Lucchese, A., Matarese, G., Ghislanzoni, L.H., Gastaldi, G., Manuelli, M., & Gherlone, E. (2016). Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia. Leukemia and Lymphoma, 57, 820–827.
To study the efficacy of palifermin for prophylaxis of OM in pediatric patients undergoing hematopoetic cell transplant (HCT)
Patients were randomly assigned to receive either IV palifermin 60 mcg/kg per day starting three days prior to transplant conditioning chemotherapy or placebo. All patients received basic oral hygiene and invasive nutrition as needed. All other aspects of care were essentially the same between groups. OM was assessed daily from 7 days prior to transplantation to 28 days after transplantation. Assessment was conducted by the same clinician.
Significantly fewer patients in the palifermin group developed grade 2 (p = 0.038) and grade 4 (p = 0.006) mucositis compared to the placebo group. Grade 4 was seen in 11% of patients in the palifermin group and 59% of patients in the control group. Fewer patients in the palifermin group had any grade mucositis, but not all differences in grades were statistically significant. The duration of grade 3 and 4 OM in patients in the palifermin group was three days compared to eight days in the control group (p < 0.001). The only adverse reactions reported were rashes and altered taste, lasting for 48–72 hours. The cumulative morphine daily dose per body weight was lower in the palifermin group (p = 0.04).
Palifermin was shown to effectively reduce the severity, prevalence, and duration of OM among pediatric patients undergoing HCT and was not associated with any significant adverse effects.
Palifermin was shown to be beneficial to pediatric patients undergoing HCT for primary prophylaxis for OM. OM is one of the most painful and debilitating effects of high-dose myeloablative chemotherapy. Nurses can advocate for the consideration of palifermin in these patients. Additional research in support of these findings is warranted, and research regarding the potential role of palifermin in other types of chemotherapy regimens associated with OM is needed.
Lu, W., Matulonis, U.A., Doherty-Gilman, A., Lee, H., Dean-Clower, E., Rosulek, A., . . . Penson, R.T. (2009). Acupuncture for chemotherapy-induced neutropenia in patients with gynecologic malignancies: A pilot randomized, sham-controlled clinical trial. Journal of Alternative and Complementary Medicine, 15, 745–753.
The purpose of the study is to investigate the use of acupuncture during chemotherapy on white blood cell count, absolute neutrophil count, and endogenous G-CSF level.
Patients were randomly assigned to receive acupuncture or sham acupuncture sessions 2–3 times weekly beginning one week prior to chemotherapy cycle 2 and ending at the beginning of cycle 3 of chemotherapy. A standard acupuncture protocol was administered by five different experienced providers. An electroacupuncture machine was connected to needles and a heat lamp was placed above the feet of the patient. Lab work was obtained at baseline, the nadir of cycle 1 and then every seven days during the study period.
Multiple sites in New England
Active antitumor treatment
Double-blind, randomized, placebo-controlled trial
Five patients withdrew from the trial due to disease progression, side effects of chemotherapy, or time commitment. After patients received six acupuncture sessions, there was a significant different in white blood cell counts between groups in favor of acupuncture (p = 0.04). These differences remained at nadir and the second recovery day. Average absolute neutrophil counts (ANCs) were higher in the acupuncture group at several time points, but this difference was not statistically significant. G-CSF levels in the acupuncture group were about four times higher; however, this difference between groups was not statistically significant.
Acupuncture may be helpful in in patients receiving myelosuppressive chemotherapy in reducing neutropenia and associated problems. More definitive study in this area is needed to better evaluate the clinical efficacy of acupuncture in this area
Study findings suggest some promise for use of acupuncture among strategies for the prevention of infection; however, due to the very small sample size, no firm conclusions can be drawn. Issues seen in this study point to the problem of time and frequent travel for patients involved in cancer treatment to participate in this type of intervention. Further research in the use of acupuncture with larger trials is needed for further evaluation of efficacy.
Lu, Q., Zheng, D., Young, L., Kagawa-Singer, M., & Loh, A. (2012). A pilot study of expressive writing intervention among Chinese-speaking breast cancer survivors. Health Psychology, 31, 548–551.
To test the feasibility, cultural sensitivity, and effect of an expressive writing intervention.
