Low-energy He/Ne laser in the prevention of radiation-induced mucositis

 Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t (s)=energy (J/cm²)×surface (cm²)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2–7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy. Published online: 28 May 1999     

Unguided Clinical and Actuarial Assessment of Re-offending Risk: A Direct Comparison with Sex Offenders in Denmark

Meta-analyses suggest that actuarial risk assessments outperform unguided clinical judgment for prediction of recidivism in criminal offenders. However, there is a lack of direct comparisons of the predictive accuracy of clinical judgment and actuarial risk scales for sexual offenders. We followed up 121 male sex offenders (≥18 years) subjected to pre-trial forensic psychiatric assessment in Denmark in 1978–1992 (mean post-detainment time = 16.4 years) to compare the predictive validity of unstructured clinical judgment of recidivism risk with that of the well-established Static-99 (Hanson and Thornton, Law and Human Behavior 24:119–136, 2000) and an extension of the Static-99, the Static-2002 (Hanson and Thornton, Notes on the development of Static-2002 (Rep. No. 2003–01), Public Safety and Emergency Preparedness Canada, Ottawa, Canada, 2003). The predictive accuracy of unguided judgment did not exceed chance for any sexual, severe sexual or any violent (sexual or non-sexual) reconviction (AUCs of the ROC curve = 0.52, 95%CI = 0.41–0.63; 0.50, 95%CI = 0.34–0.67; and 0.57, 95%CI = 0.40–0.73, respectively). In contrast, all three outcomes were predicted significantly better than chance by the Static-99 (AUC = 0.62, 95%CI = 0.52–0.72; 0.72, 95%CI = 0.59–0.84; and 0.71, 95%CI = 0.56–0.86) and the Static-2002 (AUC = 0.67, 95%CI = 0.57–0.77; 0.69, 95%CI = 0.56–0.83; and 0.70, 95%CI = 0.55–0.86). Static-99 outperformed clinical judgment for sexual recidivision (χ² = 5.11, df = 1, p < .05). The Static-2002 was significantly more accurate for the prediction of any sexual recidivism as compared to unguided clinical judgment but its advantage fell just short of statistical significance for severe sexual recidivism (χ ² = 3.56, df = 1, p = 0.06). When tested for recidivism within 2 years, none of the three prediction methods yielded results significantly better than chance for any outcome. This direct trial of the unguided clinical method argues against its continued use for risk assessment of sexual offenders.     

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     

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.     

Health behaviors of Australian colorectal cancer survivors,compared with noncancer population controls

Goal  A better understanding of health behaviors after a cancer diagnosis is important, as these behaviors are related to physical functioning, disease recurrence, development of second primary cancers, and risk of other chronic diseases. Body weight and health behaviors (smoking status, alcohol consumption, and physical activity) were examined in a population-based sample of colorectal cancer survivors and compared to a matched population group. Materials and methods  Data were collected by telephone interviews pre-diagnosis (retrospectively reported), 6 and 12 months post-diagnosis for colorectal cancer survivors (n = 1,250). Comparison data were from a population-based cancer risk survey (n = 6,277). Results  Colorectal cancer survivors were most likely to be overweight/obese pre-diagnosis (66%) than at 6 months (54%) or 12 months post-diagnosis (61%). There was little variation from 6 to 12 months in the proportion of current smokers (7% and 8%, respectively) or high-risk drinkers (both 22%). The greatest changes were for physical activity, with 53% of survivor’s sufficiently active pre-diagnosis, 32% at 6 months, and 38% at 12 months post-diagnosis. At 12 months, colorectal cancer survivors were more likely than the comparison group to be: underweight (OR = 2.14, 95% CI = 1.38–3.31); a former smoker (OR = 1.44, 95% CI = 1.26–1.63); a low-risk (OR = 1.25, 95% CI = 1.09–1.44) or high-risk drinker (OR = 1.70, 95% CI = 1.43–2.03); and insufficiently active (OR = 1.57, 95% CI = 1.34–1.83) or inactive (OR = 2.76, 95% CI = 2.39–3.19). However, colorectal cancer survivors were significantly less likely to be a current smoker (OR = 0.68, 95% CI = 0.54–0.85). Conclusions  Our findings show particular scope for physical activity interventions for colorectal cancer survivors. Improving the general health of cancer survivors should help to decrease morbidity in this population and associated health system expenditure.     

