Henke, C.C., Cabri, J., Fricke, L., Pankow, W., Kandilakis, G., Feyer, P.C., & de Wit, M. (2014). Strength and endurance training in the treatment of lung cancer patients in stages IIIA/IIIB/IV. Supportive Care in Cancer, 22, 95–101.
To test the effects of a specially designed strength and endurance training on the independence and quality of life (QOL) in patients with stages III/IV lung cancer while undergoing chemotherapy
Endurance training and breathing techniques were performed five days per week, and strength training was performed every other day while patients received three cycles of inpatient chemotherapy (platinum based). Endurance training consisted of walking and stair exercises. Strength training consisted of four different endurance exercises (trunk stability, leg, arm, and abdominal musculature), as well as breathing techniques (active cycle of breathing) combined with conventional physiotherapy. Control arm received conventional physiotherapy. Evaluations were conducted at baseline and after three cycles of chemotherapy.
PHASE OF CARE: Active anti-tumor treatment
Randomized controlled trial
6 minute walk test, staircase walking (number of steps), Barthel Index (primary outcome measure), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30, Modified Borg Scale
After intervention, the intervention group had a significantly higher Barthel Index (p = 0.003), indicating higher independence with ADLs. In the single scores of the EORTC QLQ-C30, the intervention group reported higher physical functioning (p = 0.025), lower hemoptysis (p = 0.019), lower pain in the arms/shoulders (p = 0.048), peripheral neuropathy (p = 0.05) and cognitive functioning (p = 0.05). There were significant differences in ability on 6 minute walk test and stair walking as well as strength capacity (all p < 0.05). The level of dyspnea decreased significantly in the intervention group while performing submaximal walking activities.
This study shows both feasibility and effects of a strength and endurance program during chemotherapy for lung cancer. The effects were significantly positive for the intervention group in every area (strength, endurance, QOL, independence). There were many issues with the study, however, making it difficult to apply to other populations. One huge issue is that it is unclear how many of the patients were SCLC versus NSCLC. These populations would have a wide difference in the natural history of disease on platinum regimen for the first few cycles; therefore, not knowing the content of each group is problematic. There were also large differences at baseline, so the effects are harder to evaluate. There was a very small sample size and large dropout rate. The intervention was feasible, but only given inpatient, so it is unclear if it is feasible for an outpatient population and these regimens are currently most typically administered outpatient in the United States. Although promising, it would need to be repeated to be generalizable.
Nurses should take away from this study that there is the possibility that endurance, strength, and QOL are improved by a program of strength and endurance training during chemotherapy. The results are not generalizable and would need further studies to confirm. There was no harm, but it cannot be recommended based solely on this study at this time.
Maeda, T., & Hayakawa, T. (2017). Dyspnea-alleviating and survival-prolonging effects of corticosteroids in patients with terminal cancer. Progress in Palliative Care, 25, 117–120.
To evaluate the effectiveness of corticosteroid to improve dyspnea and prolong survival in patients with terminal cancer
Retrospective chart review of 52 patients with terminal cancer who received corticosteroid for dyspnea. Effectiveness of corticosteroid to reduce dyspnea was assessed using the Support Team Assessment Schedule (STAS-J) and patients were classified as responders (n = 30) and non-responders (n = 22) based on STAS-J scores. Survival was compared between the groups, with patient survival being the primary endpoint.
Retrospective chart review of terminal patients who received either oral or IV corticosteroids. Patients were classified as responders or non-responders and survival was compared between the groups.
Effectiveness of corticosteroids to alleviate dyspnea was assessed using the Support Team Assessment Schedule (STAS-J) dividing patients into responders and non-responders. The Mann-Whitney U test compared survival between responders and non-responders, the chi-square test analyzed patient background information, and the Common Terminology Criteria for Adverse Events (CTCAE), version 4, evaluated adverse effects.
There was significant improvement in survival for patients who responded to corticosteroids with reduced dyspnea then those that did not using the Mann-Whitney U test (8.5 versus 5 days, p = 0.0019). Side effects observed with corticosteroids included insomnia (15.4%), delirium (11.5%), and hyperglycemia (3.8%).
The use of corticosteroid alone or in combination with opioid did reduce dyspnea in some patients at end of life and, therefore, resulted in prolonged survival. However, side effects of corticosteroids must be taken into consideration when assessing reduced dyspnea and evaluating the benefit of prolonged survival.
