To evaluate the safety and efficacy of aprepitant, dexamethasone, and palonosetron as an antiemetic regimen for prevention of acute and delayed nausea and vomiting

Patients received one oral dose of 285 mg aprepitant and 20 mg dexamethasone one hour prior to cyclophosphamide and/or doxorubicin chemotherapy and 25 mg IV palonosetron 30 minutes prior to chemotherapy. Patients completed study diaries prior to the start of the single-day chemotherapy and then daily for five days.

• The sample consisted of 41 participants.
• Median age was 51, with a range of 33–74 years.
• Forty of the patients were female (97.5%), and one was male (2.5%). 
• Patients were diagnosed with solid tumors (no other information provided). The majority (n = 41) had performance statuses of 0 or 1.
• All patients received cyclophosphamide; 90% received doxorubicin and cyclophosphamide combination therapy.
• Patients could not receive corticosteroids or antiemetic agents other than the study drug doses immediately before or during the study period.

The study was conducted at multiple outpatient settings in Vermont and Maine.

All patients were in active treatment.

The study was a prospective trial.

• Patients recorded frequency and intensity of nausea and vomiting in study diaries.
• Nausea and vomiting was also measured based on the use of rescue antiemetic medication.

• Overall
  • 51% had a complete response (no vomiting and no rescue therapy)
  • 95% had no emesis
  • 32% had no nausea
• Acute phase (0–24 hours post chemotherapy)
  • 76% had complete response
  • 100% had no emesis
  • 59% had no nausea
• Delayed phase (24–100 hours post chemotherapy)
  • 66% had complete response
  • 95% had no emesis
  • 41% had no nausea
• Only 27% of patients had more than 1 day of significant nausea.
• No major adverse effects from medications were noted.

The single-day, three-drug (aprepitant, dexamethasone, palonosetron) antiemetic regimen is a safe and effective antiemetic regimen for patients receiving mildly or minimally emetogenic chemotherapy.

• No control group or comparison was provided.
• Only patients with low potential for nausea and vomiting were included in the study.
• Potential for bias exists, as patients may have underestimated their symptoms or rescue medications because they were a part of a study.

Identifying effective single-day antiemetic regimens may improve adherence to supportive care guidelines and reduce nausea and vomiting symptoms in patients receiving chemotherapy.

To investigate the effect of a single low dose (600 mg) of preoperative oral gabapentin on morphine consumption after total mastectomy and axillary dissection; to determine if the specified administration of gabapentin is safe 

Before total mastectomy and axillary dissection, patients received 600 mg gabapentin or placebo. Pain, sedation, nausea, vomiting, and side effects were monitored every 30 minutes for 2 hours and then every 2 hours until 12 hours after surgery.

• The sample was composed of 46 patients.
• The age range of patients was 18–75 years. In the placebo group, mean patient age was 44.9 years. In the gabapentin group, mean patient age was 46.6 years. 
• All patients were female. All patients were undergoing total mastectomy with axillary dissection ASA I or II.

• Single setting
• Inpatient
• Postanesthesia care unit

Randomized double-blind placebo-controlled trial

• 100-point pain rating scale
• Observer’s assessment of alertness or sedation
• Reports of nausea and number of episodes of vomiting

• Postoperative morphine consumption was 48% lower in the gabapentin group than in the placebo group (P < 0.001). 
• Compared to patients who received gabapentin, patients who received placebo had significantly higher postoperative pain scores and shorter times to rescue dose (P < 0.001).
• Authors noted no difference between groups in regard to sedation, incidence of nausea, and other side effects.

Pre-emptive administration of a single oral dose of gabapentin, 600 mg, led to a decrease in the use of postoperative analgesic.

• The study had a small sample size, with fewer than 100 patients.
• The study involved only one dose of gabapentin at a single time.
• The study followed patients for only 12 hours after surgery.

The use of preoperative gabapentin was associated with improved pain control and quality of life, without excessive side effects.

The purpose of the study was to determine whether calcium and magnesium infusions would prevent or ameliorate neurotoxity associated with oxaliplatin, enable a larger cumulative oxaliplatin dose delivered, ameliorate acute neuropathy associated with oxaliplatin, and whether any adverse events occurred.

