Phillips, R.S., Friend, A.J., Gibson, F., Houghton, E., Gopaul, S., Craig, J.V., & Pizer, B. (2016). Antiemetic medication for prevention and treatment of chemotherapy-induced nausea and vomiting in childhood. Cochrane Database of Systematic Reviews, 2, CD007786.
STUDY PURPOSE: To update a previous systematic review regarding the effectiveness and adverse events of pharmacologic interventions used to control anticipatory, acute, and delayed nausea and vomiting in children younger than 18 years who are preparing to receive chemotherapy
TYPE OF STUDY: Meta-analysis and systematic review
PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Pediatrics
Thirty-four studies using a range of antiemetic regimens produced a variety of outcomes. The majority of quantitative data related to the complete control (CC) of acute vomiting (27 studies). Adverse events were reported in 29 studies and nausea outcomes in 16 studies. Two studies assessed the use of dexamethasone with 5-HT3 antagonists for CC of vomiting (pooled risk ratio [RR] = 2.03, 95% confidence interval [CI] [1.35, 3.04]). Three studies compared 20 mcg/kg granisetron with 40 mcg/kg for CC of vomiting (pooled RR = 0.93, 95% CI [0.8, 1.07]). Three studies compared granisetron and ondansetron for CC of acute nausea (pooled RR = 1.05, 95% CI [0.94, 1.17], two studies), acute vomiting (pooled RR = 2.26, 95% CI [2.04, 2.51], three studies), delayed nausea (pooled RR = 1.13, 95% CI [0.93, 1.38], two studies), and delayed vomiting (pooled RR = 1.13, 95% CI [0.98, 1.29], two studies). Narrative synthesis suggests that 5-HT3 antagonists are more effective than older antiemetic agents, even when these agents are combined with a steroid. Cannabinoids are probably effective but produce frequent side effects.
This review provides evidence that knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in pediatrics is incomplete and additional research is needed. This review also indicates that 5-HT3 antagonists are effective in patients receiving emetogenic chemotherapy and that granisetron or palonosetron may be better than ondansetron. Adding dexamethasone improves control of vomiting, although the risk-benefit profile of adjunctive steroid remains uncertain.
Overall, the evidence related to the treatment of chemotherapy-induced nausea and vomiting in pediatric populations receiving emetogenic chemotherapy is lacking and requires additional research, and 5-HT3 medications have been shown to be effective in small studies.
Phillips, R., Hancock, B., Graham, J., Bromham, N., Jin, H., & Berendse, S. (2012). Prevention and management of neutropenic sepsis in patients with cancer: Summary of NICE guidance. BMJ, 345, e5368.
The purpose of the article was to assess systemic reviews of best available evidence, including consideration of cost, management of neutropenic sepsis leading to avoidable deaths, and the lack of systems for urgent assessment and lack of institutional policies for managing neutropenic sepsis. Adults (aged 18 or older) with acute leukaemias, stem cell transplantations or solid tumors with expected neutropenia of 0.5 x 109/L or less post-chemotherapy were assessed.
This was an evidence-based guideline with a guideline summary process of development.
Inclusion criteria included adult patients receiving chemotherapy. Exclusion criteria included being younger than age 18 and a diagnosis of lymphoma.
The phase of care was active anti-tumor treatment
High-quality evidence based on systematic reviews/meta-analyses of randomized, controlled trials (RCTs), moderate quality evidence based on systematic reviews, experienced opinion of Guideline Development Group (GDG), and National Cancer Action Team referenced as experience and opinion sources. Low-level evidence includes observational studies.
High-quality evidence (systematic reviews/meta-analysies of RCTs):
Moderate quality evidence (systematic reviews):
Experienced opinion of Guideline Development Group (GDG):
Low level evidence (observational studies):
High-quality evidence exists for practice recommendations:
Phillips, R.S., Gopaul, S., Gibson, F., Houghton, E., Craig, J.V., Light, K., & Pizer, B. (2010). Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database of Systematic Reviews (Online), 9, CD007786.