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.     

Indicators of surgery and survival in oncology inpatients requiring surgical evaluation for palliation

Background  We sought to determine the clinical presentation, management, and outcomes associated with surgical consultation for symptom palliation in oncology inpatients. Materials and methods  We reviewed the medical records of inpatients for whom surgical consultations were requested (January 2000 to September 2006) at a tertiary referral cancer center to identify those who underwent surgical palliative evaluation (defined as consultation for symptoms attributable to an advanced or incurable malignancy). We used the Cox proportional hazards model to identify prognostic factors associated with overall survival (OS) and logistic regression to identify factors associated with surgical intervention. Results  Surgical consultation was requested for 1,102 inpatients; 442 (40%) met the criteria for surgical palliative evaluation. Gastrointestinal obstruction was the most common complaint (43%), while wound complications/infection and gastrointestinal bleeding accounted for 10% and 8%, respectively. The median OS was 2.9 months. Adverse prognostic factors for OS included ≥2 radiologically evident disease sites (HR = 1.4; 95% CI, 1.1–1.8) and carcinomatosis/sarcomatosis (HR = 1.4; 95% CI, 1.1–1.7). Palliative surgical procedures were performed in 119 (27%) patients, with a 90-day morbidity and mortality rate of 40% and 7% respectively. Patients with wound complications (OR = 3.3; 95% CI, 1.4–7.6), intestinal obstruction (OR = 1.9; 95% CI, 1.1–3.2), or an intact primary/recurrent tumor (OR = 3.6; 95% CI, 2.2–6.0) were more likely to undergo surgical intervention. Patients with ascites were less likely to undergo surgery (OR = 0.4; 95% CI, 0.2–0.8). Conclusions  Surgical palliative evaluations accounted for 40% of inpatient surgical consultations. Given that OS in this population is short and surgery is associated with considerable morbidity and mortality, non-operative management is desirable. Presented at the Supportive Care in Cancer MASCC/ISOO 2008 International Symposium in Houston, Texas on June 26–28, 2008.     

Oral ondansetron is highly active as rescue antiemetic treatment for moderately emetogenic chemotherapy: results of a randomized phase II study

Aims  In the present phase II randomized study, two different schedules of ondansetron were investigated as rescue antiemetic treatment for delayed emesis related to moderately emetogenic chemotherapy (MEC). Materials and methods  Patients scheduled to receive a first course of MEC were randomized to ondansetron 8 mg intramuscularly (arm A) or ondansetron 16 mg orally (arm B) as rescue antiemetic treatment for delayed emesis. Efficacy and safety evaluation was performed from days 2 to 6 through the administration of a diary plus a questionnaire in which the emetic episodes and the use of the assigned rescue treatment were recorded. All patients received standard prophylaxis for delayed emesis with oral dexamethasone 8 mg daily for 4 days starting on day 2. Results  Eighty-nine patients were enrolled into the study, of whom 44 were randomized to arm A and 45 to arm B. Twenty-two patients in each arm developed grade 1–2 delayed nausea/vomiting, all of which recurred to the rescue study treatment. Oral ondansetron resulted superior to intramuscular ondansetron in terms of complete response for nausea (77.3% vs 40.9%, respectively, p = 0.01) and vomiting (81.8% vs 31.8%, respectively, p = 0.001). Both schedules resulted to be very well tolerated, and no differences in toxicity were observed between the two arms of treatment. Furthermore, personal satisfaction about the use of the assigned rescue study medication was significantly higher in arm B. Conclusions  Due to its high efficacy and excellent tolerability, oral ondansetron is an important option in the management of MEC-related delayed emesis refractory to standard antiemetic prophylaxis.     

Randomized,double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

Purpose To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. Materials and methods 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m²/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1–5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2–6. Results Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1–5, days 6–9 and days 1–9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1–9 (P = 0.029). During the entire period (days 1–9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. Conclusion Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin₁ receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.     