Patients were randomly assigned to receive either IV calcium gluconate plus magnesium sulfate, 1 g each in 100 ml D5W for 30 minutes immediately before and after each dose of oxaliplatin, or an identical-looking placebo. Patients underwent a physical examination at study entry and before each two-week chemotherapy cycle, including an assessment for adverse events and toxicity as well as laboratory testing. Patients completed daily questionnaires before each dose of FOLFOX and for five days after completion of each cycle.

• The total sample consisted of 102 participants with a majority being men (53%) and older than age 65 (64%).
• All participants had stage II or III adenocarcinoma of the colon and were scheduled to receive six months of oxaliplatin-based FOLFOX chemotherapy.
• Exclusion criteria included a preexisting peripheral neuropathy of any grade, hypercalcemia, and having received prior neurotoxic chemotherapy.

The study was conducted in multiple outpatient settings throughout the United States.

• Active treatment
• Late effects

The study was a double-blind, placebo-controlled randomized clinical trial.

• The National Cancer Institute's Common Terminology Criteria for Adverse Events, verion 3.0
• A patient questionnaire using a 0–10 scale for sensitivity, discomfort swallowing, and muscle cramps.
• The North Central Cancer Treatment Group patient-reported outcome questionnaire to detect onset of neurotoxicity symptoms.

The study accrual was stopped before the original goal because of a data monitoring committee report regarding a similar trial in patients receiving palliative FOLFOX treatment in which interim analysis showed lower response rates in patients receiving calcium and magnesium. However, subsequent independent analysis of the data showed that initial interpretations were incorrect and that antitumor response was lower in that study's placebo group.

Results of the current study showed that the incidence of grade 2 or higher sensory neurotoxicity was significantly lower in the calcium and magnesium group on two different measurement scales (p < 0.04). In addition, onset of grade 2 or higher was significantly delayed in patients who received calcium and magnesium (p = 0.03). Patient report of numbness also was lower in the calcium and magnesium group (p = 0.021). The study intervention did not appear to have an effect of oxaliplatin-specific symptoms such as muscle cramps, throat discomfort, and cold sensitivity toxicities. No patients developed hypercalcemia.

The findings provide some support for the hypothesis that calcium and magnesium infusions can decrease oxaliplatin-related cumulative sensory neurotoxicity. The results suggest that some types of neurotoxic effects may be reduced, while no obvious effect on other symptoms is apparent.

• The study may have been underpowered because of premature closure to subject accrual.
• No information is provided regarding whether or not there were any FOLFOX dose reductions or discontinuations that also may have affected study findings.
• The authors stated that this was because of early study closure; however, why this would prevent providing any such data is unclear.

Calcium and magnesium infusion may reduce neurotoxicity associated with chemotherapy agents. Additional research in this area is needed to determine if both elements are required and what is the most effective dosages, timing, and efficacy with agents other than oxaliplatin. Research would further clarify the role of this intervention with specific neuropathic symptoms and whether this intervention is effective with various chemotherapeutic agents.

To compare effects of a mindfulness-based intervention to those of a psychoeducational telephone consultation on quality of life, depression, fatigue, and anxiety.

The study was begun as a randomized, controlled trial and patients were allocated at random to either the mindfulness-based or psychoeducational groups. Because of patient complaints about group assignment, in the second half of the study, patients were allocated to the group of their choice. The mindfulness intervention was based on mindfulness-based stress reduction concepts and activities and was provided in 2.5-hour group sessions weekly for eight weeks. They also had homework assignments, two 2.5-hour booster sessions at the end of 1 and 2 months during a three-month follow-up phase, and an all-day retreat. At baseline, individuals were interviewed to establish individual goals and, at the end of the program, were interviewed regarding goal attainment, maintenance of acquired skills, and evaluation of personal experience. The comparison group received 15-30 minutes of psychoeducational consultations by telephone twice a month for eight weeks. During the follow-up period, they had additional phone calls at the end of months 1 and 2. Study measures were obtained two weeks before and after the initial intervention and three months postintervention. Consultation with intervention teachers was used to evaluate treatment fidelity.

