Kissane, D.W., Bloch, S., Smith, G.C., Miach, P., Clarke, D.M., Ikin, J., . . . McKenzie, D. (2003). Cognitive-existential group psychotherapy for women with primary breast cancer: A randomized controlled trial. Psycho-Oncology, 12, 532–546.
The intervention was cognitive-existential therapy (CEGT) provided in nine Australian hospitals. Existential themes of anxiety about death and uncertainty were incorporated into six goals of therapy: promoting a supportive environment, facilitating grief work over multiple losses, altering maladaptive cognitive patterns, enhancing problem-solving and coping skills, fostering a sense of mastery, and sorting out priorities for the future. The CEGT group had 20 weekly sessions, 90 minutes each, over six months. The control group had three 50-minute relaxation classes using progressive muscle relaxation with guided imagery. Measurements were taken at baseline, 6 months, and 12 months after the intervention. The intervention was offered by 15 therapists recruited from psychiatry, psychology, social work, occupational therapy, and oncology nursing staff. All therapists received specialized training and supervision through a series of workshops using 68-page manual.
Nine Australian hospitals
A randomized controlled trial/longitudinal study design was used.
Kirshner, J.J., Heckler, C.E., Janelsins, M.C., Dakhil, S.R., Hopkins, J.O., Coles, C., & Morrow, G.R. (2012). Prevention of pegfilgrastim-induced bone pain: A phase III double-blind placebo-controlled randomized clinical trial of the University of Rochester Cancer Center Clinical Community Oncology Program Research Base. Journal of Clinical Oncology, 30, 1974–1979.
To determine whether naproxen could prevent or decrease the incidence and/or severity of pegfilgrastim-induced bone pain
A baseline assessment questionnaire was administered prior to treatment asking the presence, location, and duration of bone or joint pain, as well as how the pain was treated. A second set of questions asking whether there was development of new bone or joint pain, location, onset, duration, and severity of the effect of the assigned medication was given to patients at the time of pegfilgrastim administration. Any additional analgesia taken by the patient was also recorded. Questionnaires were completed at home and mailed. Patients were telephoned at home as a reminder to mail in their questionnaires. Enrolled patients received 500 mg of naproxen PO or placebo instructed to take prior to pegfilgrastim and continue BID. Patients were then asked to record pain severity on a 0–10 scale and duration in a daily diary. Serious adverse events (SAEs) were reported to local investigators at the University of Rochester Cancer Center Community Clinical Oncology Program research base. Other symptoms were recorded but not reportable (e.g., sleep disturbance, pain other than bone pain, fatigue).
The study was a phase III, double-blind, placebo-controlled, randomized trial.
African Americans experienced more bone pain than white patients. The naproxen group showed improvement in pain reduction versus placebo. Area under the curve for pain was 7.71 for the placebo group and 6.04 for the naproxen group (p = 0.037). Naproxen decreased maximum pain from 3.40 to 2.50 (p = 0.005), incidence from 71.3% to 61.1% (p = 0.020), duration from 2.40 to 1.92 (p = 0.009), and severe pain from 27% to 19.2% (p = 0.048). Bone pain reached maximum at day 3, where naproxen patients experienced the most benefit. Patients receiving naproxen took less prescription and nonprescription pain medication. Six SAEs occurred in the naproxen group, and six SEAs occurred in the placebo group, with all SAEs unlikely or determined to be unrelated to the intervention.
There is a high incidence of pain in patients receiving pegfilgrastim. Naproxen seems to decrease incidence, duration, and severity.
The pain questionnaire was not presented in the article, and further studies may not reproduce similar results. Patients were called at home to complete the survey; prescription and nonprescription medications that were taken in addition to the naproxen and timing of the survey may have impacted results. It is also possible that the individual responding to the call may not have been the study participant. The study does not address whether individuals with other existing pain conditions were in the study or excluded or whether there were other pain conditions present at the start of the study that may have impacted results.
