Gosselin, T.K., Schneider, S.M., Plambeck, M.A., & Rowe, K. (2010). A prospective randomized, placebo-controlled skin care study in women diagnosed with breast cancer undergoing radiation therapy. Oncology Nursing Forum, 37(5), 619–626.
To compare the effectiveness of three different products in reducing incidence of radiodermatitis
Women were randomly assigned to placebo (sterile water mist), Aquaphor, Biafine or RadiaCare gel. Patients were instructed to apply the product two times daily with the start of radiotherapy and until treatment was complete. Patients were not to use any other skin care product on the affected area. The radiation nurse assessed patients weekly and reminded them to complete home journals. The investigators conducted independent skin assessments on a random sample of 10% of patients to establish reliability of observations.
The study took place in an outpatient setting at Duke University.
Patients were undergoing active antitumor treatment.
The study used a double-blind placebo-controlled randomized four-group trial design.
Ninety-five percent of patients had a skin reaction, with most occurring by week 4. None of the products tested showed a significant difference to reduce the incidence of grade 2–4 skin toxicity compared to placebo. Increases in the proportion with a skin reaction were greatest among those using Biafine. Increases in skin reaction were similar to each other in the other study groups. Patient adherence to use was greater than 80% during the study. Biafine was associated with the greatest increase in toxicity across groups.
None of the products tested here were better than placebo in reducing incidence of grade 2–4 radiodermatitis.
Findings suggest that none of these particular products are effective, although a systematic review and meta-analysis in this area suggest that using anything is more effective than using nothing. Further well-designed research in prevention and management of radiodermatitis is needed.
Gosselin, T. K., Schneider, S. M., Plambeck, M. A., & Rowe, K. (2010). A prospective randomized, placebo-controlled skin care study in women diagnosed with breast cancer undergoing radiation therapy. Oncology Nursing Forum, 37, 619–626.
To compare the effectiveness of three products in reducing the incidence of radiodermatitis.
Women were randomly assigned to placebo (sterile water mist), Aquaphor, Biafine, or radiacare gel. Patients were instructed to apply the product two times daily with the start of radiation therapy (RT) and until treatment was complete. Patients were not to use any other skin care product on the affected area. The radiation nurse assessed patients weekly and reminded them to complete their home journals. The investigators conducted independent skin assessments on a random sample of 10% of patients to establish reliability of the observations.
Patients were undergoing the active antitumor treatment phase of care.
The study was a double-blind, placebo-controlled, randomized, four-group trial.
Of the patients, 95% had a skin reaction, with most occurring by week 4. No product tested showed a significant difference in reducing the incidence of grade 2 to 4 skin toxicity compared to placebo. Increases in the proportion with a skin reaction were greatest among those using Biafine. Increases in skin reactions were similar to each other in the other study groups. Patient adherence to use was greater than 80% during the study.
No product tested was better than placebo in reducing the incidence of grade 2 to 4 radiodermatitis.
Biafine, Aquaphor, and radiacare gel were no more effective than placebo in reducing the incidence of clinically relevant skin toxicity with RT in patients with breast cancer. Biafine was associated with the greatest increase in toxicity across groups. Findings suggested that none of these products are effective, although a systematic review and meta-analysis in this area suggests that using anything is more effective than using nothing. Further well-designed research in prevention and management of radiodermatitis is needed.
Sheinfeld Gorin, S., Krebs, P., Badr, H., Janke, E.A., Jim, H.S., Spring, B., . . . Jacobsen, P.B. (2012). Meta-analysis of psychosocial interventions to reduce pain in patients with cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(5), 539–547.
The search retrieved 1,681 studies published 1996–2010. Three pairs of raters independently reviewed 1,681 abstracts, using an online coding program designed for this project. Studies meeting the inclusion criteria were evaluated for quality according to a modified seven-item coding scheme based on the Physiotherapy Evidence Database. The project leader reviewed findings from rater pairs, resolved discrepancies, and produced a final list of studies for full-text examination. The list of studies was divided among the three pairs of raters.