• N = 62, with 53 completers
• MEAN AGE = 52.1 (SD = 14.1)
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Patients were at least six months after completion of HCT and in complete remission at the time of enrollment. The mean time since transplantation was 7.5 years. All had hemotologic disease

• SITE: Not stated/unknown  
• SETTING TYPE: Not specified  
• LOCATION: Switzerland

• PHASE OF CARE: Late effects and survivorship

• Quasi-experimental phase and RCT phase

• Profile of Health Related Quality of Life in Chronic Disorders
• FACT scale
• CESD scale
• Fatigue questionnaire
• FACIT fatigue scale
• Spielberger State Trait Anxiety scale
• Goal Attainment assess on 11-point scale from -5 (completely unmet) to 5 (beyond expectation)

Quality of life and depression improved immediately after the intervention (p < 0.02)  At the three-month follow-up, significant differences were noted between groups, with improved quality of life in the mindfulness group (p = 0.04)  and lower depressive symptoms  and anxiety in the psychoed group (p = 0.04). There was no significant effect of either intervention on fatigue. There were no differences in outcomes based on whether the patient was randomly assigned or chose the preferred intervention.

Findings suggest that a mindfulness-based intervention may have positive benefits for overall quality of life and depressive symptoms in the short term, but this study did not show a long-term impact on depression or anxiety. No effect was seen for fatigue.

• Small sample (less than 100)
• Subject withdrawals of 10% or greater 
• Other limitations/explanation: 14.5% attrition in the mindfulness group and 7% in the comparison group. Booster sessions were only attended 50% of the time.

Findings suggest that a group mindfulness-based program for HCT survivors is feasible, although the overall attrition and poor attendance at follow-up sessions suggests it is difficult to maintain involvement in the longer term. Additional study incorporating Web-based and telephonic follow-up boosters might be more practical for patients to attend. Although there were some immediate effects for depressive symptoms, these were not long lasting. Additional research is needed to explore long-term benefits and most effective methods for delivery of this type of intervention.

To compare the efficacy of oral extended-release hydromorphone (HHER) administered every 24 hours with that of immediate-release hydromorphone (HHIR) administered four times daily

Patients were titrated to a stable HHER dose and randomized to individualized doses of HHER or HHIR for three to seven days before crossover to the second treatment. Nonrandomized, open-label titration phase for HHER occurred before double-blind phase.

• The sample was composed of 344 enrolled patients. Investigators analyzed data relative to 217 patients.
• Mean patient age was 58.3 years. Seventy-six patients were age 65 or older; 21 patients were age 75 or older.
• All patients had persistent moderate to severe pain related or unrelated to cancer.

The study was conducted in 37 sites in the United States.

Multicenter, randomized double-blind, crossover study

Mean of average pain intensity (API) scores, rated on a 0–10 scale, for the last two days before the pharmacokinetics/pharmacodynamics day of each double-blind period

Difference in treatments (HHER versus HHIR) in study 1 was 0.17 with a 90% CI. The difference in study 2 was 0.07 with a 90% CI. Authors noted no significant treatment-related difference in API scores or the amount of breakthrough medication used. Adverse events were opioid-related.

• The study was designed without a washout period between the crossover phases.
• Extended-release hydromorphone is no longer available in the United States.

Guidelines divided into four categories: Recommendations for diagnosis of IFDs, prophylaxis of IFDs (primary and secondary), empirical and pre-emptive antifungal therapy, and targeted treatments of IFDs, with the exception of rare yeasts and cryptococcosis, which were not addressed. A grading system similar to the one developed by IDSA for adults but specific to address pediatric concerns was used. Four components for grading of recommendation: evidence for efficacy from adult phase 2 and 3 trials, existence and quality of pediatric pharmacokinetic data and dosing recommendations, specific pediatric safety data and supportive efficacy data, and regulatory approval for use in pediatric age groups.

Diagnosis: Cultures, imaging studies; for aspergillus spp, galactomannan monitoring and serial screening two times weekly in pediatrics at a high risk for IFD (index of 0.5 or higher as +); data were too scarce in pediatrics to recommend β-D-Glucan testing; no general recommendation exists for the use of PCR because of the absence of standardization and validation. CT imaging recommended for high-risk pediatrics with febrile granulocytopenia persistenting beyond 96 hours or focal clinical findings.

