Cepeda, M.S., Chapman, C.R., Miranda, N., Sanchez, R., Rodriguez, C.H., Restrepo, A.E., . . . Carr, D.B. (2008). Emotional disclosure through patient narrative may improve pain and well-being: Results of a randomized controlled trial in patients with cancer pain. Journal of Pain and Symptom Management, 35, 623–631.
To determine if a structured approach using patient narrative in patients with advanced cancer decreases pain and improves sense of well-being
Patients were randomized into one of three groups: (1) narrative group, (2) questionnaire group, or (3) control group. Patients in the narrative group were asked to write about how cancer affected their lives, calling upon their deepest thoughts, feeling, and fears, and to write for at least 20 minutes once a week. Patients in the questionnaire group were asked to complete a pain questionnaire as an attentional control. Patients in the control group were asked to attend weekly medical follow-up visits and receive usual care. All patients were seen weekly in the clinic for eight weeks. Three weeks after randomization, research personnel called patients to remind them about completing narratives, filling out the questionnaire, and coming to the office for follow-up. Research personnel who collected data were blinded to group assignment. Patients rated their average pain intensity during the prior week in clinic visits. Investigators rated emotional content of the narratives.
The study was a randomized, single-blinded, controlled trial.
There were no differences between groups in outcomes measured. More than half (53%) of patients in the narrative group completed narratives as requested, 86% of patients in the questionnaire group completed the questionnaire, and 90% of patients in the control group kept all clinic appointments. Twenty patients did not demonstrate any emotional disclosure in narratives. Five patients had strong emotional content of narratives, and these patients had lower pain intensity scores.
Participation in writing narratives as structured in this study did not have any impact on pain or well-being. Only half of the patients fully participated in the narrative writing as designed.
Study findings suggest that having patients write narratives for emotional disclosure to reduce pain is not effective. The apparent lack of actual emotional content in the majority of narratives reviewed in this study suggests that patients need assistance to identify and disclose these aspects of their experience. It is not clear whether patients may have concerns about privacy in terms of what content they provided in this research.
Cepeda, M.S., Carr, D.B., Lau, J., & Alvarez, H. (2010). Music for pain relief. Cochrane Database of Systematic Reviews 2010(8).
To evaluate the effect of listening to music on acute or chronic cancer pain; to relate the effect of listening to music on analgesic requirements
Music has limited utility in clinical practice for pain reduction: A music intervention was associated with minimal reduction in pain intensity. A music intervention was associated with a small reduction in opioid use for the treatment of acute pain. The reduction was smaller than that associated with the use of an NSAID or paracetamol.
The analysis provided little support for the effectiveness of music in the reduction of pain: The size of effects is small, and their clinical relevance is unclear. On the other hand, the analysis revealed no negative effects from the music intervention. Clinicians should be aware of the limited utility of music for pain management. Most of the studies in the analysis did not include patients with cancer; however, the highest effect sizes were in the setting of chronic pain, so a music intervention may be relevant to patients with cancer. Use of music along with other nonpharmaceutical and maximal pharmaceutical pain management may be helpful for some patients. Further research in this area would be useful.
Centeno, C., Sanz, A., Cuervo, M.A., Ramos, D., Hernansanz, S., Gonzalez, J., . . . Pascual, A. (2012). Multicentre, double-blind, randomised placebo-controlled clinical trial on the efficacy of methylphenidate on depressive symptoms in advanced cancer patients. BMJ Supportive and Palliative Care, 2, 328–333.
To study the efficacy of methylphenidate for relief of depressive symptoms in patients with advanced cancer.
Patients who indicated some depressive symptoms from screening were randomized to receive methylphenidate ranging from 10-45 mg daily for 28 days. Doses were adjusted according to individual patient need and toxicity evaluation according to a protocol established for the study. Patient visits and evaluation occurred at days 0, 2, 7, 14, 21, and 28 either in the clinic or the patients’ homes. Patients who completed at least eight days of involvement were included in intent-to-treat analysis using the last measure carried forward.
