2′-deoxy-2′-[<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose (FDG) and 3′-[<Superscript>18</Superscript>F]fluoro-3′-deoxythymidine (FLT)

Objective The uptake of 3′-[¹⁸F]fluoro-3′-deoxythymidine (FLT), a proliferation marker, was measured before and during fractionated radiotherapy to evaluate the potential of FLT-positron emission tomography (PET) imaging as an indicator of tumor response compared to 2′-deoxy-2′-[¹⁸F]fluoro-d-glucose (FDG). Materials and Methods Nude mice bearing established human head and neck xenografts (HNX-OE; nu/nu mice) were locally irradiated (three fractions/week; 22 Gy) using a 150-kV_p unit. Multiple FDG- and FLT-PET scans were acquired during treatment. Tumor volume was determined regularly, and tissue was analyzed for biomarkers involved in tracer uptake. Results Both groups revealed a significant decline in tumor volume (P < 0.01) compared to untreated tumors. For FDG as well as for FLT, a significant decline in retention was observed at day 4. For FLT, most significant decline in retention was observed at day 12; whereas, for FDG, this was already noted at day 4. Maximum decline in tumor-to-nontumor ratios (T/NT) for FDG and FLT was 42 ± 18% and 49 ± 16% (mean ± SD), respectively. FLT uptake was higher then that of FDG. For FLT, statistical significant correlations were found for both tumor volume at baseline and at day 29 with T/NT and ΔT/NT. All tumors demonstrated expression of glucose transporter-1, thymidine kinase-1, and hexokinase II. No differences were found for amount of tumor cells and necrosis at the end of treatment. Conclusion This new experimental in vivo model supports the promise of using FLT-PET, as with FDG-PET, to monitor response to external radiotherapy. This warrants further clinical studies to compare these two tracers especially in cancers treated with radiotherapy.     

Prophylaxis with povidone-iodine against induction of oral mucositis by radiochemotherapy

Oral mucositis is a frequent complication of radiochemotherapy. The origin of radiation-induced mucosal lesions is iatrogenic in nature, although further development of mucositis is essentially influenced by infection. It can be assumed that disinfection measures should decrease the severity of mucositis induced by radiochemotherapy. Therefore, in a prospective randomised study the efficacy of prophylactic oral rinsing with a disinfection agent was investigated. A randomised, prospective comparative trial was conducted with 40 patients undergoing radiochemotherapy of the head and neck region because of malignant disease. The treatment scheme consisted of irradiation to the tumour region and adjacent lymph nodes, with a total dose of 71.3 Gy, and simultaneous chemotherapy with carboplatin (60 mg/m²) on days 1–5 and 29–34. In all patients mucositis prophylaxis with nystatin, rutosides, panthenol and immunoglobulin was undertaken. In addition, 20 patients rinsed the oral cavity 4 times daily with povidone-iodine solution, while the group for comparison rinsed with sterile water. Clinical examination of the oral mucosa was performed weekly. Onset, grading and duration of mucositis were used as the main variables. Clinically manifest oral mucositis was observed in 14 patients in the iodine group (mean grading: 1.0) and in all 20 patients in the control group (mean grading: 3.0). The total duration (mean) of clinically observed mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. Median AUC (area under curve for grade vs duration) was 2.5 in the iodine rinsing patients and 15.75 in control patients. All differences found between the two groups were statistically significant. Increased iodine incorporation was not observed. A pathologic rise in thyroid hormone levels was not found in the iodine group. The results obtained indicate that incidence, severity and duration of radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing with povidone-iodine in addition to the standard prophylaxis scheme. It can be concluded that rinsing with povidone-iodine is an easy, cheap and safe prophylactic method and can be recommended as a supportive treatment during antineoplastic treatment of the head and neck region.     

Effect of complementary and alternative medicine during radiotherapy on radiation toxicity

Goal of work To examine the frequency and types of complementary and alternative medicine use in patients undergoing radiotherapy and to analyze the effects these therapies have on the toxicities of radiotherapy. Materials and methods A total of 210 consecutive cancer patients undergoing radiation therapy were included. After radiation therapy, each patient completed a standard questionnaire, and the association between radiation toxicity and complementary and alternative medicine use was analyzed. Main results Among the study population, 44.3% of patients reported using at least one form of complementary and alternative medicine during radiotherapy. The most commonly chosen complementary and alternative medicine was stinging nettle. Complementary and alternative medicine use decreased lower gastrointestinal (F = 3.26, P = .009) and genitourinary toxicities (F = 2.38, P = .043), while it increased laryngeal toxicity (F = 2.63, P = .028). A significant correlation between the type of complementary and alternative medicine used and the degree of these toxicities was not demonstrated. Conclusions Use of complementary and alternative medicine among cancer patients during radiation therapy may affect the degree of radiation toxicity. Further randomized controlled clinical trials are needed to determine the benefits and risks of complementary and alternative medicine use during radiation therapy.     