To assess effectiveness, adverse events, and quality of life associated with pharmacologic interventions for control of anticipatory nausea and vomiting in children about to receive chemotherapy and for control of acute and delayed nausea and vomiting in children receiving chemotherapy
Databases searched were MEDLINE, Embase, LILACS, and Cochrane CENTRAL register of clinical trials to February or March 2008.
Search keywords included the specific names of all drugs used for nausea and vomiting, including cannabinoids. Extensive listing of terms and Medical Subject Heading (MeSH) terms were provided in appendices. Multiple terms were included for pediatric cases. MeSH Nausea, MeSH Vomiting and anticipatory vomiting, Cancer and associated terms, and Chemotherapy. Manual reference screening and author contact for further information also was used.
Studies were included in the review if they
Studies were excluded if they
Initial searching provided 844 references. Of these, 67 were identified for detailed screening. A final sample of 27 articles reporting on 28 trials was included. Evaluation included assessment of study quality and risk of bias.
A broad range of adverse events were reported for 5-HT3 RAs. Those reported most frequently were headache, sedation/somnolence, and abdominal pain. The main side effects reported with cannabinoids were drowsiness, dizziness, mood alteration, and increased appetite. Only a few studies reported side effects with metoclopramide or chlorpromazine.
This review concluded that knowledge of the most effective antiemetics to prevent chemotherapy induced nausea and vomiting in children is incomplete and imprecise. Nausea often was reported with different methods that were not validated. No information was available about delayed or anticipatory nausea. Conclusions from these trials were that 5-HT3 RAs appear to be more effective than older antiemetic agents, even when those agents are combined with steroids. Additionally, 5-HT3 RAs with dexamethasone were effective in patients who were to receive highly emetogenic chemotherapy, although the addition of steroids was unclear. Cannabinoids were found to probably be effective. Related side effects may be experienced as adverse by some patients but not others.
The following areas for research were identified.
Future research should incorporate the use of validated measures and examination of appropriate schedules and doses to deal with anticipatory and delayed symptoms.
Philip, J., Gold, M., Milner, A., Di Iulio, J., Miller, B., & Spruyt, O. (2006). A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer. Journal of Pain and Symptom Management, 32(6), 541–550.
The objective of the study was to determine if patients preferred oxygen or air following 15-minute administration of both. Another aim of the study was to identify other factors that might impact the experience of dyspnea and the response to oxygen.
The study compared the response to oxygen and air in hypoxic and nonhypoxic patients. Patients were randomized to receive either oxygen or air at 4 L via nasal canula for 15 minutes. At the completion of 15 minutes, dyspnea intensity ratings and oximetry were repeated. Patients then spent 30 minutes without gas. Repeat measures were performed with a crossover to the other gas for 15 minutes. Measure of symptom intensity and oximetry were repeated, then the blinded patient and investigator designated the preferred gas.
The study reported on a sample of 51 patients. Dyspnea was related to the cancer in 47 patients (92%). In 29 of the 47 patients, cancer was the sole cause of dyspnea. In the remaining patients, dyspnea causes were from cancer complications, such as pneumonia (five patients), and cancer treatment, such as radiation pneumonitis. Fifteen patients (29%) had unrelated dyspnea causes, including 11 patients with chronic obstructive pulmonary disease.
Patients were eligible if
Patients were excluded if they
The study was conducted in two centers in Australia. Patients were recruited from inpatient and outpatient units.