Methylphenidate administration was not significantly better than placebo for symptoms of depression or anxiety and was associated with more adverse events. The evidence regarding efficacy of methylphenidate is inconclusive.
This study sample was not large enough to enable firm conclusions from this individual study; however, findings did not show a benefit of methylphenidate and showed more adverse events that may be associated with methylphenidate. These results are not supportive for use of methylphenidate in the management of anxiety and depressive symptoms in patients with advanced cancer.
Centeno, C., & Vara, F. (2005). Intermittent subcutaneous methadone administration in the management of cancer pain. Journal of Pain and Palliative Care Pharmacotherapy, 19(2), 7–12.
To study the dose, level of pain, and toxicity symptoms associated with intermittent subcutaneous methadone injections used to treat cancer pain
Over seven days, patients whose pain was well controlled with oral methadone received subcutaneous methadone via a butterfly needle that was used exclusively for methadone. The conversion ratio, oral methadone to subcutaneous methadone, was 1:1.
Two of 10 patients withdrew because of nonpainful irritation at the injection site. Compared to the methadone doses other patients were taking, these two patients took significantly higher doses: 40–45 mg, either every 8 hours or every 12 hours. All other patients’ doses were 5–25 mg, either every 8 hours or every 12 hours. Eight patients completed the study over seven days. Pain levels went from 3.3 to 3.5 on a 0–10 scale.
Intermittent subcutaneous methadone administration seems to be a useful alternative when oral administration is not feasible.
The study had a small sample size.
The conversion ratio, oral to subcutaneous methadone, was 1:1. This is not the currently recommended conversion ratio, though patients in the study experienced no increase in toxicity as the result of the 1:1 conversion. However, the duration of the study was only seven days; a longer duration may have resulted in toxicity effects. Higher doses caused local irritation. At even higher doses, clinicians may have to consider other strategies, such as adding dexamethasone to the infusion. If a patient is unable to take oral methadone, alternatives other than subcutaneous methadone—transdermal or buccal administration—are available.
Censabella, S., Claes, S., Robijns, J., Bulens, P., & Mebis, J. (2016). Photobiomodulation for the management of radiation dermatitis: The DERMIS trial, a pilot study of MLS(®) laser therapy in breast cancer patients. Supportive Care in Cancer, 24, 3925–3933.
To assess the effects of Multiwave Lock System low-level laser therapy in the management of acute radiation dermatitis
All patients received standard skin care including hydroactive colloid gel thre times daily throughout radiation therapy and self-adhesive silicone foam dressing for dry or moist desquamation. Those in the laser therapy group also received six sessions twice a week starting from fraction 20 of radiation. Results from the laser group were compared to that of a historical control group who had only usual care.
PHASE OF CARE: Active antitumor treatment
Prospective, quasiexperimental with historical control comparison
RTOG scores in the control group increased over time but remained stable in the laser group. The difference between groups was significant (p < 0.005). There were no cases of greater than grade 2 skin toxicity. Analysis of change in RISRA scores showed improvement in subjective scores in the laser group (p = 0.023) and less score increase overall in the laser group (p < 0.03).
This type of low-level laser therapy was shown to be beneficial in reducing the severity of radiodermatitis among women being treated for breast cancer.
The use of low-level laser therapy may have some benefit for the management of radiodermatitis. The promising findings from this study warrant additional well designed research.
Censabella, S., Claes, S., Orlandini, M., Braekers, R., Thijs, H., & Bulens, P. (2014). Retrospective study of radiotherapy-induced skin reactions in breast cancer patients: Reduced incidence of moist desquamation with a hydroactive colloid gel versus dexpanthenol. European Journal of Oncology Nursing, 18, 499–504.
To compare the efficacy of dexpanthenol cream versus hydroactive colloid gel application during breast radiation therapy (RT)
In this retrospective study, one group of patients receiving breast radiotherapy applied dexpanthenol cream three times per day from day 1 through day 12 of radiation. From day 13 to completion, they switched their skin care regimen to hydroactive colloid gel (Flamigel®). The other group of patients with breast cancer applied only dexpanthenol cream three times per day throughout the entire course of radiation. All patients were women with breast cancer who received a total dose of 66 Gy. Skin assessment was performed by oncology nurses using World Health Organization grading criteria for acute skin toxicity. The occurrence and time to onset of moist desquamation were endpoints for this study.