Patients completed baseline assessments by mail and received three envelopes that were to be opened according to labels for study week. They were asked to write about their deepest feelings about having cancer and about the strategies they used for coping. They were to write for 20 minutes each week. After the last writing assignment and three and six months later they completed study questionnaires by mail. Focus group interviews were also conducted.
The study used a quasiexperimental, pre-/post repeated measures design.
At three months, the change in fatigue showed a partial eta2 of 0.066, and eta2 for posttraumatic stress was 0.208. There was 100% compliance in completing writing assignments. Patients commented that the activity was meaningful for Chinese women.
Findings suggested that expressive writing is a feasible and acceptable intervention for Chinese American women.
Expressive writing appeared to be an acceptable intervention for these women. The study design and sample size did not allow for any firm conclusions about effects to be drawn.
Low, C. A., Stanton, A. L., Bower, J. E., & Gyllenhammer, L. (2010). A randomized controlled trial of emotionally expressive writing for women with metastatic breast cancer. Health Psychology, 29, 460–466.
To test the effect of emotionally expressive writing in a randomized, controlled trial of patients with metastatic breast cancer (MBC) and to determine whether the effects of the intervention varied as a function of perceived social support or time since metastatic diagnosis.
The sample was recruited from several sources; all contact occurred via telephone, mail, or email. Patients were randomized to either an emotional or control writing condition and were mailed a packet of sealed envelopes. Trained research assistants telephoned women at the beginning of each of the four writing sessions within a three-week interval to read instructions and called back 20 minutes later to ask the women to stop writing. The women mailed the essays to the research office at the end of each session for analysis. Outcomes were measured three months after the final writing.
The study was a randomized, controlled trial.
No significant differences existed between the two experimental conditions on demographic/medical variables, depression, intrusive thoughts, or sleep disturbances. There were no main effects for the experimental condition to predict intrusive thoughts. Perceived emotional support at study entry interacted with the experimental condition to predict IES-Intrusion (F [1, 56] = 11.61; p = 0.001). For women with a decreased level of emotional support at entry, the effect of the experimental condition was significant (p = 0.002). There was no effect on sleep in newly diagnosed patients but increased sleep disturbances for women who had been diagnosed more than 4.7 years.
Contrary to the hypothesis, expressive writing did not reduce psychological distress or improve physical health as quantified by fewer sleep disturbances and somatic symptoms.
Expressive writing may be helpful for a subset of patients with MBC (those with low levels of social support and recently diagnosed) and contraindicated for others (those living longer with the diagnosis). Further studies should explore alternative writing topics, such as perceived benefits of the cancer experience.
Low, C.A., Stanton, A.L., Bower, J.E., & Gyllenhammer, L. (2010). A randomized controlled trial of emotionally expressive writing for women with metastatic breast cancer. Health Psychology, 29(4), 460–466.
To test the effects of emotionally expressive writing versus disease-related writing on patients with metastatic breast cancer; to determine whether the effects of expressive writing vary as a function of perceived social support or time since diagnosis of metastasis
Investigators used three sources of recruitment: a larger study, flyers, and advertising on a website and Listserv. All contact with patients was via telephone, postal mail, or email. Participants completed baseline assessments, which gathered data about demographics and emotional support. Investigators collected saliva samples. Patients were randomized to either the emotional or control writing condition, and patients received information about the exercises. Patients were scheduled to participate in four 20-minute sessions that occurred at patients' convenience within a three-week interval. A research assistant monitored compliance. After each session, a patient mailed her writing to the research office. At study entry and three months after the final writing session, a by-mail questionnaire measured outcomes according to stated instruments.
Randomized controlled trial
Expressive writing did not produce reduction in psychological distress or improvement in physical health. The intervention may be beneficial for a subset of patients with metastasis and contraindicated for other patients.
Expressive writing may be of benefit to a certain subset of patients. The intervention is cost-effective and an activity that patients with low levels of social support can do. Future study should apply the expressive-writing approach to vulnerable, underserved, and understudied populations and offer broader topics for expressive writing (e.g., benefits of the cancer experience, a topic unrelated to cancer). Investigators should provide writing supplies. Future research should consider privacy protections (possibly from family members), especially in cultures that place great value on the privacy of written material.
Lower, E. E., Fleishman, S., Cooper, A., Zeldis, J., Faleck, H., Yu, Z., & Manning, D. (2009). Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. Journal of Pain and Symptom Management, 38, 650–662.