Scalp cooling to prevent chemotherapy-induced hair loss: practical and clinical considerations

Objective  The objective of this prospective multicenter study was to obtain insight into the severity and burden of hair loss among cancer patients treated with chemotherapy. In addition, we described the effectiveness and burden of scalp cooling and the satisfaction with wigs, with hair regrowth, and with body image. Materials and methods  Breast cancer patients treated with (n = 98) and without (n = 168) scalp cooling completed questionnaires before chemotherapy and 3 weeks and 6 months after completion of chemotherapy. Results  Scalp cooling was effective in preventing chemotherapy-induced hair loss in 32 of 62 available patients (52%). Even though patients knew hair loss was temporary, it was a burden to 54% of them (n = 100). Scalp cooling was a burden for only 17 out of 51 patients (33%). Most patients who used a wig or head cover were satisfied with it (82%, n = 126). Patients were moderately satisfied with the regrowth of their hair after chemotherapy (mean 11.6; SD 2.53; range 0–20). Successfully cooled patients rated their hair as less important for their body image compared to patients who did experience hair loss (p = 0.014). Discussion  Chemotherapy-induced hair loss is perceived as burdensome. It may be prevented by offering scalp cooling which is often an effective method to prevent this form of hair loss and is tolerated well by patients. However, if possible, scalp-cooling techniques should be improved and their effectiveness should be increased because if scalp cooling is unsuccessful, patients’ rate their hair loss as more burdensome compared to noncooled patients. Mols and Hurk contributed equally to this work.     

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.     

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.     

Continued survival gains in recent years among critically ill myeloma patients

Objective  Therapeutic advances have improved survival in patients with myeloma (MM) over the past decade. We investigated whether survival has also improved in critically ill myeloma patients. Design  Retrospective study. Setting  Intensive care unit. Patient  Consecutive myeloma patients admitted to a teaching hospital ICU between 1990 and 2006. We compared three year-of-admission groups (1990–1995, 1996–2001, and 2002–2006) that matched changes in myeloma treatment (chemotherapy only, stem cell transplantation, and new molecules, respectively). Intervention  None. Measurements and main results  We included 196 patients. Reasons for ICU admission and patient characteristics were similar across groups; however, less use of conventional chemotherapy and radiotherapy and greater use of steroids were noted in the more recent periods. Over time, vasopressors and invasive mechanical ventilation were used decreasingly, and noninvasive ventilation increasingly, to treat acute respiratory failure. Hospital mortality decreased from 75% in 1990–1995 to 49% in 1996–2001 and 40% in 2002–2006 (P = 0.0007). Mortality was associated with poor performance status [OR 2.27, 95% CI (1.04–4.99)], need for mechanical ventilation [OR 4.33, 95% CI (1.86–10.10)], need for vasopressors [OR 2.57, 95% CI (1.12–5.86)], and admission for an event related to myeloma progression [OR 2.77, 95% CI (1.13–6.79)]. ICU admission within 48 h after hospital admission was associated with lower mortality [OR 0.28, 95% CI (0.19–0.89)]. Conclusion  Hospital mortality decreased significantly over the last 15 years in myeloma patients admitted to the ICU. Risk factors for death were organ failure and poor chronic health status. Early ICU admission was associated with lower mortality, suggesting opportunities for further improving survival.     

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.     

Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide

Goals of work  To assess the efficacy of adding aprepitant to a 5-HT₃ antagonist and dexamethasone as salvage antiemetic therapy for breast cancer patients receiving their initial cycle of an anthracycline and cyclophosphamide (AC) and failing to achieve complete control of emesis. Materials and methods  Eligibility: breast cancer patients receiving their first cycle of AC. Treatment: standard dose of a 5-HT₃ antagonist and dexamethasone 8–10 mg IV/PO on day 1 prior to cycle 1 of AC and dexamethasone 4 mg bid on days 2 and 3. Patients without complete control (no emesis, no nausea, or rescue antiemetics) during cycle 1 could proceed to cycle 2. During cycle 2, patients received AC and identical antiemetics (except dexamethasone 4 mg qd on days 2 and 3) plus aprepitant 125 mg PO day 1 and 80 mg PO days 2 and 3. Primary endpoint: complete control, 0–120 h after chemotherapy. Results  Sixty-two patients received cycle 1 of AC. Complete control cycle 1: 13 patients (21%; 95%CI, 12–33%). Of the 49 patients eligible for cycle 2, four elected not to continue on study. Of the 45 patients receiving cycle 2, 44 were evaluable. Complete control and complete response (no emesis, no rescue) for the 5-day study period improved from 0% to 18% (p = 0.14) and 7% to 36% (p = 0.02) on cycles 1 and 2, respectively. Conclusions  In breast cancer patients receiving AC, the addition of aprepitant to a 5-HT₃ antagonist and dexamethasone during cycle 2 of treatment improved antiemetic outcome. Although the improvement in the primary endpoint of complete control during cycle 2 was not significant, all secondary endpoints such as complete response and no emesis rates were significantly better during cycle 2. The extent of antiemetic control during cycle 2 was numerically inferior to the results achieved in a phase III trial employing aprepitant with cycle 1 of AC chemotherapy, suggesting that the preferred approach is to include aprepitant with the initial cycle of AC chemotherapy. Brian Trainor is already deceased.     