Retrospective study
Patients who used the hydroactive colloid gel preparation experienced moist desquamation significantly later than patients who used only the dexpanthenol cream (p < 0.0001); however, breast size had a higher hazard ratio till time to development for patients using the cream than those using the gel. The incidence of most desquamation was significantly lower in the group using the gel (p < 0.0001). The incidence was highest in women with large breasts.
Patients with breast cancer undergoing radiotherapy may benefit from using a hydroactive colloid gel from the beginning of radiation treatment until the completion of treatment for the prevention of moist desquamation. The strength of this evidence is limited because of this study's design. Women with large breasts were at higher risk for the development of moist desquamation.
When applied three times daily, the use of a hydroactive colloid gel may provide healing benefits for the skin of patients with breast cancer undergoing radiotherapy and decrease the time to onset of moist desquamation.
Celio, L., Frustaci, S., Denaro, A., Buonadonna, A., Ardizzoia, A., Piazza, E., … Italian Trials in Medical Oncology Group. (2010). Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: A randomized, multicenter, phase III trial. Supportive Care in Cancer,19, 1217–1225.
To assess the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) regimens
All patients received a single IV dose of 0.25 mg palonosetron and 8 mg dexamethasone before chemotherapy on day 1. Patients then were randomized to one of two delayed antiemetic regimens: no additional dexamethasone or 8 mg dexamethasone daily on days 2 and 3. Rescue medication of dexamethasone or metoclopramide was allowed as needed. In patient diaries, participants recorded emetic events, use of rescue medication, and maximum nausea experience.
The study was conducted in multiple sites in Italy.
All patients were in active treatment.
This was a randomized, open-label, parallel group trial.
Patients recorded the number and time of emetic episodes, use of rescue medications, maximum nausea in the previous 24 hours, adverse events, and use of concomitant medication in patient diaries.
The following were measured.
Palonosetron plus single-dose dexamethasone administered before common MEC regimens was not as effective as palonosetron plus dexamethasone for three days in the prevention of CINV.
For patients receiving non-AC MEC chemotherapy, and especially male patients, single-dose palonosetron and dexamethasone could be an option, considering side effects from multiday use of dexamethasone. However, as the study suggested, the need for rescue medication was higher in this group compared with the three-day dexamethasone regimen during the delayed phase.
Celio, L., Denaro, A., Agustoni, F., & Bajetta, E. (2012). Palonosetron plus 1-day dexamethasone for the prevention of nausea and vomiting due to moderately emetogenic chemotherapy: Effect of established risk factors on treatment outcome in a phase III trial. The Journal of Supportive Oncology, 10(2), 65–71.
To verify whether the noninferiority hypothesis of a dexamethasone sparing regimen can be demonstrated even after adjustment for known risk factors for developing CINV and to assess the impact of the risk factors studied on antiemetic outcome
Chemotherapy-naïve patients received 0.25 mg IV palonosetron and 8 mg IV dexamethasone on day 1. Patients were randomly assigned to no additional dexamethasone (1 day dexamethasone regimen) or 8 mg oral dexamethasone on days 2–3 (3-day dexa regimen). After chemotherapy, rescue medication, including dexamethasone or metoclopramide, were permitted on an as-needed basis.
The study was conducted at multiple sites (not specified) in Italy.
This was a prespecified, posthoc analysis of a randomized, multicenter, phase III trial.
The analysis confirmed that the palonosetron plus one-day dexamethasone regimen provides a valid treatment option for prevention of CINV in delayed, non-AC-based MEC. However, these findings are not applicable to younger patients undergoing AC-based chemotherapy as the palonosetron plus three-day dexamethasone regimen achieved statistically better nausea control in this population.
Younger patients were mostly women undergoing AC chemotherapy and, primarily, no history of alcohol consumption. A 15% margin was set for the noninferiority analysis, which is still a highly clinically relevant difference.
