Blagden, M., Hafer, J., Duerr, H., Hopp, M., & Bosse, B. (2014). Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: Pooled analysis of extension phases of two phase III trials. Neurogastroenterology and Motility, 26, 1792–1801.
To evaluate the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain.
474 patients received open-labeled OXN PR during 52 weeks of extension phases of two studies, having completed 12 weeks of double-blinded, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) (n = 160) or OXN PR (n = 162). The starting dose was the effective analgesic dose of OXY or OXN that the patient received at the end of the double-blind phase. Dose titration was to a maximum of 80 mg per day (OXN3001S) or 120 mg per day (OXN3006S) at the discretion of the investigator. Use of laxatives and analgesic rescue therapy was recorded in patient diaries. Oxycodone immediate-release (IR) and bisacodyl were provided for the first seven days of the extension phase. Protocols for rescue medicines and laxatives were prescribed according to standard protocols of the investigational sites. There were seven mandated office visits.
Improvement in bowel function was seen when patients switched from Oxy PR in the double-blinded phase to OXN PR in the extension phase, resulting in a clinical reduction (greater points) in BFI score: At the start of the extension phases, mean BFI score was 44.3 (SD = 28.13) and was 29.8 (SD = 2.36) for patients who had received OXN PR in the double-blinded phase. One week later, BFI scores were similar for the two groups (26.5 [SD = 24.4] and 27.5 [SD = 25.6], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-hour pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed.
Pooled data demonstrated OXN PR in patients with moderate-to-severe chronic pain is an effective long-term therapy for patient opioid-induced pain. Improvement in bowel function was seen during the double-blinded studies and was continued throughout the 52 weeks of OXN PR versus Oxy PR in this pooled analysis. No new or unexpected safety issues were observed, and patient satisfaction was high and maintained throughout the 52 weeks.
Prolonged-release oxycodone/naloxone (OXN PR) is a good option for patients with opioid-induced constipation.
Blackwell, K., Semiglazov, V., Krasnozhon, D., Davidenko, I., Nelyubina, L., Nakov, R., . . . Harbeck, N. (2015). Comparison of EP2006, a filgrastim biosimilar, to the reference: A phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Annals of Oncology, 26, 1948–1953.
To compare the biosimilar to reference filgrastim
Patients were randomized to receive the biosimilar or filgrastim for the duration of treatment or to alternate at each chemotherapy cycle. Chemotherapy was given every three weeks for six cycles. Patient assessments were done at baseline, on day 1 of each cycle. For cycles 2–6, complete blood counts were assessed on day 7 and daily thereafter.
The number of consecutive days of neutropenia was 1.17 in the biosimilar group and 1.2 in the filgrastim group. No significant differences existed in the time to ANC recovery or adverse events. In those receiving the biosimilar, fever episodes were reported in 15% compared to 4.3% of those receiving filgrastim.
This study showed no clinically meaningful differences in neutropenia-related outcomes between patients receiving figrastim and a colony-stimulating factor (CSF) biosimilar.
The findings showed similar clinical results with filgrastim and this CSF biosimilar.
Blackwell, L., Petroni, G., Shu, J., Baum, L., & Farace, E. (2009). A pilot study evaluating the safety and efficacy of modafinil for cancer-related fatigue. Journal of Palliative Medicine, 12, 433–439.
The study's primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue. Its secondary aim was to determine the effect of modafinil on depression, quality of life, functional status, and cognitive function.
Participants were given 100 mg of modafinil daily for weeks 1 and 2, and then 200 mg daily for weeks 3 and 4. Participants older than 80 were dose-reduced and received 50 mg of modafinil daily for weeks 1 and 2, then 100 mg daily for weeks 3 and 4. There was no control group.
Testing was completed at baseline, week 2, and at the completion of the trial.
This was a prospective, open-label pilot study.
