Schwartzberg, L., Barbour, S.Y., Morrow, G.R., Ballinari, G., Thorn, M.D., & Cox, D. (2013). Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV). Supportive Care in Cancer, 22(2), 469–477.
To determine the safety and efficacy of palonosetron versus older 5-HT3 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)
CR rates were significantly higher for patients who received palonosetron during the delayed (p < 0.0001) and overall (p < 0.0001) phases. There was a greater likelihood for patients who received palonosetron to achieve a CR in the delayed (OR, 1.62 [1.40–1.88]) and overall (OR, 1.56 [1.34–1.81]) phases. CC rates were significantly higher in patients who received palonosetron in the delayed (p < 0.0001) and overall (p < 0.001) phases. No differences in CR or CC were seen between groups in the acute phase. There was a significant difference in the number of emetic episodes in patients who received palonosetron in the acute (p = 0.007), delayed (p < 0.0001), and overall (p < 0.0001) phases. Significant differences were seen in the severity of nausea in the delayed (p = 0.0002) and overall (p = 0.011) phases.
Palonosetron is more effective at achieving CR and CC for CINV in the delayed and overall phases when compared to older 5-HT3 receptor antagonists. Palonosetron is also more effective at reducing the severity of nausea experienced in the delayed and overall phases after chemotherapy. However, in the acute phase, palonosetron is not more effective at controlling CINV compared to older 5-HT3 receptor antagonists.
For patients receiving MEC or HEC, the use of palonosetron rather than an older 5-HT3 receptor antagonist is more effective at controlling CINV in the delayed and overall phase after chemotherapy.
Schwartzberg, L.S., Modiano, M.R., Rapoport, B.L., Chasen, M.R., Gridelli, C., Urban, L., . . . Schnadig, I.D. (2015). Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: A randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncology, 16, 1071–1078.
To assess rolapitant in combination with a serotonin receptor antagonist and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer after the administration of moderately emetogenic chemotherapy (MEC) or regimens containing an anthracycline and cyclophosphamide
Patients received either one oral dose of 180 mg rolapitant or a placebo 1–2 hours before chemotherapy on day 1. All patients received 2 mg granisetron plus 20 mg dexamethasone approximately 30 minutes prior to chemotherapy. Granisetron (2 mg) was also given once daily on days 2 and 3. Additional medications, such as dexamethasone for taxanes, were administered as needed and according to package instructions. Cycles were a minimum of 14 days, and patients received the same regimen (rolapitant or placebo) for up to five subsequent cycles during the study.
Efficacy was measured as a complete response (CR) or no emesis or use of rescue medications as reported in a daily patient journal for up to 120 hours post chemotherapy. Responses were stratified into acute (< 24 hours) and delayed (> 24 hours) phases. Also, the Functional Living Index-Emesis (FLIE) survey was used to measure the effect of nausea or vomiting on daily living. The FLIE uses a seven-point visual analog scale (VAS) on nine questions to assess patients on day 6 of cycle 1. Finally, safety variables (e.g., adverse reactions) were assessed and reported.
The findings showed that a significantly greater proportion of patients receiving rolapitant had CRs in the delayed phase than those who received the active control (95% CI [1.2, 2.0], p = 0.0002). No significance was found in the acute phase between patients receiving rolapitant and the control. Adverse events were similar between groups with the most frequent events being fatigue, constipation, and headache. In cycle 1, grade 3–4 neutropenia was 5% in the rolapitant group and 3% in the active control group.
The findings showed that rolapitant in combination with a 5-HT3 and dexamethasone was well tolerated and showed superiority over active control for the prevention of CINV during the five-day (0–120 hour) at-risk period after the administration of MEC or drug regimens containing an anthracycline.
Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone was well tolerated by this sample and demonstrated acceptable extended (0–120 hours) control of CINV associated with MEC regimens and regimens containing an anthracycline and cyclophosphamide.
Schwartz, A. L., Thompson, J. A., & Masood, N. (2002). Interferon-induced fatigue in patients with melanoma: a pilot study of exercise and methylphenidate. Oncology Nursing Forum, 29, E85–E90.