The weighted average effect size in 38 comparisons for pain severity (k = 38) was 0.34 (95% CI 0.23–0.46; p < 0.001). The weighted average effect size in four comparisons for pain interference was 0.40 (95% CI 0.21–0.60; p < 0.001). Among studies that measured pain severity, skills-based interventions yielded a higher but statistically nonsignificant effect size than did educational approaches (k = 18, g = 0.45 versus k = 19, g = –0.29, respectively; p = 0.22).
Psychosocial interventions decrease cancer-related pain severity and the extent to which pain interferes with activities. Both skills instruction and education approaches can improve the management of cancer pain.
Gore, L., Chawla, S., Petrilli, A., Hemenway, M., Schissel, D., Chua, V., … Adolescent Aprepitant in Cancer Study Group. (2009). Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: A randomized, double-blind, placebo-controlled study of efficacy and tolerability. Pediatric Blood and Cancer, 52, 242–247.
To evaluate the tolerability, efficacy, and pharmacokinetics of aprepitant with a 5-HT3 receptor antagonist and corticosteroid in adolescents with cancer
Patients were randomized to receive either a regimen of aprepitant plus dexamethasone and ondansetron or the control arm of ondansetron and dexamethasone. On the day of chemotherapy, aprepitant or placebo was administered 1 hour before and dexamethasone and ondansetron were given 30 minutes before chemotherapy. Rescue medication was permitted. Patient follow-up was done between days 6 and 8 and between days 19 and 29. Patients recorded episodes of vomiting in diaries for five days following chemotherapy. For the experimental arm, aprepitant was given at 125 mg day 1, 80 mg days 2 and 3, 4 mg day 4; 8 mg dexamethasone day 1, 4 mg days 2 and 3; and ondansetron at 0.15 mg/kg, three times per day on days 1 and 2. In the control arm, patients received 16 mg dexamethasone on day 1, 8 mg on days 2–4, and ondansetron at 0.15 mg/kg, three times per day on days 1 and 2.
The study was conducted at a single outpatient setting at Children’s Hospital, University of Colorado.
The patients were pediatric, in active treatment.
This was a randomized, double-blind, parallel group study.
More patients in the aprepitant group achieved CR for CINV control in the acute and delayed phases, as well as in the overall study period. The addition of aprepitant to the antiemetic regimen appeared to be well tolerated in adolescents, with an overall adverse event profile similar to that seen in adults.
Findings suggest that aprepitant in addition to standard antiemetic treatment is tolerable and may be helpful in patients between the ages of 11 and 19. Further study of the efficacy of antiemetic regimens in the pediatric and adolescent populations is warranted.
Gordon, J.N., Trebble, T.M., Ellis, R.D., Duncan, H.D., Johns, T., & Goggin, P.M. (2005). Thalidomide in the treatment of cancer cachexia: A randomised placebo controlled trial. Gut, 54, 540–545.
To evaluate the safety and efficacy of thalidomide in attenuating weight loss in patients with cachexia secondary to advanced pancreatic cancer
Fifty patients were randomized to receive 200 mg of thalidomide by mouth daily or placebo for 24 weeks. At four weeks, 33 patients were evaluated; at eight weeks, 20 patients were evaluated.
Patients were included in the study if they
Patients were excluded if they
The study was a randomized, placebo-controlled trial.
At four weeks, 33 patients were evaluable. The thalidomide arm gained 0.37 kg in weight and 1 cm3 of arm circumference muscle mass. The placebo arm lost 2.21 kg in weight and 4.46 cm3 of arm circumference muscle mass.
At eight weeks, 20 patients were evaluable. The thalidomide arm lost 0.06 kg in weight and 0.5 cm3 of arm circumference muscle mass. The placebo arm lost 3.62 kg in weight and 8.4 cm3 of arm circumference muscle mass.