Randomized, double-blind, crossover study
Twenty-seven patients (53%) were randomized to the air first arm and 24 patients (47%) to the oxygen arm. No significant difference was seen in VAS score improvement between the two types of gases (p = 0.622). No significant difference was seen in percentage of verbal ratings of improvement after first gas (p = 0.888) and after the second gas (p= 0.767). A significant difference was seen between the two gas types in mean increase in oxygen saturation (p < 0.001, air = 0.94%, oxygen = 5.43%) No significant correlation was seen between VAS score and oxygen saturation. Twenty-one patients (41%) preferred oxygen, 15 (29%) preferred air, and 15 (29%) had no preference. No significant difference (p = 0.357) was seen in patient preference for air or oxygen. In the subgroup of 17 hypoxic patients, mean change in VAS score did not differ significantly between air and oxygen (p = 0.812, air = 15.4 mm, oxygen = 13.3 mm), but mean oxygen saturation levels increased significantly more for oxygen than for air (p = 0.005, air = 2.7%, oxygen = 10.7%).
On average, patients improved symptomatically with both air and oxygen, and no significant difference was seen between the treatments. The subgroup of 17 hypoxic patients overall did not demonstrate a significant difference between air and oxygen, despite having improved oxygen saturations when administered oxygen. No major or minor flaws were noted in the study design. The authors designated clinically significant response to oxygen to be a preference for oxygen chosen by 60% of patients. If clinically significant improvement occurred at lower increments, this study may not have been adequately powered.
Air was not considered a placebo in this trial, but in fact a placebo effect may have been associated with air administration. Another possible explanation is that no differential response to either air or oxygen may be a result of mechanoreceptos stimulated by any gas administration. Patients who were dyspneic upon exertion but not dyspneic at rest were not eligible to enter the study. Eligible patients had to record a dyspnea VAS score of at least 30 mm. There may have been a different preference and response to the gases for exertional dyspnea.
Accruing 50 patients with dyspnea to this study took five years, which underscores the clinical fragility of patients who experience dyspnea and the difficulty in conducting research in this population. This evidence contradicts the findings of Bruera et al. (1993), who demonstrated that oxygen is beneficial to and preferred by patients with hypoxia.
Phianmongkhol, Y., Thongubon, K., & Woottiluk, P. (2015). Effectiveness of cognitive behavioral therapy techniques for control of pain in lung cancer patients: An integrated review. Asian Pacific Journal of Cancer Prevention, 16, 6033–6038.
STUDY PURPOSE: To synthesize the evidence regarding effectiveness of cognitive behavioral techniques (CBT) for pain in patients with lung cancer
TYPE OF STUDY: Systematic review
PHASE OF CARE: Late effects and survivorship
APPLICATIONS: Palliative care
The review included two studies that involved such interventions as distraction and relaxation and imagery rather than true CBT-approach interventions. No conclusions were drawn due to the lack of substantial evidence.
Very limited evidence exists regarding effects of CBT-type interventions for pain among patients with lung cancer.
This review showed there is little evidence to determine effectiveness of CBT for pain in patients with lung cancer.
Pham, H. P., Rogoza, K., Stotler, B., Duffy, D., Parker-Jones, S., Ginzburg, Y., . . . Schwartz, J. (2012). Granulocyte transfusion therapy in pediatric patients after hematopoietic stem cell transplantation: a 5-year single tertiary care center experience. Journal of Pediatric Hematology/Oncology, 34, e332–e336.
To determine the efficacy of granulocyte transfusion in neutropenic pediatric patients after undergoing hematopoietic stem cell transplantation (HSCT).
A retrospective observational review analysis was performed on all pediatric HSCT recipients between January 2005 and and January 2010 in a single center.
This was a retrospective observational review.
Data were analyzed using Fisher exact test for binary outcomes and the 2-tailed t test for continuous outcomes.
One hundred fifty-three granulocyte transfusions were administered to 16 pediatric HSCT recipients. Patients had bacterial infections (69%), fungal infections (19%), and combined infections (12%). Concurrent infections, mostly bacterial (60%), occurred. One adverse reaction of pulmonary toxicity was reported. The ANC of the stimulated products was significantly higher compared with the unstimulated products; however, neither the average number of granulocytes transfused by weight nor the outcomes difference were noticed between groups.