Primary prophylaxis: In patients undergoing HSCT, prophylaxis is recommended during granulocytopenic phase until engraftment. Options include fluconazole (A-I), itraconazole or voriconazole (B-I), micafungin (C-I), and liposomal amphotericin B (C-III). Considerations for liposomal amphotericin B and posaconazole in children older than age 13 years. In the presence of graft-versus-host disease (GVHD), treatment with immunosuppression prophylaxis is recommended. Options include posaconazole for children aged 13 years or older (B-I), voriconazole for children aged 2 years or older (B-I), and itraconazole (C-III). In high-risk patients with de-novo or recurrent acute leukemia primary, itraconazole plus TDM (B-I), posaconazole  plus TDM 13 years or older, or liposomal amphotericin B (B-II) and fluconazole (C-I) is recommeded.

Secondary Prophylaxis: Bo data available for patients receiving mold-active antifungal prophylaxis, switching to a different class of mold-active antifungal agents seems reasonable. Patients receiving antifungal prophylaxis without mold activity should be given either caspofungin or liposomal amphotericin B for empirical therapy (no grading).

Targeted treatment: Candidemia treatments are caspofungin (B-II), fluconazole (B0IIU), liposomal amphotericin B (B-II), micafungin (B-11), voriconazole (B-II; restricted to children older than age 2 years and amphotericin B lipid complex [C-II]). A switch in class should be considered in patients with breakthrough infections. Aspergillus treatments are IV voriconazole coupled with TDM (A-I; restricted to patients older than age 2 years), liposomal amphotericin B (B-I), and amphotericin B lipid complex (B-II). Second-line treatment liposomal amphotericin B in amphotericin B naïve patients (B-I) and voriconazole plus TDM in voriconazole naïve patients (A-1: children older than age 2 years). No recommendation for or against hyperbaric oxygen to treat mucorales can be made; adjunctive use of deferasirox is not recommended; recommend initiation of amphotericin B and surgery.

Some recommendations were not graded because of lack of evidence in pediatrics, and some recommendations were based upon adult trials. In addition, there was an assumption that the same principals for pre-emptive therapy in adults could be applied in children.

Additional research is needed in epidemiology and surveillance of resistance, imaging and molecular diagnostics, exposure of antifungal agents in prophylaxis and treatment, and safety of antifungal drugs in the pediatric population.

To evaluate the effectiveness of an outpatient palliative care service

The specialized palliative care service included two physicians, two nurses, and a social worker specialized in palliative care providing home-based symptom management, 24-hour on-call services, psychological support, and coordination of care with local healthcare providers. Patients and caregivers completed study questionnaires at baseline and follow-up. Follow-up time frames ranged from a few days to seven weeks, with an average of 2.5 weeks. Questionnaires were completed in dialog with a trained psychologist

• N = 60 patients, 52 caregivers
• MEDIAN AGE = Patients: 67.5 years (range 32–97 years); caregivers: 41 years (range 29–91 years)
• FEMALES: 77% of caregivers
• KEY DISEASE CHARACTERISTICS: Not stated; all were in the end-of-life phase of care
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of caregivers were women and spouses.

• SITE: Single site  
• SETTING TYPE: Home  
• LOCATION: Germany

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

• Quasi-experimental

• Caregiver and patient questionnaires developed by researchers for this study
• Hospital Anxiety and Depression Scale

Patient and caregiver burden was significantly improved over the course of follow-up (p < .001). Caregivers and patients reported significant improvement in psychological support, support for activities of daily living, and communication between the patient and caregiver (p < .001). At baseline, 57% of caregivers showed clinically relevant anxiety scores (greater than 11), which decreased to 28% at follow-up (p < .001).

Palliative care services were associated with reduced caregiver perception of burden and reduced prevalence of clinically relevant anxiety among caregivers.

• Small sample (less than 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Other limitations/explanation: Questionnaires used to measure burden were not known and validated measures.