This study indicates there a is a difference in pain experience with different races, which may impact practice in terms of treating pain and the patient population being treated. Additional research and education are needed to investigate this difference. These results may be helpful in treating some patients’ pain; however, more work is needed to find treatments for those who cannot seek this treatment or who derive limited or no benefit from it. More than 60% of patients in this study still experienced pain, with approximately 20% experiencing severe pain. It seems this study has a good start to recognizing the existence of pegfilgrastim-induced pain and has tested a somewhat helpful intervention. However, there is still a need for more studies with different approaches to pain control and factors to predict incidence, severity, and ability to prevent pegfilgrastim-induced bone pain. The benefit of using naproxen is that it is low cost and has very few SAEs, which will need to be considered in future studies.
Kirova, Y. M., Fromantin, I., De Rycke, Y., Fourquet, A., Morvan, E., Padiglione, S., . . . Bollet, M. A. (2011). Can we decrease the skin reaction in breast cancer patients using hyaluronic acid during radiation therapy? Results of phase III randomised trial. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology, 100(2), 205–209.
To evaluate the benefit of hyaluronic acid in management of radiodermatitis
Women who developed a grade 1 dermatitis with radiotherapy were randomized to use either hyaluronic acid cream or a simple urea-based emollient once daily. Patients were advised to shower one-to-two times daily. Clinical evaluation of the skin was done weekly by the radiation oncologist. Pain and quality of life were assessed at the end of treatment on day 30. The study endpoint was a success as defined by disappearance of erythema 30 days after its occurrence.
The study used a randomised open-label phase III design.
Overall, 36.5% of participants withdrew prematurely because of worsening of eipthelitis, patient refusal, change in treatment, or use of another product. In the intent to treat population (all registered), there was a 27.3% treatment failure with hyaluronate and a 38.8% treatment failure with emollient. Power analysis showed that 100 per study group were needed. With drop outs, this study was underpowered.
The study did not demonstrate any significant differences in epithelitis between those using hyaluronic acid or emollient topically. The study was insufficiently powered to provide any firm conclusions.
Study findings are inconclusive because of the study limitations. Findings suggest that hyaluronic acid and urea-based emollients topically may provide similar results for prevention of low-grade radiodermatitis. These findings should be viewed with caution because of the study design limitations and lack of sufficient sample size to meet power requirements.
King, K. (2010). A review of the effects of guided imagery on cancer patients with pain. Complementary Health Practice Review, 15, 98–107.
To review the effects of guided imagery on patients with cancer experiencing pain
The type of report was systematic review.
Databases searched were PubMed, CINAHL, PsycINFO, and Cochrane Library.
Search keywords were guided imagery, cancer pain, and systematic review.
Studies were included if they were review articles published in English since 1985; the search was not limited to randomized controlled trials (RCTs).
Studies were excluded if they were clinical trials or systematic reviews that did not utilize guided imagery as an intervention, did not specifically investigate cancer pain, were not a clinical study but rather a summary of guided imagery, had a qualitative design, and were not conducted within the study time frame.
In order to focus on the most current research, this review targeted articles published during 2001–2008.
Five studies included pain as either a primary or secondary outcome measure. In three of those, pain intensity and pain-related distress decreased in the guided imagery intervention versus control for pain intensity and pain-related distress, average pain score decreased, and there was a decrease in body discomfort.
It is difficult to give concrete recommendations that guided imagery will work for all patients who suffer from cancer pain. However, based on the information from these reviews, guided imagery can be recommended as a potential aid in the relief of pain associated with cancer.
Inconsistencies and limitations included the small sample size, different patient populations, different scripts, and frequency of medication administration.
There is inconsistency in the methodological qualities of these trials. Further research is necessary to provide better evidence for the use of guided imagery in cancer pain.
King, M., Deveaux, A., White, H., & Rayson, D. (2012). Compression garments versus compression bandaging in decongestive lymphatic therapy for breast cancer-related lymphedema: A randomized controlled trial. Supportive Care in Cancer, 20, 1031–1036.
To compare effects of compression garment versus compression bandaging in women receiving complete decongestive therapy for arm lymphedema
Therapy for all patients included manual lymphatic drainage five days per week over a two-week period. During initial treatment, patients were randomly assigned to wear a compression glove and sleeve or compression bandages day and night as tolerated. At the end of two weeks, all were provided with a new sleeve and glove, which was worn only during the day. They were instructed in skin care. Participants completed study measurement of lymphedema at baseline and on days 5 and 10 and then at 3 months.