To test the hypothesis that d-methylphenidate (d-MPH) would produce a significant reduction in fatigue compared to placebo.
Patients were randomized to receive the study drug or an identical appearing placebo; packaging and labeling were done by a pharmacist not involved in other aspects of the study. Patients received 5 mg of the drug twice daily by mouth. Measures were performed at baseline and at weeks 1 and 8, which was the end of the double-blind treatment phase. Weekly dose modifications were performed at the investigators' discretion based on the magnitude and duration of response assessed weekly by Clinical Global Improvement–Impression (CGI-I) scores. The maximum allowable total daily dosage was 50 mg/day in two to three doses per day.
This was a double-blind, randomized, controlled study.
D-MPH–treated patients had lower ECOG performance status scores than placebo-treated patients (p = 0.03), indicating better performance. The mean highest dose achieved in d-MPH–treated patients was 27.7 mg/day (range 10–70). A significantly greater improvement in FACIT scores from baseline was seen in patients who received d-MPH compared to placebo at week 8 (p = 0.02). In the study group, there was a mean 10.5-point score reduction in the d-MPH group. Reduction in fatigue was seen at an average dose of 27.7 mg/day of the study drug. All patients had reduction in CGI scores, indicating decreased severity of symptoms from baseline to week 8. Improvement in these scores was seen in a significantly greater percentage of those given d-MPH (p = 0.02). The most frequent adverse events were headache, nausea, and dry mouth in the treatment group and headache, diarrhea, and insomnia in the placebo group. There was a higher rate of adverse events in the d-MPH group. Eleven percent of the treatment group experienced serious adverse events that led to study discontinuation. Events that led to discontinuation were nausea, vomiting, feeling jittery, and abnormal electrocardiogram.
D-MPH treatment in an individualized dosing regimen based on therapeutic response and side effects was associated with a significant improvement in fatigue.
Future studies need to be performed that address a broader range of patient types. The effectiveness of d-MPH in combination with other interventions, such as exercise, should be examined.
Lower, E. E., Fleishman, S., Cooper, A., Zeldis, J., Faleck, H., Yu, Z., & Manning, D. (2009). Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: A randomized clinical trial. Journal of Pain and Symptom Management, 38(5), 650–662.
The study's primary aim was to evaluate the potential therapeutic effect and safety of dexmethylphenidate (d-MPH) in the treatment of patients with chemotherapy-related fatigue. Its secondary aim was to examine the impact of d-MPH on cognitive functioning.
Participants were randomized to a placebo group or an intervention group receiving 5 mg of d-MPH twice daily (10 mg/day total).
The study took place across 24 academic and community-based cancer centers.
This was a randomized, double-blind, placebo-controlled, parallel-group study.
Cognitive measures were taken with the
Other measures were taken with the
The primary outcome of focus was fatigue. Participants treated with d-MPH had significant improvement in fatigue symptoms at week 8 on the FACIT-F (p = 0.02) and on the CGI-S (p = 0.02). The d-MPH treatment group had higher drug-related events (63% vs. 28%) and greater discontinuation of medication (11% vs. 1.3%) than the placebo group. Cognitive function was not significantly improved.
d-MPH can be of benefit in the treatment of fatigue. However, results do not support d-MPH-mediated reduction in cognitive impairment in adult patients with cancer after chemotherapy.
Lowenstein, O., Leyendecker, P., Hopp, M., Schutter, U., Rogers, P.D., Uhl, R., . . . Reimer, K. (2009). Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: A randomised controlled trial. Expert Opinion on Pharmacotherapy, 10, 531-543.
To show the addition of naloxone improves constipation symptoms in patients with non-malignant pain receiving high-dose oxycodone prolonged release (PR).
Patients were randomized to receive either oxycodone PR and naloxone PR or oxycodone PR plus matched oxycodone PR/naloxone placebo. Patients had oxycodone PR titrated to an effective analgesic dose over a 7- to 28-day period and were converted to the study laxative, bisacodyl. Oxycodone immediate release was used as pain rescue medication. Patients were eligible to participate in a 52-week open-label extension. Mean pain over the past 24 hours and bowel function were measured at each study visit and in patient diaries on a daily basis.
This was a double-blind, placebo-controlled, randomized study with an extension phase.