Thalidomide was well tolerated and effective at attenuating weight loss and loss of lean body mass. Findings were unable to demonstrate that attenuation in weight loss led to improvement in quality of life.
Good, P., Jackson, K., Brumley, D., & Ashby, M. (2009). Intranasal sufentanil for cancer-associated breakthrough pain. Palliative Medicine, 23(1), 54–58.
To demonstrate the efficacy, safety, and acceptability of intranasal sufentanil as a treatment for cancer-related breakthrough pain (BTP)
Dose titration included three steps. In step 1, a clinician administered 9 mcg sufentanil. Administration was repeated at 10 and 20 minutes, as required. If sufentanil was ineffective at 30 minutes, the clinician administered, the patient's usual BTP opioid. Step 2 comprised actions relating to the next episode of BTP. During this episode, the clinician administered 18 mcg sufentanil, using the same repetition procedure as in step 1. In step 3, during the next episode of BTP, the clinician administered 36 mcg sufentanil, using the same repetition procedure as in step 1. In all steps, pain was assessed at 0, 5, 10, 15, 30, 60, and 120 minutes. In the ongoing phase of the study, in each BTP episode, each patient received the titrated dose that had proven effective.
Prospective, descriptive study
The study showed that intranasal sufentanil has rapid onset and is an effective and safe means of controlling cancer-related BTP.
Sufentanil may be an option for the treatment of BTP; presently, however, its use remains investigational.
Goodwin, J.W., Green, S.J., Moinpour, C.M., Bearden, J.D., III, Giguere, J.K., Jiang, C.S., … Albain, K.S. (2008). Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: southwest oncology group study 9626. Journal of Clinical Oncology, 26, 1650–1656.
Southwest Oncology Group Study 9626 evaluated megestrol for management of menopausal symptoms in women with breast cancer. It compared two doses of megestrol acetate versus placebo over six months. Participants were randomized to placebo, megestrol 20 mg, or megestrol 40 mg daily for three months. If success was achieved, treatment continued for three additional months. If not, the patient was unblinded and given megestrol 20 mg daily.
Participants: 288 patients with T 1-3, N0-1 breast cancer following surgery, chemotherapy, and at least four months of tamoxifen, if prescribed, were enrolled. 225 completed the trial.
This was a phase III, randomized, placebo-controlled, double-blind trial.
At the initial evaluation, patients completed a seven-day patient daily log of hot flashes with re-evaluation at three and six months. The primary endpoint was differences in the probability of hot flash reduction in three comparison groups. Instruments included:
At three months, improvement was 14% with placebo, 65% withmegestrol acetate 20 mg, and 48% with megestrol acetate 40 mg. Both doses were superior to placebo (p < .0001). Duration of effectiveness continued at six months. Megestrol 40 mg was not superior to megestrol 20 mg.
The recommended daily dose is 20 mg.
The study was not designed to evaluate long-term toxicities or relapse of symptoms with long-term use. Concern remains regarding the use of progestins in women with a history of breast cancer.
Gonzalez, A.V., Ullmann, A.J., Almyroudis, N.G., & Segal, B.H. (2008). Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for invasive mold infections: point. Journal of the National Comprehensive Cancer Network, 6, 175–182.
To determine if there is sufficient evidence that pre-emptive antifungal treatment is as effective as antifungal prophylaxis with posaconazole. The patient populations addressed included patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and allogeneic hematopoietic stem cell transplantation (HSCT) recipients with significant graft-versus-host disease.