Patients took methylphenidate 20 mg sustained release every morning and followed an aerobic exercise program for 15 to 30 minutes four days a week. Aerobic exercise is hypothesized to decrease fatigue by improving physical conditioning and mental concentration.
This was an open-label pilot study with comparison to historic controls.
All patients adhered (as determined by patient diaries) to the exercise portion of the intervention over the four months of the study. Four of 12 patients were unable to adhere to methylphenidate: three refused to continue on methylphenidate beyond the first 48 hours of the study (reasons for discontinuation included indigestion, mild nervousness, and unwillingness to take more pills), and one had methylphenidate discontinued by the investigators due to marked anxiety. Patients receiving exercise and methylphenidate or exercise alone experienced lower fatigue levels compared to historic controls. Patients who exercised and took methylphenidate reported the lowest levels of fatigue. The exercise-only group experienced a greater decline in cognitive function when compared with patients who exercised and took methylphenidate. Patients in the in exercise and methylphenidate group lost 8.1 kg, and those in the exercise-only group lost 8.2 kg.
Special training or consultation may be required to prescribe an exercise program for patients with cancer. Cost is related to drug acquisition.
Schwartz, A.L., Thompson, J.A., & Masood, N. (2002). Interferon-induced fatigue in patients with melanoma: A pilot study of exercise and methylphenidate. Oncology Nursing Forum, 29(7), E85–E90.
This study was conducted to examine the effect of exercise and methylphenidate (MPH) on fatigue, functional ability, and cognitive function in patients with melanoma. It also aimed to determine the percentage of patients who adhered to interferon-alfa, MPH, and exercise treatment.
The intervention group was given 20 mg of long-acting MPH every morning for four months and took part in at least 15–20 minutes of aerobic exercise four days per week. The duration and intensity of exercise gradually increased over the study's four months.
Assessments were completed prior to the first dose of interferon-alfa. Subsequent assessments of functional ability and cognition function (using Trail Making Test forms) and quality of life were repeated at one and four months after baseline. Subsequent assessments of fatigue scale, body weight, daily activity, and medication logs were submitted monthly.
The study took place at a university-based cancer center.
This was a longitudinal pilot study with descriptive/exploratory design. It made use of a historic control group for comparison.
Functional ability increased an average of 6% for all participants and 9% for the treatment group. A percent change in a 12-minute walk was negatively related to TMT-A (p = 0.04) and TMT-B (p = 0.05), suggesting a relationship between higher exercise and improved cognitive functioning (indicated by lower scores on TMT). Taking MPH was correlated with improved TMT-B performance at 4 months (r = -0.85, p < 0.001).
All participants' cognitive function scores were within normal ranges at baseline. Sixty-six percent of participants adhered to MPH at four months; all subjects continued to exercise at four months.
The combination of exercise and MPH has positive effects on cognitive function, functional ability, and fatigue over time. The authors suggest that MPH may have contributed to better exercise adherence.
Schuurs, A., & Green, H.J. (2012). A feasibility study of group cognitive rehabilitation for cancer survivors: Enhancing cognitive function and quality of life. Psycho-Oncology. [e-pub ahead of print].
The intervention, based on self-regulatory cognitive rehabilitation and cognitive behavioral principles, consisted of four weekly two-hour group sessions with between-session homework. Each session consisted of psycho-education, group discussion, and reinforcement of the content by skill development and application. Subject matter included overall information on cognition with specific information on memory, attention, and the impact of fatigue and emotions on cognition. Application exercises focused on goal setting, problem solving, relaxation, compensatory and enhancement strategies, and cognitive-behavioral strategies related to emotional adjustment, fatigue, sleep, and self-care.
All participants receiving the intervention were assessed at baseline, post-treatment (six weeks after the baseline assessment), and follow-up (three months after the second assessment). Study participants not receiving the intervention were assessed at similar time frames but only for the first two time periods.
The clinical application is for late effects and survivorship.
The study consisted of a controlled trial with repeated measures.
In contrast to the cancer and community comparison groups, the intervention group had a significant improvement in immediate memory (p < 0.01), visuospatial skill (p < 0.001), language (p < 0.001), attention/concentration (p < 0.05), delayed memory (p < 0.001), and total cognitive score (p < 0.001) over the six-week time interval as measured by the RBANS. No change was found in either information processing speed as measured by the TMT-A or executive function as measured by the TMT-B.