Granulocyte transfusion is safe in neutropenic and infected pediatric patients after HSCT. There was no difference in the outcomes between the groups that received stimulated products and those that received unstimulated products.
Recruiting pediatric patients for a randomized, controlled trial continues to be challenging.
Pfeil, A.M., Allcott, K., Pettengell, R., von Minckwitz, G., Schwenkglenks, M., & Szabo, Z. (2015). Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: A systematic review. Supportive Care in Cancer, 23, 525–545.
TOTAL REFERENCES RETRIEVED: 731 full publications and 108 Congress abstracts; duplicates were removed, leaving 700 items
PHASE OF CARE: Active antitumor treatment
Pegfilgrastim did not consistently show better efficacy or effectiveness in all studies, but the vast majority showed better efficacy and effectiveness compared to daily G-CSF, no upfront pegfilgrastim, no G-CSF or placebo in regards to CIN, febrile neutropenia (FN), chemotherapy dose reductions/delays, antibiotic use, and neutropenia-related hospitalizations. It is suggested that pegfilgrastim has an acceptable safety profile with similar AEs between pegfilgrastim and filgrastim.
Pegfilgrastim is currently being widely used in clinical practice, showing similar efficacy/effectiveness with acceptable safety profiles.
Limitations include the quality of the underlying studies. Some studies did not report number of patients receiving primary prophylaxis versus secondary prophylaxis, which may have led to underestimation of effectiveness. Studies were not consistent in their definitions of FN and CIN. Combined measures of effect are missing in the analysis.
Further studies in broader patient populations are needed to confirm. This review adds to the body of evidence that shows mixed findings regarding the question of whether pegfilgrastim use achieves better patient outcomes than daily filgrastim. It is also unclear if either of these has better results for primary or secondary prophylaxis.
Peuckmann, V., Elsner, F., Krumm, N., Trottenberg, P., & Radbruch, L. (2010). Pharmacological treatments for fatigue associated with palliative care. Cochrane Database of Systematic Reviews, 11, CD006788.
To determine the efficacy of pharmacological treatment on nonspecific fatigue in palliative care, including patients with advanced cancer and other chronic conditions associated with fatigue.
Databases searched were EMBASE, PsychLit, CENTRAL, and MEDLINE. Reference lists of identified articles were reviewed for inclusion, and textbooks were handsearched. Conference proceedings of the American Society of Clinical Oncology (ASCO) from 2000 to 2008 and the 2005 meeting of the European Cancer Conference were included in the search.
An extensive listing of keywords and specific search methods per database are provided in the article.
Studies were included in the review if
Studies were excluded if they studied megestrol or focused on physiologic deficiencies, such as lack of hemoglobin and use of erythropoietin.
Initial searching provided 2,000 titles. Of those, 22 met the inclusion criteria. They included data from 11 drugs: amantadine (6), pemoline (3), methylphenidate (3), dexamphetamine (2), paroxetine (2), acetyl-L-carnitine (2), testosterone (2), fluoxetine (1), donepezil (1), modafinil (1), and acetylsalicylic acid (1). If two or more studies of the same medication could be analyzed in the same subpopulation of patients, meta-analysis was performed. Meta-analysis was performed for amantadine, pemoline, methylphenidate, and modafinil.
Most studies showed some beneficial effect; however, a substantial similar placebo effect was often observed.
Amantadine
Pemoline
Methylphenidate
Dextroamphetamine
Paroxetine
Testosterone
Acetyl-L-carnitine
Modafinil
Donepezil
Other
Methylphenidate and amantadine showed promise for reducing fatigue in patients with advanced disease. Amantadine has not been studied in patients with cancer-related fatigue, but it has been shown to be effective in patients with MS. The meta-analysis included only a few studies and the evidence was weak, pointing to the need for additional research in this area. It is not clear whether amantadine would be useful for patients with cancer, as this has not been studied.