Fatigue (as measured by the BFI) was improved at week 2 for 46% of participants; at week 4, 75% had a significantly improved score (p = 0.025). Functioning (as measured by the FACT-BR) showed an improvement in all subsets of well-being at weeks 2 and 4 (p < 0.05) except social/family. Depression (as measured by the HADS) declined significantly at weeks 2 and 4 (p < 0.001).
Functional status (as measured by the Barthel Index) did not change, but overall ECOG performance status improved, with 40% of patients improving at least one level. Cognitive function was not significantly changed, although the TMT-B did show a trend of overall improvement.
Modafinil did not significantly improve learning and memory, fine motor ability, verbal fluency, or executive function, but results are limited due to the small sample size.
Blackwell, K., Donskih, R., Jones, C.M., Nixon, A., Vidal, M.J., Nakov, R., . . . Harbeck, N. (2016). A comparison of proposed biosimilar LA-EP2006 and reference pegfilgrastim for the prevention of neutropenia in patients with early-stage breast cancer receiving myelosuppressive adjuvant or neoadjuvant chemotherapy: Pegfilgrastim randomized oncology (supportive care) trial to evaluate comparative treatment (PROTECT-2), a phase III, randomized, double-blind trial. Oncologist, 21, 789–794.
To compare the efficacy and safety of a pegfilgrastim biosimilar to reference pegfilgrastim
Patients were randomized to receive 6 mg of either reference pegfilgrastim or a biosimilar. The colony-stimulating factor (CSF) was given on day 2 of each cycle. ANC was measured on day 1 of cycle 1, then daily until recovery after nadir or until day 15. A margin of one day of neutropenia was established as the margin for noninferiority analysis.
All study outcomes were similar in both groups. Over 95% of both groups had musculoskeletal adverse events, including bone pain, myalgia, arthralgia, and back pain (13.7%–16.1% of patients).
The CSF biosimilar evaluated here demonstrated similar efficacy and safety to that of the reference pegfilgrastim.
Pegfilgrastim and the CSF biosimilar evaluated were shown to be therapeutically equivalent.
Blacklock, R., Rhodes, R., Blanchard, C., & Gaul, C. (2010). Effects of exercise intensity and self-efficacy on state anxiety with breast cancer survivors. Oncology Nursing Forum, 37, 206–212.
To determine if acute exercise reduces state anxiety in breast cancer survivors
Participants recruited were randomly assigned to a light or moderate intensity group and were asked to complete both moderate and light intensity exercise on two different days. Exercise sessions were done by cycling. Prior to exercise, questionnaires for anxiety and self-efficacy were completed. Participants cycled for 20 minutes, staying with standardized heart rate ranges as defined for light and moderate intensity. Questionnaires were repeated after each exercise session following an eight-minute rest.
The study has clinical applicability for late effects and survivorship.
A randomized, experimental, repeated-measures design was used.
There were no differences between day 1 and 2 for anxiety and self-efficacy. Repeated measures ANOVA on anxiety showed a main effect for time (p < 0.01), with anxiety decreasing across the time of exercise. The intensity of the exercise was not significant. There were no differences between breast cancer survivors and others. Self-efficacy measures showed a main effect for time (p < 0.01), but no differences between breast cancer survivors and others or between exercise intensities. Breast cancer survivors and others reported similar pre-exercise state anxiety levels. There was a significant reciprocal relationship between self-efficacy and state anxiety both pre- and post-exercise (p < 0.05).
Exercise appears to have a short-term effect in reducing anxiety and increasing perception of self-efficacy.
Studies with longer-term exercise interventions and in participants with higher levels of anxiety may be helpful in exploring these issues. Long-term findings suggest that the specific approach to management of anxiety during the cancer diagnostic phase does not appear to significantly impact anxiety and depression in women with low-risk abnormal findings. The timing of depression might suggest that extended follow-up after diagnostic testing and treatment may be associated with depression for some women. Which of the strategies examined here offer the best balance between benefits and harms is a matter of continuing debate.