The intervention group was re-evaluated three months later; improvements remained, or were sustained, in immediate memory (p < 0.001), visuospatial skill (p < 0.001), delayed memory (p < 0.001), and total cognitive score (p < 0.001), but not in language or attention/concentration. At the final assessment, a significant improvement was also found on the TMT-A (p < 0.01). Although no change was found in self-report of cognitive function as measured by the MASQ, a significant improvement was found over time as measured by the FACT-Cog (p < 0.05).
Significant improvement was found in several cognitive domains for patients who received the group intervention. Many of these improvements were sustained three months after the completion of the intervention. The results of the subjective measures of cognitive function were mixed. This study found that a short group intervention may improve cognitive ability for cancer survivors over a limited period of time.
Further research is indicated, with larger sample sizes and longer follow-up, to determine whether group cognitive rehabilitation might be warranted to treat cognitive impairments. More detailed information regarding the intervention is needed to determine whether it could be facilitated by nurses rather than the clinical psychologists in the study.
Schutter, U., Grunert, S., Meyer, C., Schmidt, T., & Nolte, T. (2010). Innovative pain therapy with a fixed combination of prolonged-release oxycodone/naloxone: A large observational study under conditions of daily practice. Current Medical Research and Opinion, 26, 1377–1387.
To evaluate the safety and efficacy of combined prolonged-release (PR) oxycodone and PR naloxone for treatment of cancer-related pain in daily practice
Patients with severe chronic pain requiring strong analgesics entered a four-week observational period, during which they received PR oxycodone–PR naloxone. The physician determined dosage. Dose adjustments, comedication, rescue medication, and other treatments were also at the discretion of the physician. Follow-up visits occurred after the first week and at the end of the four-week observation. Data were gathered using interviewer-administered questionnaires.
Observational
PR oxycodone–PR naloxone was associated with effective analgesia and reduction in symptoms of opioid-induced bowel dysfunction. This combination was associated with minimal adverse events.
The fixed combination of PR oxycodone–PR naloxone may be effective in managing chronic pain and cause few problems, such as constipation, which opioids typically cause.
Schumacher, K., Schneider, B., Reich, G., Stiefel, T., Stoll, G., Bock, P. R., . . . Beuth, J. (2003). Influence of postoperative complementary treatment with lectin-standardized mistletoe extract on breast cancer patients. A controlled epidemiological multicentric retrolective cohort study. Anticancer Research, 23, 5081–5087.
Data were retrieved by investigators from the patients’ medical records at each of the study centers and were transferred to a standardized case report form (CRF). Data collected included patient demographics, characteristics of the tumor disease, treatments, signs, symptoms, side effects experienced by patients, and the course of the disease. For each symptom, a patient was included in the analysis if the symptom was present either at the beginning and/or the end of postoperative treatment, and if an assessment was available for both time points. The primary target criterion was the change in symptom score between the start and end of postoperative treatment.
The study included seven study centers randomly identified in Germany (hospitals and general or specialized practitioners).
Patients were undergoing the active treatment phase of care.
This was a controlled, epidemiologic, multicentric, retrolective, cohort study with parallel groups.
Data were collected on CRFs in which, prior to data collection, the data elements required for the study were identified and defined.
The mean change in fatigue symptom scores during the postoperative study period was significantly larger (beneficial) in the therapy group compared to the control group (p < 0.0001). The adjusted odds ratios for fatigue in treatment/control was 7.33. A multivariate analysis of the combined symptom score was calculated in accordance to Wei-Lachin and proved a significant superiority of the therapy group (p = 0.0001).
Schuler, M.K., Hentschel, L., Kisel, W., Kramer, M., Lenz, F., Hornemann, B., . . . Kroschinsky, F. (2016). Impact of different exercise programs on severe fatigue in patients undergoing anticancer treatment-A randomized controlled trial. Journal of Pain and Symptom Management, 53, 57–66.
To compare partially supervised, structured exercise to standard of care for patients with advanced cancer. The primary outcome was general fatigue.