Prophylactic antifungal therapy is defined as the initiation of an antifungal agent to high-risk patients to prevent a fungal infection. Pre-emptive antifungal therapy is defined as the initiation of antifungal therapy in high-risk patients based on laboratory markers, radiologic monitoring, or both to identify early invasive fungal infections (IFIs) before clinically overt disease develops. The authors based their evaluation on the principle that prophylaxis of fungal infections is important due to the significant morbidity and mortality associated with fungal infections, the incidence in high-risk patients, the safety of available antifungal agents, and the lack of sensitive methods of early detection. A pre-emptive approach is limited by the sensitivity and specificity of available detection methods. The authors reviewed the current literature on posaconazole prophylaxis and pre-emptive antifungal therapy.
No databases used for a search were listed, nor were any inclusion or exclusion criteria mentioned. However, keywords searched were invasive fungal infection, prophylaxis, pre-emptive therapy, and aspergillosis.
One prospective, randomized trial compared posaconazole with fluconazole or itraconazole as a primary antifungal prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia. Proven or probable IFIs occurred in seven (2%) patients in the posaconazole group and 25 (8%) patients in the fluconazole or itraconazole group (p < 0.001). Significantly fewer patients in the posaconazole group had invasive aspergillosis. Survival was improved in posaconazole recipients (p = 0.04). Serious adverse events possibly related to treatment occurred in 6% of patients in the posaconazole group and in 2% in the fluconazole or itraconazole group (p = 0.01).
One prospective, randomized trial compared primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic HSCT recipients with significant graft-versus-host disease on immunosuppression. Posaconazole was at least as effective as fluconazole in preventing IFIs during the prespecified period of observation (incidence, 5.3% versus 9%, respectively; p = 0.07) but was superior in preventing invasive aspergillosis and deaths caused by IFIs. If the analysis was restricted to the period in which patients received the study drug, posaconazole was considered superior to fluconazole in preventing IFIs (incidence, 2.4% versus 7.6%; p = 0.004), particularly invasive aspergillosis (incidence, 1% versus 5.9%; p = 0.001). Treatment-related adverse events were similar between the groups. One peer-reviewed publication reported pre-emptive antifungal therapy. The study was a feasibility study in which a total of 136 treatment episodes for patients with neutropenia at high risk for IFI were screened with daily serum galactomannan testing. There was a diagnostic algorithm that included chest computed tomography (CT) scans and bronchoalveolar lavage. Patients who met prespecified criteria for probable or proven invasive fungal infection received pre-emptive therapy with liposomal amphotericin B; neutropenic fever alone did not trigger modification in the antifungal regimen. Although this approach was successful in identifying early invasive aspergillosis and avoiding amphotericin B use in most patients with persistent neutropenic fever of unknown origin, invasive aspergillosis developed in 17 patients and zygomycosis in one patient among 136 chemotherapy treatment episodes. All cases of invasive aspergillosis were identified through positive antigenemia results. Seven (41%) deaths occurred in patients with positive serum galactomannan results; of these, six had autopsy-proven invasive aspergillosis. However, only two patients were considered to have died directly because of invasive aspergillosis.
The authors believe that insufficient evidence exists to recommend a pre-emptive antifungal therapy approach in place of posaconazole prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and allogeneic hematopoietic cell transplantation (HCT) recipients with significant graft-versus-host disease.
No conflict of interest was stated.
Posaconazole is recommended as a primary antifungal prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and in allogeneic HCT recipients with significant graft-versus-host disease. Pre-emptive treatment is not recommended in these patient populations.
Gonzalez-Barboteo, J., Alentorn, X.G., Manuel, F.A., Candel, V.A., Eito, M.A., Sanchez-Magro, I., . . . Porta-Sales, J. (2014). Effectiveness of opioid rotation in the control of cancer pain: The ROTODOL study. Journal of Opioid Management, 10, 395–403.
To assess the effectiveness of and adverse events associated with opioid rotation for the management of cancer-related pain
All consecutive patients who attended the clinics of participating hospitals were eligible. A single opioid conversion table was used by all participants. If a rotation was used because of pain and toxicity, the baseline dosage was reduced by 25%–50% prior to the change. If no toxicity was present, an equivalent dose was used. Pain was assessed days prior to the implementation of the rotation and one week postimplementation. During the week, changes in opioid dosage were allowed and recorded. Patients were followed for 90 days.
