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.
Griffiths, K.M., Calear, A.L., & Banfield, M. (2009). Systematic review on Internet Support Groups (ISGs) and depression (1): Do ISGs reduce depressive symptoms? Journal of Medical Internet Research, 11(3), e40-e40.
To evaluate the evidence concerning the efficacy of Internet support groups (ISGs) in reducing symptoms of depression
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.
Griffin, J.M., Meis, L., Carlyle, M., Greer, N., Jensen, A., MacDonald, R., & Rutks, I. (2013). Effectiveness of family and caregiver interventions on patient outcomes among adults with cancer or memory-related disorders: A systematic review. Retrieved from http://www.hsrd.research.va.gov/publications/esp/caregiver-intervention…
STUDY PURPOSE: To explore whether family-involved interventions for reducing burden and improving caregiver skills improve five outcomes for adult patients diagnosed with cancer or memory-related disorders (more specifically, to explore the benefits of psychosocial interventions delivered by family or a caregiver as compared to usual care or wait-listed care for those patients), and to identify the benefits of a caregiver or family psychosocial intervention as compared to a different family-related intervention or patient-directed intervention for those patients
PHASE OF CARE: Multiple phases of care
APPLICATIONS: Palliative care
The systematic review, focused on five interventions for cancer, indicated some support for family-involved interventions over usual care for decreasing patient anxiety and depression. Weak evidence was found for better patient outcomes with family-involved interventions as compared to patient-focused or health education/psychoeducational interventions. Family-involved interventions, directed toward specific subgroups of patients and those involving teaching of skills to meet patient needs, may be more effective for alleviating cancer symptoms and depression and anxiety than usual care. Little evidence was found that symptom management (e.g., pain, fatigue, nausea), quality of life, or relationships adjustment between the patient and family caregiver improved following interventions examined for the systematic review. Only 2 of the 27 trials received a “good” quality evaluation, mandating caution in applying findings to practice.
The systematic review found heterogeneous studies and evidence that family-involved interventions improved patient depression but had little effect on their anxiety and physical health.
Current evidence indicates that targeted interventions for specific conditions, behaviors, and symptoms of the cancer experience may improve patient outcomes and minimize caregiver burden. Previous evidence has shown that psychosocial/psychoeducational interventions with caregivers reduce caregiver strain and burden. Findings from this systematic review provide some evidence that such interventions aimed at the family, rather than the individual caregiver or caregiver/patient dyad, may not substantially improve caregiver outcomes, while skill training for family members may be helpful. Additional work in this area is needed to determine the best foci and method of delivery of these types of interventions.
Griffenberg, L., Morris, M., Atkinson, N., & Levenback, C. (1997). The effect of dietary fiber on bowel function following radical hysterectomy: A randomized trial. Gynecologic Oncology, 66, 417–424.
To evaluate the effect of fiber on bowel function by comparing increased fiber intake with instructions versus regular diet.
Women were randomized into two groups: high fiber (treatment) or regular diet (control). Both groups were evaluated at one, four, and seven months after surgery.
The treatment group received dietary counseling with instructions to increase their dietary intake to 30 to 40 g per day. Patients received all-bran cereal (unmarked) containing 15 g of fiber per bowl. Patients also were encouraged to increase their intake of insoluble fibers (eg, whole-grain, whole-wheat, and pumpernickel breads; all-bran cereal; butter; lima, pinto, and white beans; split and black-eyed peas; blackberries; boysenberries; raspberries; dried figs and prunes; artichokes; asparagus; Brussels sprouts; corn; parsnips; spinach; winter squash; turnip greens).
The study reported on a sample of 35 women with cervical cancer who had a type II or III radical hysterectomy.
University of Texas MD Anderson Cencer Center
This was a randomized controlled trial (RCT).
Patients with higher fiber intake had significantly less cramping abdominal pain and reports of straining, bowel-movement retention, more bowel movements with gas, and made in less than three minutes.