Administration of palonosetron with single-day dexamethasone could be recommended for the patients undergoing non-AC-based MEC for the control of delayed CINV, considering the side effects of dexamethasone. This was a noninferiority analysis, meaning that researchers accepted a 15% difference in rate of control as no real difference. Nurses need to be aware of the implications of this type of trial and judge whether lack of CINV control in 15% of patients is acceptable. As the study demonstrated, the palonosetron with three-day dexamethasone regimen is still recommended for the control of nausea, especially for younger patients receiving AC-based chemotherapy.
Celio, L., Agustoni, F., Ricchini, F., Dotti, K., Niger, M., & Braud, F.D. (2013). Palonosetron plus dexamethasone in highly emetogenic chemotherapy: Pooled data from two phase III trials. Future Oncology, 9(10), 1451–1458.
To compare the effectiveness of palonosetron combined with dexamethasone versus older antagonist-containing regimens in combination with dexamethasone in patients receiving highly emetogenic chemotherapy (HEC)
In both studies, eligible patients were randomly assigned to receive a single IV dose of palonosetron (0.25 mg or 0.75 mg), or an older antagonist (Zofran® 32 mg or granisetron 3 mg) as a bolus given 30 minutes before initiation of HEC on day 1. Prophylactic dexamethasone (20 or 16 mg IV) was administered before the initiation of chemotherapy on day 1. In the Saito et al. trial, one of the trials summarized by Celio et al., delayed dexamethasone was also given daily on days 2 and 3. The primary endpoint for efficacy was the proportion of patients achieving CR (defined as no emetic episodes and no use of rescue antiemetics). Patients recorded daily emetic events, nausea, and rescue medications for five days after starting chemotherapy.
Pooled analysis of multi-center, double-blind, double-dummy, parallel-group, active-comparator trials
Patient daily diary recording emetic events, severity of nausea, and rescue medication use
The proportion of patients achieving CR was significantly higher with the palonosetron versus the control regimen in the overall five-day study period (49.2% versus 37.3%; p < 0.0001), in the acute phase (73.1% versus 69.7%), as well as in the post hoc analysis for the delayed time period (53.6% versus 41.2%; p < 0.0001). For either time period, the incremental improvement observed with the use of palonosetron was approximately 12 percentage points.
The analysis of data from two pooled studies demonstrates the benefit of palonosetron plus dexamethasone, compared to older 5-HT3 receptor antagonists plus dexamethasone, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in HEC during a five-day study period. It also suggests a benefit of palonosetron on delayed nausea or vomiting.
This study further supports prior data showing that palonosetron with dexamethasone provides improved protection from overall CINV during HEC, as well as in the delayed phase, over older-generation 5-HT3 receptor antagonists.
Celio, L., Bonizzoni, E., De Braud, F., Agustoni, F., & Aapro, M. (2016). Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? Insight from the re-evaluation of two randomized studies. Supportive Care in Cancer, 24, 1025–1034.
To determine the effectiveness of dexamethasone against delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC)
This reanalysis consisted of of two cohorts of chemotherapy-naïve patients who were included in two phase 3, randomized, controlled trails investigating a dexamethasone-sparing regimen. Participants were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC and AC regimens. Patients were divided according to the effectiveness of prophylaxis against acute CINV as either high- (experienced neither vomiting nor moderate-to-severe nausea) or low-risk (experienced vomiting or moderate to severe CINV).
Secondary analysis of two phase 3, randomized, controlled trials
The dexamethasone-sparing regimen (three-day) achieved excellent control of delayed symptoms in patients with no acute CINV and for low-risk patients receiving AC, but it was less effective in patients receiving HEC. Additional dexamethasone doses could be offered selectively.
Patients receiving AC regimens are at an increased risk of experiencing delayed CINV. Some patients might not benefit from a dexamethasone-sparing antiemetic regimen. In this study, the reduction of dexamethasone was less effective for patients at a high risk. Extending the use of dexamethasone could produce adverse effects, so selective dexamethasone prescriptions should be individualized.