Findings suggest that palliative care services significantly can reduce caregiver sense of burden. This is in concert with previous findings that multicomponent interventions are effective in reducing caregiver strain and burden.

To explore the safety and efficacy of psilocybin in patients with advanced cancer and anxiety

Each participant received two treatment sessions, one with placebo and one with psilocybin, provided in random order. A niacin placebo was used, and psilocybin was given orally at a 0.2 mg/kg dosage. Sessions took six hours, provided in a clinical research unit with direct constant staff observation. Vital signs were measured 30 minutes before drug ingestion and at hourly intervals. All had continuous Holter monitoring. Study instruments were administered the day before each session, the day after the session, two weeks after sessions, and at monthly intervals for the next six months. At the end of each session, participants discussed their experiences. Participants were followed via monthly phone calls.

• The study reported on a sample of 12 patients.
• Patient age range was 36–58 years (average not reported).
• The sample was 92% female and 8% male.
• All patients had advanced stage cancer, including breast, colon, ovarian, peritoneal, salivary gland, and multiple myeloma. Duration of diagnosis ranged from 2 months to 18 years. All patients had a DSM-IV diagnosis of acute stress disorder, generalized anxiety disorder, or adjustment disorder with anxiety.
• Patients were excluded if they had central nervous system disease, cardiovascular illness, other severe comorbid uncontrolled conditions, or lifetime history of psychiatric disorders.
• Of the sample, 75% had prior experience using hallucinogenic agents, including LSD, mushrooms, peyote, and ayahuasca.

• Single site
• Outpatient setting
• California

• Patients were undergoing end-of-life care.
• The study has clinical applicability for end-of-life and palliative care.

A within-subjects, double-blind, placebo-controlled study design was used.

• Beck Depression Inventory (BDI)
• Profile of Mood States (POMS)
• State-Trait Anxiety Inventory (STAI)
• Brief Psychiatric Rating Scale
• Five Dimension Altered States of Consciousness Profile

All patients completed three months of follow-up, and eight patients completed six months of follow-up. Psilocybin induced a mild but statistically significant elevation of heart rate and diastolic blood pressure compared to the placebo. Heart rate peaked at two hours, with a peak rate of 81.5 on average. Blood pressure also peaked at two hours at a mean of 138.9 systolic, compared to a baseline average of 117. Holter monitor recording showed no significant differences from placebo session results. BDI scores dropped by almost 30% from the first session to one month after the second session (p = 0.05). This difference was sustained for six months (p = 0.03). Improvement in POMs were observed in 11 patients after psilocybin administration. STAI results showed improvement in state anxiety at one month (p = 0.001) and three months (p = 0.03).

As administered here, psilocybin administration was associated with sustained improvement in depression and anxiety, with no serious cardiovascular adverse effects.

• The study sample was small, with less than 30 patients.
• Patients did know the difference in experience between psilocybin and placebo, so patient blinding was not realistically accomplished.
• Given the results with potential of long-term effect, the control condition was not really valid, except for immediate vital signs responses.

Studies done in the 1960s and 1970s showed that hallucinogens had therapeutic benefits for patients with terminal cancer, and this pilot feasibility study shows similar results. As provided here, administration of psilocybin was accomplished in a clinical research unit with constant staff monitoring, which may not be widely practical in terms of cost and manpower. Further research in the use of hallucinogens in patients with anxiety and depression are needed to determine the most appropriate dosages, and whether they can be used in a less controlled setting for therapeutic benefit. The majority of patients had prior experience with hallucinogens; it is not clear if similar results would be seen if patients had no such prior experience.

Evaluate whether a brief cognitive behavioral (CBT) intervention can reduce stress and distress in women with breast cancer and identify characteristics of those most likely to benefit

After pre-surgery assessment, women were randomized to the intervention or control conditions. Assessments were conducted post-intervention and 12 months later in both groups. Participants were accrued over a five-year period. The intervention focused on provision of relaxation training at every session with daily home practice to address phsyiologic, cognitive, and emotional aspects of stress. Sessions were provided in a group setting for three hours per week for five weeks. Women who lived a great distance from the center where sessions were held were offered transport and/or overnight accommodations. Data also were obtained at 12 months post-intervention.