Differential responses of fibroblasts,non-neoplastic epithelial cells,and oral carcinoma cells to low-level laser therapy

Low-level laser therapy (LLLT) is used in the treatment of chemoradiotherapy- or radiotherapy-induced oropharyngeal mucositis (ORM). In head and neck cancer, tumor cells may lie in the LLLT irradiation field, and LLLT might promote tumor progression. We therefore investigated the effect of LLLT on proliferation, cell cycle distribution, and apoptosis in a human oral carcinoma cell line (SCC-25), non-malignant epithelial cells (BEAS-2B), and fibroblasts in vitro. The cell lines were subjected to LLLT on three consecutive days for 15 min. Cell proliferation was assessed using the MTT assay, cell cycle distribution by flow cytometry and propidium-iodide DNA staining, and apoptosis using an Annexin V-FITC assay. Controls were sham-treated, but not exposed to the laser treatment. LLLT treatment resulted in increased fibroblast proliferation (p < 0.001), whereas decreased cell proliferation was observed after LLLT treatment of BEAS-2B (p = 0.003) and SCC-25 cells (p < 0.001). In SCC-25 cells, an increased percentage of S-phase cells and decreased percentage of G1-phase cells were observed (p < 0.001). Moreover, a proapoptotic effect of LLLT was observed in SCC-25 cells (p = 0.02). LLLT did not exhibit a tumor-promoting effect in this in vitro study.     

11C-Methionine-PET for Evaluation of Carbon Ion Radiotherapy in Patients with Pelvic Recurrence of Rectal Cancer

Purpose  Progress of the novel carbon ion radiotherapy (CIRT) in the treatment of cancers has created the need for a method to accurately evaluate the response. We investigated whether l-[¹¹C]methyl-methionine (¹¹C-methionine) uptake at pre- and post-CIRT could be an early response predictor in patients with pelvic recurrence of rectal cancer. Procedures   ¹¹C-Methionine-positron emission tomography (PET) was performed prospectively in 53 patients with pelvic recurrence of rectal cancer before CIRT, and 48 patients were performed ¹¹C-methionine PET at 1 month after CIRT. ¹¹C-Methionine tumor uptake was measured by the tumor to muscle ratio (T/M ratio). The T/M ratios were evaluated in relation to clinical outcomes such as local re-recurrence, distant metastasis, and survival. The response to CIRT was also judged by computed tomography (CT) and magnetic resonance imaging (MRI). ¹¹C-Methionine PET judgment was compared with CT/MRI judgment regarding the relevance to clinical outcome. Results  Baseline T/M ratio was 5.27 ± 1.90 (mean ± SD) in patients without developing local re-recurrence and 7.66 ± 3.17 in patients with local re-recurrence (p = 0.023, Mann–Whitney U test). Post-CIRT T/M ratios were 3.10 ± 1.28 in patients without local re-recurrence and 6.15 ± 2.98 in patients with local re-recurrence (p = 0.006, Mann–Whitney U test). By Kaplan–Meier analysis with log-rank test, patients with a baseline T/M ratio of ≦7.6 or a post-CIRT T/M ratio of ≦5.0 had significant lower pelvic re-recurrence rate. However, the percent change (reduction rate) from baseline to post-CIRT T/M ratio did not have significant relation to pelvic re-recurrence. There were no significant differences between ¹¹C-methionine results (baseline T/M ratio, post-CIRT T/M ratio and percent change) and other clinical parameters (distant metastasis and survival). Conclusion   ¹¹C-methionine-PET can be used for early prediction of local re-recurrence after CIRT. Because CIRT is local therapy, ¹¹C-methionine-PET cannot predict distant metastasis or survival after CIRT.     