There were no difference between groups in arm volume or DASH scores at 10 week or 3 months. There were no differences between groups in VAS symptom scores. There was a trend toward lower arm volumes but higher DASH scores with compression bandaging.
Findings showed no significant differences in effect of compression bandaging versus use of compression garments during the first two weeks of therapy for arm lymphedema.
Findings suggest that compression garment and compression bandaging use during initial phase of CDT for arm lymphedema yielded similar results. There was a trend suggesting lower arm volume, but higher disability scores with bandaging; however, no firm conclusions can be drawn due to lack of statistical significance and the small sample size. Ongoing work is important to determine which treatment approaches are better tolerated by patients and degree of comparative effectiveness combined with tolerance.
Kim, S.Y., Song, J.W., Park, B., Park, S., An, Y.J., & Shim, Y.H. (2011). Pregabalin reduces post-operative pain after mastectomy: A double-blind, randomized, placebo-controlled study. Acta Anaesthesiologica Scandinavica, 55(3), 290–296.
To investigate the safety and effectiveness of pregabalin for reducing postoperative pain in patients who have undergone mastectomy
Patients were randomly assigned to receive either pregabalin or placebo at 1 hour before surgery and at 12 hours after the initial dose. All patients received the same anesthesia and all received 100 mg aceclofenac twice a day the day after surgery. Assessment of pain and for adverse effects was done at 1, 6, 24, and 48 hours postoperatively. If a patient’s pain intensity was 5 or greater or if the patient requested analgesia, additional pain medication was provided. After discharge from the hospital, at one week and one month postoperatively, patients were contacted by phone for pain scoring.
Double-blind placebo-controlled randomized study
Perioperative pregabalin may improve postoperative pain control in patients who have undergone mastectomy.
Perioperative administration of pregabalin may be helpful in the management of postoperative pain. This study does not establish the most effective timing of administration. Nurses should be aware of the common side effects of pregabalin (dizziness and sedation), which other studies have established. These side effects may complicate postanesthesia assessment.
Kim, S. W., Shin, I. S., Kim, J. M., Kim, Y. C., Kim, K. S., Kim, K. M., . . . Yoon, J. S. (2008). Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depression. Psychiatry and Clinical Neurosciences, 62, 75–83.
To study the effectiveness of mirtazapine on various cancer-related symptoms, such as nausea, sleep disturbance, pain, and depression.
Patients were treated at a starting dosage of 15 mg of mirtazapine in orally disintegrating tablets a day. The dosage was titrated between 15 and 45 mg per day based on clinical judgment. Mean treatment dosage was 19.6 mg per day in the total population and 22.9 mg in those who completed the study. Patients were administered serial assessments at baseline and on days 1, 3, 5, 7, 14, and 28.
The study used a prospective, open-label, repeated measure design.
Nausea improved significantly from day 1 after administration of mirtazapine (p < 0.001). Improvement was sustained throughout the treatment and seemed to work best for patients actively receiving chemotherapy. In addition, anorexia improved. All sleep measures improved, many as early as day 1, but at least one measure (ease of wakening) did not improve until day 5 (p < 0.001). Mirtazapine increased sleepiness in one of three patients, but this resolved after several days on therapy. Reduction in pain scores (p < 0.5), improvement in depression score (p < 0.01), and overall quality of life (QOL) (p < 0.01) were noted as well.
Mirtazapine may be helpful in treating the cancer-related symptoms of nausea, sleep disturbance, anorexia, pain, and depression, as well as improving QOL.
Mirtazapine may be useful in treating chemotherapy-related symptoms, especially sleep disturbance and nausea, in patients with malignant cancers.
Kim, H.J., Shin, S.W., Song, E.K., Lee, N.R., Kim, J.S., Ahn, J.S., . . . Kang, J.H. (2015). Ramosetron versus ondansetron in combination with aprepitant and dexamethasone for the prevention of highly emetogenic chemotherapy-induced nausea and vomiting: A multicenter, randomized phase III trial, KCSG PC10-21. Oncologist, 20, 1440–1447.