Blackhall, L., Petroni, G., Shu, J., Baum, L., & Farace, E. (2009). A pilot study evaluating the safety and efficacy of modafinal for cancer-related fatigue. Journal of Palliative Medicine, 12, 433–439.
The primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue (CRF) in patients with cancer.
The secondary aim was to assess the effect of modafinil on depression, quality of life (QOL), functional status, and cognitive function.
After initial assessment for all outcome measures, patients were treated with self-administered modafinil at an initial dose of 100 mg per day during weeks one to two. During weeks three to four, the dose was increased to 200 mg per day. All study parameters were reassessed at week two and at week four (completion of the trial).
This was an open-label pilot study.
BFI was improved at two weeks for 46% of participants, and at four weeks, 75% had a significantly improved score (p = 0.025). FACT-BR showed an improvement in all subsets of well-being except social/family at two and four weeks (p < 0.05). HADS score declined significantly at two and four weeks (p < 0.001). Cognitive function was not significantly changed, except TMT-B showed a trend for an overall improvement. Functional status (Barthel Index) did not change, but overall performance status (ECOG) improved, with 40% of patients improving at least one level. Most side effects were mild. Side effects seen were dizziness, nausea, diarrhea, and heartburn.
Modafinil use was associated with improvement in fatigue, depression, and QOL measures and was well tolerated.
Björneklett, H. G., Lindemalm, C., Ojutkangas, M. L., Berglund, A., Letocha, H., Strang, P., & Bergkvist, L. (2012). A randomized controlled trial of a support group intervention on the quality of life and fatigue in women after primary treatment for early breast cancer. Supportive Care in Cancer, 20, 3325–3334.
To evaluate the effects of a psychosocial support intervention on health-related quality of life (QOL) and fatigue.
Participants were randomized to an intervention or usual care control group. The intervention consisted of education sessions mixed with exercise, relaxation training, massage, qigong, visualization, and social activities, such as concerts and museum and restaurant visits. As reported in a previous pilot study, participants were residents at a spa-type facility during the intervention. The intervention was provided by an interdisciplinary group comprising physicians, psychologists, an art therapist, a massage therapist, a dietician, social workers, and a trained qigong provider for seven days. Follow-up was performed at two, six, and 12 months. Participants in the usual care control were only provided follow-up data collection.
The study was a randomized, controlled trial.
Fatigue scores were similar in both groups and declined over time up to 12 months in both groups. There were no differences in fatigue levels over time between the groups. There were no significant effects of the intervention on QOL measures.
The multimodal intervention demonstrated no significant effect on QOL or fatigue.
The specific approach providing a multifaceted, psychoeducational type of intervention was not shown to affect fatigue or QOL in women with breast cancer. The most effective content, duration, and frequency of psychosocial and multimodal support interventions were not clear.
Björneklett, H.G., Rosenblad, A., Lindemalm, C., Ojutkangas, M.L., Letocha, H., Strang, P., & Bergkvist, L. (2013). Long-term follow-up of a randomized study of support group intervention in women with primary breast cancer. Journal of Psychosomatic Research, 74(4), 346–353.
Long-term follow-up to evaluate quality of life after support group intervention in a randomized group of women with primary breast cancer presenting for postoperative radiotherapy.
The current study is a long-term follow-up 5–9 years after randomization into groups. The intervention and control groups were stratified by chemotherapy or nonchemotherapy treatment. The intervention was a one-week support group with four days of follow-up two months postintervention during residential care at the Foundation of Lustgården Mälardalen. The intervention involved lectures and group discussions about the etiology of cancer, risk factors, treatment, physical and psychological effects, and coping strategies. Patients engaged in physical exercise, relaxation, Qigong, and nonverbal communication exercises, as well as art and dance therapy. All participants completed questionnaires at baseline and follow-up questionnaires at 2, 6, and 12 months postintervention. The control group participated only in routine follow-up at the Department of Oncology or the Department of Surgery.