Oxycodone PR/naloxone PR was superior to oxycodone PR at improving bowel function and symptoms of constipation. That improvement was achieved without affecting the analgesic efficacy of the oxycodone component.
The combination of oxycodone PR/naloxone PR in patients with cancer warrants investigation to determine potential benefits in reducing opioid-induced constipation in this population.
Loven, D., Levavi, H., Sabach, G., Zart, R., Andras, M., Fishman, A., . . . Gadoth, N. (2009). Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel. European Journal of Cancer Care, 18, 78–83.
The focus of the study was to evaluate the role of glutamate supplementation in preventing paclitaxel-induced peripheral neuropathy.
Patients were randomized to receive daily placebo or 500 mg glutamate supplementation beginning on the first day of chemotherapy. Treatment was continued throughout six cycles of chemotherapy and for an additional three weeks. Patients were assessed for neuropathy with serial electro-diagnostic measurements at baseline and at the end of the study.
The total sample consisted of 43 women with a median age of 59 years (range of 35–80 years) who were diagnosed with gynecologic cancers and were receiving paclitaxel.
The study was conducted in multiple outpatient sites throughout Israel.
Phase of care
The study had a double-blind, placebo-controlled randomized trial design.
An indication of peripheral neuropathic toxicity was lower in patients receiving glutamate, but the difference was not statistically significant. However, significantly lower pain levels were noted in the glutamate group (p = 0.011). No differences were found between groups regarding electro-diagnostic measurements.
The study does not provide strong support for the benefit of glutamate in the prevention of peripheral neuropathy in patients receiving paclitaxel. No firm conclusions can be drawn due to study limitations.
The findings suggest that glutamate does not prevent peripheral neuropathy during treatment with paclitaxel. Conclusions are limited due to study deficiencies.
Lovell, M.R., Forder, P.M., Stockler, M.R., Butow, P., Briganti, E.M., Chye, R., . . . Boyle, F.M. (2010). A randomized controlled trial of a standardized educational intervention for patients with cancer pain. Journal of Pain and Symptom Management, 40(1), 49–59.
To determine if an educational video and/or booklet for people with advanced cancer and pain can improve pain management and quality of life and decrease anxiety, pain, and pain interference
Patients were recruited from multiple oncology and palliative care clinics and were randomly allocated to one of four treatment groups. Patients in group 1 received standard care only. Those in group 2 received standard care plus a booklet. In group 3, patients received standard care plus a video. Group 4 patients received standard care plus a booklet and video. The video depicted patients, a caregiver, and health professionals talking about cancer pain and management. The booklet, published by the New South Wales Cancer Council, contained text and cartoons about pain and its management. Text was written for a reading age of 12 years. Patient assessment was done at baseline and at weeks 2 and 4 after study entry.
Randomized controlled trial
Barriers were low in all groups at baseline. The barriers scores dropped more in the intervention groups than in the control group, but differences from control or between the other three groups were not significant. There was a significant difference (p < 0.05) in the addiction subscale change in the booklet-only and video-only groups. Authors reported a significantly higher change in average pain (p = 0.0214) between the control and video-and-booklet groups. Authors noted marginal differences in average pain between groups in all other combinations. Reduction in worst pain was significantly greater (p = 0.05) in the video-and-booklet group than in the control group. The size of the differences was small (–1.12). Authors noted no other between-group differences. The presence of a partner increased the effect of any intervention on outcomes (p = 0.004, p < 0.01). According to the pain management index, there was no difference between groups in regard to pain management. Authors observed no difference between groups in regard to anxiety or depression, and they observed no significant change in anxiety or depression. All groups reduced overall consumption of opioids.
In this study a self-administered educational intervention consisting of a booklet and video was associated with a reduction in average pain, worst pain, and fear of addiction.
Findings suggest that standardized education that includes a video and booklet can be helpful in pain management. The effectiveness of the intervention is due, presumably, to greater patient and caregiver involvement in pain management. This study showed that the combination of a booklet and video, along with standard care, was the most effective intervention. The content of each may have reinforced the other. Use of a standardized set of educational materials, such as those used in this study, can be a practical, efficient way to supplement other interventions to manage pain, may be effective in involving patients more directly in pain management, and may help to remove barriers to and misconceptions about pain management.