Effect of oral nutritional supplementation on weight loss and percutaneous endoscopic gastrostomy tube rates in patients treated with radiotherapy for oropharyngeal carcinoma

Goals Malnutrition in the head and neck cancer population is a widely recognized factor contributing to negative outcomes. The goal of this study was to determine if providing complimentary oral nutritional supplementation for patients undergoing definitive radiation therapy for oropharyngeal carcinoma reduced weight loss and the need for percutaneous endoscopic gastrostomy (PEG) tube placement. Materials and methods The data from 79 patients undergoing radiotherapy for oropharyngeal cancer were extracted and analyzed retrospectively from an institutional Human Investigation Committee approved database for the study of advanced radiation therapy techniques for head and neck cancer. Forty patients were treated before the initiation of a nutritional supplementation program, and 39 patients received supplementation. Patients were stratified by type of treatment (radiation alone or chemoradiation) and whether or not they had a PEG tube. Results All patient groups receiving supplementation manifested a significant decrease in weight loss compared to those who did not receive it. Nutritional supplementation was associated with a 40% relative reduction in weight loss in patients treated with radiotherapy alone (6.1 vs 10.1%, p = 0.008) and a 37% reduction in weight loss in patients treated with chemoradiotherapy (6.7 vs 10.7%, p = 0.007). When patients were stratified by the presence or absence of a PEG tube, both groups experienced a 39% relative reduction in weight loss (with PEG, 5.7 vs 9.3%, p = 0.028; without PEG, 6.9 vs 11.2%, p = 0.002). Supplementation was associated with a decreased need for PEG tube placement (31% decreased to 6%) in patients treated with radiotherapy alone. Conclusions Providing complimentary oral nutritional supplementation significantly decreases weight loss and the need for PEG tube placement in patients undergoing radiation therapy for oropharyngeal cancer.     

Granisetron, tropisetron, and ondansetron in the prevention of acute emesis induced by a combination of cisplatin–Adriamycin and by high-dose ifosfamide delivered in multiple-day continuous infusions

 The antiemetic efficacy of granisetron, ondansetron and tropisetron was evaluated in patients treated with cisplatin–Adriamycin (CDP/ADM) and ifosfamide (IFO) by continuous infusion (CI). In all, 90 patients with osteosarcoma were randomly assigned to receive granisetron (2 mg/m²), or ondansetron (5.3 mg/m²), or tropisetron (3.3 mg/m²) plus dexamethasone 8 mg/m². Chemotherapy consisted of CDP (120 mg/m², 48-h CI) followed by ADM (75 mg/m², 24-h CI) and then, in the second cycle, delivered 3 weeks later, IFO 15 g/m² (120-h CI). Complete protection (CP) from emesis was obtained on 59% of the 717 days of treatment, without significant differences among the three study drugs. A significantly higher rate of CP was obtained during chemotherapy with IFO than with CDP/ADM (69% vs 44%; P<0.0001). The rate of CP declined from the first to the last day of treatment for both CDP/ADM (61% to 27%, P<0.0001) and IFO (95% to 43%) cycles (P<0.0001). When CDP/ADM and IFO are delivered on multiple days by CI, granisetron, ondansetron and tropisetron have the same antiemetic efficacy, which declines from the first day onward through successive days. Published online: 5 October 1999     

Efficacy of treatment to relieve mucositis-induced discomfort

 To determine the efficacy of a mouthwash in relieving mucositis-induced discomfort in patients receiving chemotherapy, 31 (16 male, 15 female) with a mean age of 45 (range 16–80) were given an in-house three-drug (lidocaine, diphenhydramine and sodium bicarbonate in normal saline) mouthwash when they developed mucositis of any severity. The complications were assessed on the CALGB (Cancer and Leukemia Group B) scale. The response to the mouthwash was reported on a self-assessment scale. Patients' response data were analyzed with reference to: (1) relief throughout the duration of mucositis and (2) relief during the worst stage (for each episode) of mucositis. Five patients with fungal, viral or bacterial oral infection were excluded from study. Overall, 4 patients had grade I, 16 patients had grade II, 10 patients had grade III and 1 patient had grade IV mucositis. The average duration of mucositis was 7.9 days (range 3–23 days), and the mean duration of the worst stage of mucositis was 4.81 days (range 2–13 days). The mean mucositis severity score was 1.9 (range 1–4), and the average self-assessment (response) score was 0.81 (range 0–2). The mean mucositis score during the worst stage of mucositis was 2.25 (range 1–4), and the average self-assessment (response) score during the worst stage of mucositis was 0.91 (range 0–2.7). These results suggests that this three-drug mouthwash provides effective symptomatic relief in patients with chemotherapy-induced mucositis. Published online: 5 October 1999     

Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy

 Lower hemibody radiotherapy is an effective palliative treatment for patients with widespread bone metastases, but is frequently associated with the unpleasant side effects of nausea and vomiting. Patients often require admission to hospital for at least an overnight stay, with its inevitable costs. This study has investigated the clinical efficacy and safety profile of ondansetron, a 5HT₃ receptor antagonist, and compared it to a standard antiemetic combination, chlorpromazine and dexamethasone. Sixty-six patients were randomised to receive antiemetic prophylaxis with either oral ondansetron or a combination of chlorpromazine and dexamethasone (33 patients in each arm): 60 were treated with lower abdominal radiotherapy (8 Gy mid-plane dose) and 6 with radiotherapy to the upper lumbar spine (12.5 Gy incident dose). Patients were assessed for severity of nausea and vomiting and for whether they would use the same antiemetic again. Quality of life was assessed using the Functional Living Index Cancer (FLIC) and Functional Living Index Emesis (FLIE) quality-of-life questionnaires. A detailed cost–benefit analysis was also performed. Ondansetron scored highly as an antiemetic, being significantly better at controlling emesis on all four study days (P<0.001) and significantly better at controlling nausea on day 1 (P<0.001) than the standard combination of chlorpromazine and dexamethasone. Quality of life was better in the ondansetron-treated group, and ondansetron was found to be safe with no significant adverse effects. As a result, 98% of patients and investigators would use ondansetron again. Cost–benefit analysis revealed that, when complete control of emesis is the aim, ondansetron is not unduly expensive compared to the standard antiemetic regimen. As ondansetron was clearly effective in patients receiving hemibody irradiation it seems it would be prudent to adopt it for use in such patients routinely. The use of ondansetron would allow them to be treated as outpatients, with the attendant financial and psychosocial benefits of such an approach.     

Safety and tolerability of velafermin (CG53135-05) in patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplant

Goals of work The objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis (OM) from chemotherapy. Materials and methods This study was a single-center, open-label, single-dose escalation, phase I trial in patients undergoing high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSCT). Velafermin was administered 24 h after stem cell infusion as a single intravenous dose infused over 15 min. Clinical safety variables were assessed and OM status scored daily for 30 days using the World Health Organization (WHO) grading scale. Main results Thirty patients were treated with velafermin at doses of 0.03 (n = 10), 0.1 (n = 10), 0.2 (n = 8), or 0.33 mg/kg (n = 2). Patients were diagnosed with multiple myeloma (n = 16), non-Hodgkin’s lymphoma (n = 12), acute myelogenous leukemia (n = 1), or desmoplasmic round cell tumor (n = 1). Velafermin was well tolerated at doses up to 0.2 mg/kg. There were no drug-related serious adverse events. No patient discontinued because of adverse events; however, two patients administered 0.33 mg/kg developed adverse reactions immediately after infusion of the study drug. No other patients were treated at this dose level. The most frequent (>35% of patients) treatment-emergent adverse events were diarrhea, fatigue, pyrexia, vomiting, and nausea. Most adverse events were mild or moderate and resolved the same day without sequelae. Eight (27%) patients developed WHO grade 3 or 4 OM during the study; seven of these patients received high-dose melphalan as a conditioning regimen. Conclusion Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2 mg/kg.     

Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity?

Background  Obesity is a well-known problem in children with acute lymphoblastic leukemia (ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with intermittent dexamethasone (DEXA). Methods  Body mass index (BMI), energy intake, and physical activity were measured in 16 ALL patients on maintenance treatment and in 17 healthy controls. ALL patients were measured during (“on DEXA”) and in between (“off DEXA”) DEXA treatments. Results  In patients, the mean increase in BMI z-score was 1.4 ± 1.1. Energy intake on DEXA was higher (2,125.9 ± 476.0 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05) and energy intake off DEXA was lower (1,305.0 ± 249.4 vs 1,775.1 ± 426.1 kcal/24 h, p < 0.05), compared to healthy controls. Physical activity on DEXA was lower compared to healthy controls (30.0 ± 3.9 vs 40.0 ± 6.0 kcal kg⁻¹ 24 h⁻¹, p < 0.001 and 7,303.1 ± 4,622.9 vs 13,927.2 ± 3,822.7 steps, p < 0.05). Physical activity off DEXA was not different compared to healthy controls. Conclusion  Weight gain in patients on ALL treatment might be owing to increased energy intake and decreased physical activity during treatment with DEXA.     