Dyspnea occurs at end of life and can be difficult to manage. Therapies to effectively reduce dyspnea at end of life are needed. Corticosteroid therapy may alleviate dyspnea in some patients at end of life. Nurses must continue to assess effectiveness of corticosteroids to reduce dyspnea along with side effects that may occur from therapy.
Starlight therapy consists of a moving low-light image of green stars against a dark blue background with moving clouds projected via a laser light lamp on the ceiling in the patient’s room.
Liu, F., Du, Y., Cai, B., Yan, M., Yang, W., & Wang, Q. (2017). A clinical study of polyethylene glycol recombinant human granulocyte colony-stimulating factor prevention neutropenia syndrome in patients with esophageal carcinoma and lung cancer after concurrent chemoradiotherapy. Journal of Cancer Research and Therapeutics, 13, 790–795.
To compare the efficacy and safety of PEG-rhG-CSF (prevention cohort) and rhG-CSF (delayed therapy cohort) for febrile neutropenia and, therefore, hospitalization of concurrent chemoradiation treatment of esophageal carcinoma and patients with lung cancer
Prophylactic application: G-CSF administered 24 hours after chemotherapy completion, 100 μg/mg PEG-rhG-CSF subcutaneously injected, whereas 150 μg of rhG-CSF was subcutaneously injected; the injection was performed once daily until leukocytes >10×109. Delayed application: G-CSF administered 5 days after the completion of chemotherapy.
Active treatment study for neutropenia-related hospitalizations for patients receiving concurrent chemoradiotherapy
SPSS, version 22.0, software (α = 0.05)
Comparison between the prevention group and the delayed group showed that the incidence of neutropenia-related hospitalizations were 4.44% and 14.62%, respectively (OR = 0.272, 95% CI [0.115, 0.642], p = 0.002). Comparison between the prevention group and the delayed group showed that the incidence of febrile neutropenia was 5.56% and 18.46%, respectively (OR = 0.26, 95% CI [0.12, 0.565], p = 0.001).
Prophylactic use of GCF decreased hospitalization rates and the use of IV antibiotics.
Nursing would teach effects of chemotherapy and depletion of white cells which could lead to hospitalizations and neutropenic fever. Administering this medication prophylactically would ensure less hospitalizations and less severe fevers as well as decrease use of antibiotics.
Blackwell, K., Gascon, P., Krendyukov, A., Gattu, S., Li, Y., & Harbeck, N. (2018). Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim: A phase III, randomised, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Annals of Oncology, 29, 244-249.
To confirm the safety and efficacy of the cost-effective filgrastim biosimilar EP2006 through a phase III, randomized, double blind study from the original PIONEER study, analyzing alternating treatments of EP2006 and reference filgrastim among patients receiving myelosuppressive chemotherapy. The alternating treatments were used to show there was no difference in efficacy, safety, or immunogenicity compared to patients who received EP2006 or filgrastim only.
Two patient groups from the original PIONEER study in which patients were randomized into one of four arms in a 1:1:1:1 ratio was analyzed in this study. Patients received an initial dose of either EP2006 or filgrastim and then alternated treatments over six cycles of chemotherapy TAC regimen (docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2). The filgrastim was administered as 5 µg/kg body weight per day, subcutaneous injection from the second day of chemotherapy until reaching ANC ≥ 10 x 109/l following nadir or for a maximum of 14 days.
PHASE OF CARE: Active anti-tumor treatment
Randomized, double-blind, parallel-group, multicenter study of women (aged 18 years and older) with breast cancer receiving myelosuppressive chemotherapy
Multiple variables from the original dataset were measured including: FN (oral temperature 38.3 C and ANC < 0.5x109/l on the same day), incidence of infections, incidence of hospitalizations due to FN, time and depth of ANC nadir (the patient’s lowest ANC in the respective chemotherapy cycle), time to ANC recovery, and ANC profile. Adverse events were also evaluated across all cycles of chemotherapy and included patients who received one or more dose of study medication and had one or more post-baseline safety assessment and the switched safety population of all patients who received one or more dose of study medication after cycle 1. Immunogenicity was evaluated.
Comparing the switched groups (n = 109) to the filgrastim reference group (n = 52), there were three patients (3.4%) in the switched group who had febrile neutropenia across cycles 2-6 compared to no patients with FN in the reference group. Infections occurred in 9.3% of patients in the switched group and 9.9% in the reference group. There were no differences between groups for depth of ANC nadir, time of ANC nadir, and time course of ANC recovery. Treatment emergent adverse events were similar between groups with 42.1% in the switched group and 39.2% in the reference group. No neutralizing antibodies against recombinant human G-CSF were detected.