To compare the efficacy and safety of the combination of ramosetron, aprepitant, and dexamethasone (RAD) with the efficacy and safety of the combination of ondansetron, aprepitant, and dexamethasone (OAD) in treating highly emetogenic chemotherapy (HEC)-induced nausea and vomiting
Patients were assigned to either the RAD or OAD groups (1:1 ratio) according to a stratified block randomization table. Aprepitant (125 mg one hour prior to chemotherapy on day 1 and 80 mg on days 2–3) and dexamethasone (12 mg 30 minutes prior to chemotherapy on day 1 and 8 mg on days 2–4) were administered orally. Ramosetron (0.3 mg on day 1) and ondansetron (16 mg on day 1) were administered IV to the RAD group and OAD group, respectively, 30 minutes before chemotherapy. Rescue antiemetics were used per the attending physician’s discretion. Patients were then asked to keep a record of vomiting or retching episodes in a diary and Rhodes Index of Nausea and Vomiting scores for five days.
Complete response (CR) rates for the acute, delayed, and overall phases were similar for both the ramosetron- and ondansetron-based regimens. No differences existed between groups in the use of rescue medication.
RAD was noninferior to OAD in the prevention of HEC-induced nausea and vomiting irrespective of patient age, type of cancer, or chemotherapeutic regimen. RAD demonstrated efficacy in the acute, delayed, and overall phases. RAD was more effective than OAD in men.
RAD can be considered a standard regimen for HEC-induced nausea and vomiting. The adverse event rate is similar to ondansetron.
Kimura, H., Yamamoto, N., Shirai, T., Nishida, H., Hayashi, K., Tanzawa, Y., . . . Tsuchiya, H. (2015). Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study. Cancer Medicine, 4, 333–341.
To evaluate the efficacy of combination antiemetic therapy including 5HT3 receptor antagonists, neurokinin-1 (NK1) receptor antagonists, and dexamethasone for multiple highly emetogenic anticancer agents in patients with bone and soft tissue sarcoma; to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron
A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen the second and fourth courses. Patients in the granisetron arm received granisetron during the first and third courses and palonosetron the second and fourth. All patients received an NK1 receptor antagonist and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg of palonosetron on day 1, and patients receiving the granisetron regimen received 3 mg of granisetron twice daily on days 1–4 and once on day 5. Patients were followed for 10 days during each course for efficacy and safety endpoints. On days 4 and 10, patients responded to a questionnaire about emetic experiences and rescue medication use. Nausea severity was rated from 0–10 according to subjective assessments during the acute and delayed phases.
Randomized, single-blinded crossover study
The overall complete response rate was 66 out of 96 courses (69%) for the acute phase, 38 out of 96 (40%) for the delayed phase, and 33 out of 96 (34%) overall. In the acute phase, complete responses were achieved in 34 out of 48 courses (71%) of the palonosetron regimen and 33 out of 48 courses (69%) of the granisetron regimen. In the delayed phase, complete responses were achieved in 18 courses (38%) of the palonosetron regimen and 20 courses (42%) of the granisetron regimen. There were no statistically significant differences in complete responses for either regimen. Patient preference was recorded for 15 patients. Two patients (13%) preferred palonosetron, three patients (20%) preferred granisetron, and 10 patients (67%) reported that both antiemetic regimens had similar efficacies. The amount of time till the first administration of rescue therapy tended to be longer in the granisetron regimen (5.65 days) compared to palonosetron (5.12 days), but this was not statistically significant (p = 0.115). For palonosetron, regimen rescue therapy was administered in 24 out of 48 courses compared to 17 out of 48 courses for the granisetron regimen. Nausea severity was slightly greater with granisetron (3.58 acute phase, 4.04 delayed) than palonosetron (3.40 acute phase, 3.92 delayed), but this was not statistically significant.
Antiemetic therapy with a three-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting during chemotherapy with multiple highly emetogenic chemotherapy agents for bone and soft tissue sarcoma. However, consecutive-day granisetron was not inferior to single-shot palonosetron for treating chemotherpy-induced nausea and vomiting.
This study demonstrated that granisetron given in consecutive-day dosing was not inferior to single-dose palonosetron in triplet therapy for highly emetogenic chemotherapy in patients with bone or soft tissue sarcoma. However, neither combination therapy was adequate to control chemotherapy-induced nausea and vomiting in this population. The development of novel antiemetic agents, or new combination therapies with existing agents such as olanzapine, was recommended. The appropriate dosing of all agents in combination therapy is an important consideration.