Grunberg, S., Chua, D., Maru, A., Dinis, J., DeVandry, S., Boice, J.A., … Herrstedt, J. (2011). Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: Randomized, double-blind study protocol—EASE. Journal of Clinical Oncology, 29, 1495–1501.
To evaluate the effectiveness of a single dose of fosaprepitant in combination with dexamethasone and 5-HT3 for chemotherapy-induced nausea and vomiting (CINV)
The study was conducted at multiple outpatient settings in 27 different countries.
All patients were in active treatment.
The study was a double-blind, randomized-controlled, parallel group.
The following measurement tools were used.
Grunberg, S.M., Dugan, M., Muss, H., Wood, M., Burdette-Radoux, S., Weisberg, T., & Siebel, M. (2009). Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy. Supportive Care in Cancer, 17, 589–594.
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 study was conducted at multiple outpatient settings in Vermont and Maine.
All patients were in active treatment.
The study was a prospective trial.
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.
Identifying effective single-day antiemetic regimens may improve adherence to supportive care guidelines and reduce nausea and vomiting symptoms in patients receiving chemotherapy.
Grover, V.K., Mathew, P.J., Yaddanapudi, S., & Sehgal, S. (2009). A single dose of preoperative gabapentin for pain reduction and requirement of morphine after total mastectomy and axillary dissection: Randomized placebo-controlled double-blind trial. Journal of Postgraduate Medicine, 55(4), 257–260.
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.
Randomized double-blind placebo-controlled trial
Pre-emptive administration of a single oral dose of gabapentin, 600 mg, led to a decrease in the use of postoperative analgesic.
The use of preoperative gabapentin was associated with improved pain control and quality of life, without excessive side effects.
Grothey, A., Nikcevich, D.A., Sloan, J.A., Kugler, J.W., Silberstein, P.T., Dentchev, T., . . . Loprinzi, C.L. (2011). Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. Journal of Clinical Oncology, 29, 412–427.
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 study was conducted in multiple outpatient settings throughout the United States.
The study was a double-blind, placebo-controlled randomized clinical trial.
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.
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.
Grossman, P., Zwahlen, D., Halter, J.P., Passweg, J.R., Steiner, C., & Kiss, A. (2015). A mindfulness-based program for improving quality of life among hematopoietic stem cell transplantation survivors: Feasibility and preliminary findings. Supportive Care in Cancer, 23, 1105–1112.
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.
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.
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.
Grosset, A.B., Roberts, M.S., Woodson, M.E., Shi, M., Swanton, R.E., Reder, R.F., & Buckley, B.J. (2005). Comparative efficacy of oral extended-release hydromorphone and immediate-release hydromorphone in patients with persistent moderate to severe pain: Two randomized controlled trials. Journal of Pain and Symptom Management, 29, 584–594.
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 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.
Groll, A.H., Castagnola, E., Cesaro, S., Dalle, J.H., Engelhard, D., Hope, W., ... & Lehrnbecher, T. (2014). Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic hematopoietic stem-cell transplantation. Lancet Oncology, 15, e327–e340.
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.
Groh, G., Vyhnalek, B., Feddersen, B., Führer, M., & Borasio, G.D. (2013). Effectiveness of a specialized outpatient palliative care service as experienced by patients and caregivers. Journal of Palliative Medicine, 16(8), 848–856.
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
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.
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.
Grob, C.S., Danforth, A.L., Chopra, G.S., Hagerty, M., McKay, C.R., Halberstadt, A.L., & Greer, G.R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68, 71–78.
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.
A within-subjects, double-blind, placebo-controlled study design was used.
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.
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.
Groarke, A., Curtis, R., & Kerin, M. (2013). Cognitive-behavioural stress management enhances adjustment in women with breast cancer. British Journal of Health Psychology, 18, 623-641.
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.
PHASE OF CARE: Transition phase after active treatment
Randomized controlled trial
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.
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.