Sage tea–thyme–peppermint hydrosol oral rinse reduces chemotherapy-induced oral mucositis: A randomized controlled pilot study

ObjectiveThis pilot study aimed to investigate the preventive effect of sage tea–thyme–peppermint hydrosol oral rinse used in conjunction with basic oral care on chemotherapy-induced oral mucositis.DesignAn open-label randomized controlled study.SettingTwo oncology hospitals in Ankara, Turkey.InterventionsPatients receiving 5-fluorouracil-based chemotherapy regimens were divided into the intervention group (N = 30) and control group (N = 30). Basic oral care was prescribed to the control group, while the intervention group was prescribed sage tea–thyme–peppermint hydrosol in addition to basic oral care. All patients were called to assess their compliance with the study instructions on day 5 and 14.Main outcome measuresOral mucositis was evaluated using an inspection method or by assessing oral cavity photos based on the World Health Organization oral toxicity scale on day 5 and 14.ResultsMost of the patients in the intervention group did not develop oral mucositis on day 5. In addition, the incidence of grade 1 oral mucositis was statistically lower in the intervention group (10%) than the control group (53.3%) on day 5. By day 14, the majority of patients in both the groups had grade 0 oral mucositis.ConclusionsSage tea–thyme–peppermint hydrosol oral rinse has promising results in alleviating oral mucositis. This hydrosol can be recommended for clinical use as it is well tolerated and cost-effective. However, further randomized controlled trials are needed to support the study.     

154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial

To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders. We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints. We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601–2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI − 0.2–30.4%, p = 0.05). In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.     

Management of febrile neutropenia in solid tumours and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice

Goals of work Febrile neutropenia (FN) represents a spectrum of severity in which low-risk patients can be defined using the Multinational Association for Supportive Care in Cancer (MASCC) risk index. However, despite publication in 2000, there remains limited published literature to date to support the use of MASCC risk assessment in routine clinical practice and eligibility for early hospital discharge. In this study, we present our experience with the routine use of the MASCC risk index to determine the management of FN in our institution. Patients and methods Patients treated for solid tumours or lymphomas with low-risk FN (MASCC score ≥21) were eligible for oral antibiotics (ciprofloxacin plus either co-amoxiclav or doxycycline) and for early hospital discharge irrespective of first or subsequent episode. The primary outcome was rate of resolution of FN without serious medical complications (SMC). Secondary outcomes were the “success” of antibiotic therapy without treatment modifications, duration of hospitalisation and rate of readmissions. Results A total of 100 FN episodes occurring in 83 patients were treated over a 6-month period. Ninety of these episodes were low-risk (90%), of which 75 received oral antibiotics (83.3%) and 3 (3.3%) experienced SMC, and the success rate was 94.5% [95% confidence interval (CI) 89.6–99.3%] in low-risk episodes. The median duration of hospitalisation was 2.5 days (25th centile: 1.0 day; 75th centile: 5.0 days) in low-risk compared to 6.5 days (25th centile: 5.3 days; 75th centile: 9.3 days) in high-risk episodes (p = 0.003); 2 days for low-risk episodes treated with oral antibiotics compared to 4 days for low-risk receiving intravenous antibiotics (p = 0.015). Positive predictive value for the MASCC index was 96.7% (95% CI 95.0–98.6%). Conclusion The MASCC risk index is both feasible and safe when used in standard clinical practice to guide the management of FN in patients with solid tumours and lymphomas. Patients predicted to have low risk can be managed safely with oral antibiotics and early hospital discharge.