• N = 179    
• MEAN AGE = 53.7 years (SD = 10.2 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS All had breast cancer; the majority were stage II or lower. Sixty-two percent had excision, and the rest had mastectomy.

• SITE:  Single site  
• SETTING TYPE:  Outpatient

PHASE OF CARE: Transition phase after active treatment

Randomized controlled trial

• Hospital Anxiety and Depression Scale (HADS)
• Impact of Event Scale (IES)
• Perceived Stress Scale
• Silver Lining Questionnaire

Reports of global stress were lower in the intervention group at the end of the study (p = .003), but no difference was observed between groups at 12 months. Analysis of covariance showed a significant group-by-time effect on anxiety scores, with the intervention group reporting greater decreases in anxiety immediately after the intervention (p = .03). However, no difference was observed between groups at 12 months. Depression scores did not differ between groups. Global stress and anxiety decreased more among participants with higher global stress at baseline.

A brief CBT approach intervention may be beneficial in reducing short-term stress and anxiety among women with breast cancer. However, individuals in this study had anxiety and depression levels on the HADS that are not generally deemed to be clinically relevant. No long-term benefits were observed.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%
• Almost 50% loss to follow-up. Baseline anxiety and depression levels were not clinically significant, so measurement may have been subject to floor effects. Whether patients were in current treatment was unclear. The cost of transportation and accommodations may be prohibitive for this type of program for providers with a large catchment area. The control condition was not clearly described.

Findings suggest that CBT approach interventions in patient group settings might have a beneficial effect on stress and anxiety, but the study has several limitations. Effects seen were short-term, showing benefit immediately after the intervention, but were not maintained over the longer term. These results suggest that ongoing interaction probably is needed for patients to continue to practice relaxation and other behaviors.

To evaluate the evidence concerning the efficacy of Internet support groups (ISGs) in reducing symptoms of depression

• Databases searched were PubMed, PsycINFO, and Cochrane Database.
• Searched keywords were computer, Internet communication, and support.
• Studies were included if they employed an online peer-to-peer support group, incorporated either a depression outcome or involved an Internet support group relating to unipolar depression, or reported either quantitative or qualitative data.
• Authors did not specify exclusion criteria.
   

• Investigators retrieved a total of 158 studies.
• Investigators recorded study characteristics regarding design and other aspects of study quality. Investigators used no other method of quality evaluation.
• Of the studies retrieved, 16 involved a single component of peer-to-peer support. Of these 16, 4 reported that ISG had had a positive effect on symptoms of depression. Five of the 16 studies involved women with breast cancer.
• Twelve studies involved intervention components in addition to ISG. Only two of these reported positive results.
• Studies employed a bulletin board, chat room, or mailing list—alone or in combination. The duration of ISG intervention was 12 minutes to 12 months. Approximately 50% of interventions were moderated interventions, and the moderator was a healthcare professional.
• Only one study focused on rural participants.
• Of the final set of 28 studies, 9 involved patients with cancer. Most of these patients were women with breast cancer.
   

• The final number of studies included in the sample was 28.
• The mean range of participants was 10–2,373.
• Across studies, the median age range of patients was 26–65 years. Few samples focused on men, and most studies had a preponderance of women. 

• Multicomponent studies were less likely to yield significant positive outcomes than were stand-alone interventions (p = 0.01).
• Breast cancer ISGs were more successful than others (p = 0.02); however, all the studies involving ISGs originated from a single research group
• Authors noted no differences in outcomes between interventions involving chat rooms versus interventions involving static content.
• Authors noted no relationship between ISG participation and duration of intervention or ISG participation and outcomes or length of follow-up.
• Most studies were of low quality. Authors noted a correlation between low study quality and highly positive findings.
   

There is a need for high-quality research regarding the effect of ISGs on symptoms of depression.

This systematic review included data from studies available as of July 2007. Internet use and and social networking have increased since 2007—a fact that could alter the findings about the use and effect of ISGs. More research in this area is needed.

This review points to the need for high-quality research in this area. Theoretically, ISGs could be important for users who are isolated or unable to access face-to-face services readily; therefore, further research should be done.