Observational
About 89.5% of patients had one opioid rotation. The most common drugs used for the rotation were morphine, fentanyl, and transdermal buprenorphine. The most common switch was from fentanyl to morphine. The rotation was effective in 75.4% of patients for reducing average pain and in 57.8% for breakthrough pain. Average pain decreased at day 7 (p < 0.001) by four points, breakthrough intensity decreased by four points (p < 0.001), and the number of breakthrough episodes decreased on average from three to one (p < 0.001). Among patients in whom the rotation was effective, there were no significant differences between pre- and postequivalent doses of opioids. In 10 switches (out of a total of 75), there were no toxicities postrotation at one week. Rotations to methadone appeared to be associated with more postrotation adverse events.
The results of this study suggest that opioid rotation can be effective for pain management and the reduction of opioid-associated toxicities in most patients. Rotations to methadone appeared to be associated with more toxicities than rotations to other medications.
In patients with severe cancer-related pain, opioid rotations may be beneficial for improving pain management and addressing opioid-related toxicities. However, the duration of this effect is not clear. These results suggest that switching to methadone might not be the best choice for reducing toxicities.
Gong, S., Sheng, P., Jin, H., He, H., Qi, E., Chen, W., . . . Hou, L. (2014). Effect of methylphenidate in patients with cancer-related fatigue: A systematic review and meta-analysis. PloS One, 9(1), e84391.
To assess the safety and efficacy of methylphenidate for cancer-related fatigue. Secondary outcomes included depression, cognition, and adverse effects.
TYPE OF STUDY: Meta-analysis and systematic review
DATABASES USED: PubMed. EMBASE, PsycINFO, Cochrane Collaboration
KEYWORDS: Methylphenidate, dimethylphenidate, Ritalin, cancer, fatigue, asthenia, tiredness, and randomized controlled trial
INCLUSION CRITERIA: Randomized controlled trials, adults older than 18 years, the trial examined efficacy of methylphenidate on fatigue, and results were sufficient to calculate effect sizes
EXCLUSION CRITERIA: None specified
TOTAL REFERENCES RETRIEVED: N = 374
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Jadad scale was used for quality assessment.
PHASE OF CARE: Multiple phases of care
Meta-analysis was done with studies grouped according to the measure of fatigue that was used. In studies using the FACT-F (three studies), results showed a favorable effect of methylphenidate with a mean difference of -3.13 and a signficant overall effect (p -0.01). In studies using the BFI, results showed a favorable effect with mean difference of -0.69, but the Z test of overall effect was not significant. Methylphenidate had no effect on depression (two studies) or cognitive impairment (two studies). Studies varied widely in terms of the duration of treatment. Treatment for greater than four weeks was superior compared to placebo. However, treatment for less than four weeks did not show a significant effect compared to placebo. Rates of adverse effects between those getting methylphenidate and those getting a placebo were not significantly different. Those receiving methylphenidate had significantly more vertigo, anxiety, and nausea.
Results suggest that treatment with methylphenidate for at least four weeks is effective in reducing cancer-related fatigue and is not associated with a high rate of adverse effects. Treatment with methylphenidate did not improve depression or cognitive impairment. Use of different methods of measurement of fatigue showed different results.
Few studies were included, and some of these had very small sample sizes. Included studies did not provide sufficient information on relevant concomitant conditions of patients, such as sleep disorders and anxiety. Dosages and dosage increase approaches with methylphenidate varied.
Findings suggest that treatment with methylphenidate for at least four weeks can be helpful in managing cancer-related fatigue. However, the most appropriate dosages are not clear. Patients can experience side effects, and if methylphenidate is used, nurses need to monitor patients for side effects. Further large studies are needed to strengthen evidence related to effects and side effects of methylphenidate.