The biosimilar EP2006 is as safe and effective as filgrastim. There was no compromise in immunogenicity in EP2006, and EP2006 was shown to be equally clinically meaningful to filgrastim, but is more cost-effective.
Knowledge regarding risks for infections in women with breast cancer receiving TAC therapy and the utilization of EP2006 as an alternative to filgrastim for cost-effective improved outcomes.
Zhang, R., Chen, J., Huang, H., Ma, J., Meng, F., Tang, Y., . . . Han, M. (2017). Primary fungal prophylaxis in acute leukemia patients with different risk factors: retrospective analysis from the CAESAR study. International Journal of Hematology, 106, 221-228.
To identify subgroups of patients undergoing treatment for leukemia who would receive the most benefit from primary antifungal prophylaxis (PAP).
Retrospective subgroup analysis of the observational China Assessment of Antifungal Therapy in Hematological Disease (CAESAR) study. Invasive Fungal Disease (IFD) was defined per the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the NIH/NIAID Mycoses Study Group criteria and classified as possible, probable, and proven. Treatments were categorized as antifungal prophylaxis, empirical treatment, preemptive therapy, and treatment of established IFD.
Retrospective subgroup analysis of a large observational study.
Data analyzed from previously collected variables from patient medical records. Variables measured included demographic information, laboratory values (albumin [decreased y/n], chemotherapy, neutropenia status, renal dysfunction [y/n], indwelling central line [y/n], corticosteroid use [y/n], parenteral nutrition [y/n], primary antifungal prophylaxis (PAP) administered [y/n]). Type of antifungal medications were also analyzed.
Among the 2015 patients in this sub-study of patients with acute leukemia, 2,274 courses of chemotherapy were administered: 1,410 courses of chemotherapy for acute myeloid leukemia and 864 courses for acute lymphocytic leukemia. Patients treated for AML incurred more IFDs than patients with ALL (11.8% versus 7.1%, p < 0.001). IFD was also higher among patients who received induction chemotherapy (21.6%) compared to consolidation chemotherapy (3.7%) (p < 0.0001). IFD risk factors included decreased albumin, indwelling central line, parenteral nutrition, and being male. Receiving PAP was protective against IFD; significant for patients on induction chemotherapy (p < 0.0001).
PAP is effective against IFD in patients undergoing induction chemotherapy for acute leukemia. PAP may reduce the risk of IFD in patients receiving consolidation chemotherapy, having a decreased serum albumin, indwelling central line, receiving parenteral nutrition, or having severe neutropenia.
Risk of bias (no control group)
Understanding the risks for invasive fungal disease and recommending primary antifungal prophylaxis for patients receiving chemotherapy (particularly induction chemotherapy) for the treatment of acute leukemia.
Pana, Z.D., Kourti, M., Vikelouda, K., Vlahou, A., Katzilakis, N., Papageorgiou, M., . . . Roilides, E. (2018). Voriconazole antifungal prophylaxis in children with malignancies: A nationwide study. Journal of Pediatric Hematology/Oncology, 40, 22-26.
To determine the safety of voriconazole (VRC) as antifungal prophylaxis (AFP) in pediatric hematology/oncology patients.
Patients received IV VRC 5-7 mg/kg every 12 hours as AFP, not as empiric treatment. Dosing and duration of VRC therapy was at the discretion of the treating physician. Median VRC dose = 7 mg/kg. Median duration of VRC = 17 days (range = 1-31 days). Median number of AFP courses = 1.7 (range = 1-6) per patient.
Retrospective chart review
Researchers assessed the rate of breakthrough IFIs during AFP and tabulated the incidence, time of onset, and severity of all AEs related to VRC.
Only one breakthrough IFI was found in the 429 courses of VRC given to 249 unique patients. Median duration of AFP with VRC was 17 days (range = 1-31 days). Median number of courses of VRC was 1.7 (range = 1-6) per patient. Females required more courses of VRC (median = 2, range = 1-4) than males (median = 1, range = 1-6) (p > 0.05). The underlying malignancy had a significant effect on the number of courses of VRC, with patients with leukemia receiving a median of 2 courses (range = 1-6). Patients without leukemia required a median of one course (range = 1-4) (odds ratio = 0.47; 95% CI [0.047, 0.5]; p = 0.019).