Patients were randomized into three groups. Group A received treatment as usual; participants in group B were taught a structured, individual sports program; and group C received additional ambulatory physiotherapeutical supervision. Exercises were defined based on expert consensus with physical therapists and physicians. Included as “possible exercises” into a catalog and a patient information sheet. For groups B and C, a physical therapist selected applicable exercises from this catalog. Patients were instructed to complete three sessions of endurance and two sessions of strength each week for 20-30 minutes per session. Patients were contacted at weeks 4 and 8, during which groups B and C could ask specific questions and adherence was encouraged. Patients were then followed up with in person at 12 and 24 weeks.
PHASE OF CARE: Active antitumor treatment
Randomized, controlled trial into three groups
No difference in general fatigue was observed. Significant difference was found with mental fatigue (p = 0.03). Over time, all groups experienced an increase in fitness, with group C experiencing the most improvement.
No effects on fatigue were seen.
This study did not find any effect of interventions. The study was underpowered to identify significant differences between groups.
Schubert, M.M., Eduardo, F.P., Guthrie, K.A., Franquin, J., Bensadoun, R.J., Migliorati, C.A., et al. (2007). A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Supportive Care in Cancer, 15(10), 1145–1154.
Low level laser therapy (LLLT) using two different low level GaAIAs diode lasers was administered 650 nm to group I and 780 nm to group II compared to sham treatment in the placebo group (group III) beginning on the first day of conditioning and continuing through two days after HCT.
Assessors and patients were blinded; only the laser therapist knew the treatment type.
Powered for 22 subjects per group
70 patients were treated on protocol.
Group 1: n = 23
Group 2: n = 24
Group 3: n = 24
The median age was 44–48 years (range = 18–69 years).
Autologous versus allogeneic was 17% versus 82% in group I, 9% versus 90% in group 2, and 8% versus 92% in group III.
February-November 2001
Randomized, double-blind, placebo-controlled study of patients with HCT
Oral mucositis index OMI and VAS for pain
0, 4, 7, 11, 14, 18, 21
State mean OMI scores varied most at day 11. Scores approached significance (p = 0.06 not significant) when adjusted. Patient-specific average OMI scores for TBI were p = 0.03 (group I) and p = 0.23 (group II).
Two patients died with severe mucositis.
Patients in the placebo group appeared to have suffered more pain than patients in the laser treatment group, particularly group I.
The study demonstrated a tendency for LLLT to reduce severity of mucositis during the second week.
Pain data were incomplete; some patients were too ill to do VAS.
Although randomly assigned, TBI and busulfan/cytoxan were not equally distributed.
Small sample size
Set up as a prevention trial, so treatment only occurred through day 2.
Schrenk, K.G., Schnetzke, U., Stegemann, K., von Lilienfeld-Toal, M., Hochhaus, A., & Scholl, S. (2015). Efficacy of antifungal prophylaxis with oral suspension posaconazole during induction chemotherapy of acute myeloid leukemia. Journal of Cancer Research and Clinical Oncology, 141, 1661–1668.
To examine effectiveness of oral suspension posaconazole for antifungal prophylaxis
Consecutive patients were examined retrospectively. All received intensive-induction chemotherapy. All were given oral suspension posaconazole at 200 mg three times daily. All received antibacterial and antiviral prophylaxis. All infectious workups, empiric treatment, and second-line treatment were standard.
Seventy percent did not develop invasive fungal infection during AML induction chemotherapy. Twenty-one percent had possible infection, and one-third underwent empiric first-line antifungal treatment because of persistent fever of unknown origin or presence of pulmonary infiltrates. Fourteen patients with possible infection received either liposomal amphotericin B or caspofungin. Only those receiving caspofungin required second-line antifungal treatment.
A high proportion of patients received consecutive antifungal treatment. Optimal protection against fungal infection in patients with AML undergoing induction chemotherapy is not clear.
Prevention of infection, and invasive fungal infection in particular, is a challenge in patients undergoing induction chemotherapy for AML. Findings from this retrospective review suggest that a high proportion of patients routinely given oral suspension posaconazole required additional treatment for possible invasive fungal infection. The authors noted that there is uncertain bioavailability of posaconazole given as oral suspension, suggesting that evaluation of various formulations is needed, and that this may not be the most effective approach for antifungal prophylaxis.