Fatigue symptoms improved over time, which was a significant finding in the intervention and control groups. Being upset about hair loss improved over time in the intervention group. High anxiety scores improved over time and were not significantly different between the two groups in long-term follow-up. Depression scores were high at follow-up for seven women in each group, and no significant difference was found at baseline and postintervention, adjusting for covariates. Neither group showed improvement between the 12-month follow-up and long-term follow-up.
Effects of support group intervention may provide a sense of security that can fade over time, reversing improvements in anxiety and depression. Treatment-related fatigue may improve over time. Significant improvement was found in cognitive function, body image, and future perspective, but no significant effect was found on levels of anxiety and depression.
Women who have received chemotherapy have greater symptom severity and may benefit more on global health and cognitive function fatigue, when compared to women who have not received chemotherapy. Additional research is needed to evaluate the influence of exercise and psychosocial support interventions, according to patient needs for content, duration, and an assessment of spiritual well-being using the Functional Assessment of Chronic Illness Therapy (FACIT).
Björneklett, H.G., Lindemalm, C., Rosenblad, A., Ojutkangas, M.L., Letocha, H., Strang, P., & Bergkvist, L. (2012). A randomised controlled trial of support group intervention after breast cancer treatment: Results on anxiety and depression. Acta Oncologica, 51, 198–207.
To evaluate the effect of a support program on anxiety and depression in patients with breast cancer
The intervention was a weeklong multidisciplinary residential program. The intervention took place within four months after the end of tumor treatment and ran for seven days, followed by four days of follow-up two months after the initial visit. The team consisted of oncologists, social workers, art therapists, massage therapists, a dietitian, and a mindfulness practitioner.
A randomized controlled trial design was used.
Hospital Anxiety and Depression Scale (HADS)–Swedish version
After 12 months, 10% in the intervention group versus 19% in the control group had a high anxiety score (p = 0.055).
Support group intervention including education about the disease and psychological reactions, mixed with art and dance therapy, qigong, and relaxation, was shown to positively influence anxiety levels among patients with breast cancer over time, whereas depression levels were unaffected by the intervention.
Because of costs and time constraints, the ability of this program to be replicated is suspect. The particular components of the program that provided the most effectiveness were not analyzed and therefore cannot be reproduced or further studied.
Bjordal, J.M., Bensadoun, R.J., Tuner, J., Frigo, L., Gjerde, K., & Lopes-Martins, R.A. (2011). A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis. Supportive Care in Cancer, 19, 1069–1077.
Review the effects of low level laser therapy (LLLT) in prevention and treatment of oral mucositis induced by cancer therapy. Meta-analysis was done, and all results are provided.
Databases searched were Medline, EMBASE, CINAHL, PedRo, and Cochrane Controlled Trial Register. Hand searching in physiotherapy and medical journals from several countries also were used.
Search keywords were low level laser therapy, low intensity laser therapy, low energy laser therapy, phototherapy, oral mucositis, cancer, chemotherapy, radiation therapy, and specific laser types.
Studies were included if they
A total of 149 papers were initially retrieved. Literature was evaluated using the Jadad checklist and inclusion of study funding sources.
A final sample of 11 trials published from 1997–2009 included 415 patients. Samples ranged from 21–70 subjects and included those receiving chemotherapy, radiation therapy, combined therapy, and transplant cases. One study was done in children.
Moderate to strong evidence was found for effectiveness of LLLT in the prevention of OM, reduced duration and severity of OM, and reduced pain with doses of 1–6 joules per point. Trials aimed at prevention started LLLT seven days before cancer treatment regimens, and effective dosing seen ranged from 1–6 joules. This meta-analysis supported the effectiveness of LLLT in the dosage ranges reported here for the prevention and management of oral mucositis.
The quality of studies was determined to be high; however, substantial variation existed in the actual treatment procedures, number of treatments, timing of treatments, and heterogeneity in the overall findings.