The analysis was performed only in palliative care populations and did not include studies of methylphenidate in patients with cancer during active treatment, which also have shown some efficacy. However, side effects included insomnia, anorexia, behavior change, and vertigo in studies reviewed with methylphenidate. In addition, although statistically significant, effect sizes were small. These findings suggest that use in patients with cancer, who also may experience anorexia and sleep disorders from other causes, has potential benefits that would need to be balanced with potential adverse effects. Carnitine, acetylsalicylic acid, and modafinil have been used in a few studies with positive results. These drugs warrant additional investigation to confirm efficacy in different patient populations with fatigue.
Pettit, L., Sanghera, P., Glaholm, J., & Hartley, A. (2014). The use of MuGard™, Caphosol® and Episil® in patients undergoing chemoradiotherapy for squamous cell carcinoma of the head and neck. Journal of Radiotherapy in Practice, 13(2), 218–225.
To record mucositis and dysphagia toxicity and level of anesthesia for patients receiving MuGard, Caphosol, or Episil in comparison to standard care
Patients undergoing concurrent radiotherapy and chemotherapy for locally advanced head and neck cancer were audited for eight weeks during treatment. Patients were sequentially given either the standard oral care regimen of aspirin, glycerin, and sucralfate and Gelclair® or one of the other products. Patients were assessed weekly during four weeks of radiotherapy and for four weeks after completion. All patients received the same protocol approach for analgesia.
PHASE OF CARE: Active antitumor treatment
Observational
Common Terminology Criteria for Adverse Events v3
No differences were seen between groups in average grade of dysphagia or analgesia use. No differences were seen between those receiving radiotherapy with intensity-modulated radiation therapy or conformal radiotherapy.
This study had numerous design limitations and provides little supportive evidence for any of the approaches used for prevention and management of oral mucositis or associated pain.
Pettersson, A., Johansson, B., Persson, C., Berglund, A., & Turesson, I. (2012). Effects of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life: A randomized controlled trial in prostate cancer patients undergoing radiotherapy. Radiotherapy and Oncology, 103(3), 333–340.
To examine the effect of decreased intake of insoluble dietary fiber and lactose on acute gastrointestinal (GI) side effects and other aspects of health-related quality of life (QOL) in patients with localized prostate cancer receiving radiotherapy (either brachytherapy or proton therapy)
Patients in the intervention group were instructed to avoid foods high in insoluble dietary fiber and lactose and to consume foods higher in soluble fibers and low in lactose beginning at baseline and continuing for 24 months past the completion of radiotherapy. Patients in the standard care group were instructed to continue their normal diet during this time period. Data was collected at four time points: prior to randomization and initiation of radiotherapy, after four weeks of treatment, one week after radiotherapy completion, and two months after completion of radiotherapy.
This was a single-site, outpatient study conducted in Uppsala, Sweden.
Patients were undergoing multiple phases of care.
This was a randomized controlled trial.
Both the intervention group and the standard care groups followed dietary instructions as indicated by an interaction effect between randomization and time in the FFQ scores (p ˂ 0.001). The dietary intervention had no statistically significant effect on GI side effects or other aspects of QOL, although bowel symptoms were lower in the intervention group.
The dietary intervention of decreased intake of insoluble dietary fibers and lactose did not have an effect on acute GI side effects in patients with localized prostate cancer undergoing radiotherapy (either brachytherapy or proton therapy).
Although this study did not show that a diet with reduced intake of insoluble dietary fiber and lactose had a significant effect on GI side effects, it did show a tendency toward lower prevalence of bowel symptoms in the intervention group during radiotherapy, which suggests the intervention may have had a positive effect. Controlling for health status in future studies might lead to a different outcome. Also, patients in this study had localized prostate cancer where a small part of the rectum was in the field of irradiation. Future research should evaluate the effect of the diet intervention in patients with lymph node positive disease, which would involve a larger bowel volume in the radiation field and increase the possibility of GI toxicity.