Herpes simplex virus-1 (HSV-1) infection in radiation-induced oral mucositis

Goal of work The aim of the study was to investigate the incidence of herpes simplex virus-1 (HSV-1) infection in mucositis during head and neck cancer radiotherapy.Patients and methods Sixty patients with malignant head and neck tumor, eligible to receive radiotherapy, who were referred to the Dental Oncology Unit, entered the study. Sixteen patients (26.6%) received concomitant chemotherapy. Mucositis was recorded weekly. Smears taken from the ulcers of mucositis grade 2, or 3, or 4 were stained with Papanicolaou and alkaline phosphatase/antialkaline phosphatase immunocytochemical method to identify HSV-1.Main results Forty-eight of all 60 patients developed ulcerative mucositis. Smear was available from 29 of 48 patients with ulcerations. HSV-1 infection was identified in 14 of 29 smears available (48.2%). Mucositis healed or was reduced after 1 week of antiviral treatment in 11 of those 14 HSV-1-positive patients; 3 patients responded to 1 g/day of valacyclovir, 7–2 g/day, and 1 patient responded to i.v. acyclovir. Ulcerations recurred after quitting antivirals. Three patients did not respond to 1 g/day of valacyclovir. No HSV-1-negative patient responded to acyclovir (P=0.000).Conclusion HSV-1 was isolated from 14 of 29 available smears taken from 48 patients with ulcerative mucositis. The incidence of HSV-1 infection during radiotherapy was estimated as being 14 of all 48 patients at risk (29.1%). Healing or reduction in the grade of mucositis after antivirals in HSV-1 positive patients, combined with the negative response to antivirals in HSV-1 negative patients, denoted that HSV-1 infection was a component of ulcerative radiation mucositis in those HSV-1-positive patients.     

Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients

Background

The aim of this study was to review the available literature and define clinical practice guidelines for the use of laser and other light therapies for the prevention and treatment of oral mucositis.

Methods

A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible.

Results

A new recommendation was made for low-level laser (wavelength at 650?nm, power of 40?mW, and each square centimeter treated with the required time to a tissue energy dose of 2?J/cm² (2?s/point)) for the prevention of oral mucositis in adult patients receiving hematopoietic stem cell transplantation conditioned with high-dose chemotherapy, with or without total body irradiation. A new suggestion was made for low-level laser (wavelength around 632.8?nm) for the prevention of oral mucositis in patients undergoing radiotherapy, without concomitant chemotherapy, for head and neck cancer. No guideline was possible in other populations and for other light sources due to insufficient evidence.

Conclusions

The increasing evidence in favor of low-level laser therapy allowed for the development of two new guidelines supporting this modality in the populations listed above. Evidence for other populations was also generally encouraging over a range of wavelengths and intensities. However, additional well-designed research is needed to evaluate the efficacy of laser and other light therapies in various cancer treatment settings.     

Quality of life of breast cancer patients in the course of adjuvant radiotherapy

Goals of the work In cancer patients, there is an ongoing interest in evaluating the impact of therapeutic interventions on health-related quality of life (hrqol). However, only a few longitudinal studies are published being able to measure the influence of therapy for the patients’ quality of life. Based on these data, our aim was to evaluate changes of hrqol during the course of adjuvant radiotherapy in breast cancer patients with special focus on subgroup analysis. Materials and methods Sixty-one women undergoing radiotherapy after breast conserving surgery were asked to answer the EORTC Quality of life questionnaire (EORTC-QOL-C30) three times: at the beginning of radiotherapy, in the forth week and 6 weeks after the end of treatment. To identify patients with changes of their qol during the observation time, the function scale “Global health status/Quality of life” was used enabling us to classify three subgroups: (1) unchanged hrqol (NC), (2) increasing hrqol (INC), (3) decreasing of hrqol (DEC). Main results Patients with an increasing hrqol (N = 25) demonstrated a significant increase in the role as well as in the emotional functioning scales. In patients with a decreasing hrqol (N = 15), no changes in any of the function scales were found, while a significant decrease in their cognitive functioning was observed in patients with no change in hrqol (N = 21). Conclusions Although the interpretation of these data is difficult because only a few data are available to compare our results, it could be demonstrated that emotional support and the ability to maintain a daily routine in additionally irradiated breast cancer patients is important to optimise hrqol. If hrqol decreases during the course of radiotherapy, the function scales of the EORTC-QOL-C30 seem to be insensitive to reflect this decrease.     

Role of the cyclooxygenase pathway in chemotherapy-induced oral mucositis: a pilot study

Goals  

Oral mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced oral mucositis.     

Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy

Goal of work The aim of the study is to evaluate the effect of fluconazole antifungal prophylaxis on the severity of mucositis in head and neck cancer patients receiving radiotherapy.Patients and methods Sixty-three patients, with malignant head and neck tumor, eligible to receive radiotherapy, entered the study. Thirty-four patients (group A) received 100 mg/day of fluconazole prophylaxis during radiotherapy and were compared with 29 patients, who received radiotherapy alone (group B). The two groups were similar in terms of patients and radiotherapy characteristics. Smear to test for Candida carriage was taken before and after radiotherapy. Oral candidiasis was diagnosed using the criteria described before. Oral mucositis was recorded according to EORTC/RTOG criteria.Main results A significant reduction of severe mucositis at the end of radiotherapy (14.7 vs 44.8%, p=0.018) and of interruptions (0 vs 17.2%, p=0.017) was observed in group A. Candidiasis was prevented (0 vs 34.5%, p=0.001), with a significant reduction of Candida carriage of 40.7% (p=0.001).Conclusion Fluconazole prophylaxis showed a significant beneficial impact on the severity of mucositis and on radiotherapy interruptions in this group of patients. The current study provides data on the build of a randomized controlled trial on the effect of fluconazole prophylaxis on treatment schedule and quality of life of the patients during head and neck radiotherapy.     

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

 There is still controversy as to what constitutes the optimal therapy for acute and delayed chemotherapy-induced emesis and nausea. We conducted a three-armed randomized multi-centre study in 193 chemotherapy-naive patients receiving highly emetogenic chemotherapy inducing both acute and delayed symptoms (cisplatin ≥50 mg/m², carboplatin ≥300 mg/m², cyclophosphamide ≥750 mg/m², ifosfamide ≥1.5 g/m² on day 1). Group A: 1×5 mg tropisetron i.v. on day 1+2, then 10 mg p.o. (oral dose now recommended: 5 mg); group B: tropisetron as for A+dexamethasone, 20 mg i.v., on days 1+2, then 4 mg i.v./p.o.; group C: tropisetron as for A+metoclopramide, 20 mg i.v.+2×10 mg p.o. on day 1, then 3×10 mg p.o. Treatment was continued for at least 2 days after the end of chemotherapy. Tropisetron+dexamethasone was significantly superior to tropisetron alone both for acute (P=0.0064) and delayed (P=0.0053) emesis. Complete control of acute and delayed emesis (nausea) was achieved in 80% (75%) and 53% (46%) in group A, 97% (90%) and 80% (58%) in group B, and 86% (80%) and 49% (45%) in group C. Patients completely asymptomatic during the whole cycle accounted for 26% of those in group A, 49% in group B and 28% in group C. The most frequent adverse events were constipation (16.6%), headache (7.3%) and tiredness (7.3%). Once-daily tropisetron+dexamethasone over several days is well tolerated and is a simple means of achieving further significant improvement in the efficacy of tropisetron against acute and delayed symptoms.     

Randomized, double-blind comparison of granisetron versus granisetron plus prednisolone as antiemetic prophylaxis during multiple-day cisplatin-based chemotherapy

 Ninety chemotherapy-naive cancer patients receiving cisplatin-based (≥50 mg/m²) chemotherapy participated in a randomized, double-blind, cross-over study comparing the safety and efficacy of granisetron (GRA) versus granisetron plus prednisolone (GRA+PRE). All patients received i.v. granisetron 3 mg and were randomly allocated to oral prednisolone 50 mg or placebo prior to chemotherapy. At the subsequent cycle of chemotherapy, patients were crossed over to the other antiemetic treatment. A complete response, defined as no eme- tic episodes and no worse than mild nausea, was obtained in 63% in the GRA group and in 79% of the patients in the GRA+PRE group day 1 (P=0.013). Complete response rates on days 1–3 were 16% vs 27% (P=0.251). Significantly less nausea and vomiting was seen with the combination in the first 24 h after cisplatin (P=0.001 and P=0.0003) and during days 1–3 (P=0.005 and 0.044). Patient preference was 51.5% for the combination and 26.5% for granisetron alone, whereas 22% had no preference (P=0.0270). Adverse reactions were mild and comparable; headache and constipation were the ones most frequently reported. Prednisolone significantly improves the antiemetic effect of granisetron in patients receiving cisplatin-based chemotherapy, but the study also emphasizes the poor complete protection rate in patients receiving multiple-day cisplatin-based chemotherapy.