Seventy AEs of any grade were reported (a rate of 16.3%). There was no significant correlation between age, sex, and type of AEs. Of the 70 AEs, 38.5% were grade I, 48.4% were grade II, and 12.8% were grade III. Severity of AEs was not impacted by sex (p = 0.745), age (p = 0.78), and type of AE (p = 0.365). None of the AEs was severe enough to warrant discontinuation of VRC.
VRC provides effective prophylaxis in pediatric hematology/oncology patients at risk for IFIs. AEs were tolerable and manageable. However, the pediatric population may not be able to report subjective AEs, which could result in underdiagnosis of AEs. The risk of long-term AEs remains unknown.
Risk of bias (no control group)
Although AFP with VRC is effective, safe, and fairly well-tolerated, nurses should monitor their patients for early signs of AEs.
Zapolskaya, T., Perreault, S., McManus, D., & Topal, J.E. (2018). Utility of fosfomycin as antibacterial prophylaxis in patients with hematologic malignancies. Supportive Care in Cancer, 26, 1979–1983.
To evaluate the incidence of breakthrough infections in patients with neutropenic hematologic malignancy unable to receive fluoroquinolone prophylaxis and receiving fosfomycin prophylaxis instead. Additional data collected to isolate offending organisms, types of infection, resistance patterns, and time from initiation of breakthrough infection to onset of fever.
Retrospective chart review
Descriptive statistics of collected data: median, range, frequencies, incidence rates, and percentages
New start of fosfomycin prophylaxis = 81% of patients; continuation of fosfomycin prophylaxis = 19%; rate of FN while on fosfomycin prophylaxis = 55% (in 23 admissions), median time to start of fosfomycin to fever onset = 10.5 days (range = 3-21 days); breakthrough infections = 19% (in 42 admissions); bacterial organisms isolated: # 5 Klebsiella spp, # 2 S. mitis/viridans, #1 Pseudomonas aeruginosa, #1 coagulase-negative Staphylococcus; types of breakthrough infections: # 7 bacteremia, # 1 cellulitis, # 1 urine, # 1 bacteremia plus cellulitis; # 5 history of an infection six months prior to fosfomycin propylaxis, two of which had breakthrough infection not related to prior infection; no infection-related deaths for those experiencing breakthrough infections.
In a retrospective chart review of 25 neutropenic hematologic malignancy patients considered high risk for infection and unable to receive standard quinolones prophylaxis, received fosfomycin prophylaxis. The percentage of breakthrough infections while on fosfomycin prophylaxis was only 19%.
This retrospective chart review provides limited evidence for low rate of breakthrough infections on fosfomycin prophylaxis in high-risk hematologic malignancy patients. For those patients unable to receive fluoroquinolones, comparative effectiveness of fosfomycin as an alternative to fluoroquinolones needs further study with large multi-site RCTs.
Hartman, S.J., Nelson, S.H., Myers, E., Natarajan, L., Sears, D.D., Palmer, B.W., . . . Patterson, R.E. (2018). Randomized controlled trial of increasing physical activity on objectively measured and self-reported cognitive functioning among breast cancer survivors: The memory and motion study. Cancer, 124, 192–202.
Examine the preliminary efficacy of a moderate-intensity aerobic exercise intervention, compared with a waitlist/attention control, on cognitive function among sedentary breast cancer survivors who reported cognitive problems.
The intervention included two groups: aerobic physical activity (targeting a goal of at least 150 minutes of moderate-to-vigorous physical activity over 12 weeks) versus waitlist/attention control (i.e., matching email contact frequency for intervention group with women’s health topics).
Participants randomly assigned to the aerobic physical activity group completed an in-person walking assessment, after which study staff used motivational interviewing to set physical activity targets to reach the target goal for the study. Participants were given a Fitbit, which was used by staff to provide feedback on increasing physical activity during calls at two and six weeks. Motivational emails were sent every three days.
Participants assigned to the control group received women’s health topic emails every three days.
Study assessments were done before and at the end of the intervention (i.e., approximately 12 weeks post-baseline).
PHASE OF CARE: Late effects and survivorship
Unblinded randomized controlled trial of moderate-to-vigorous physical activity versus waitlist/attention control with repeated measures
This pilot study provides evidence that moderate-to-vigorous physical activity shows preliminary efficacy to improve a specific domain of objectively-measured cognitive function, processing speed.
This study provides preliminary evidence that moderate-to-vigorous aerobic physical activity might improve the speed of doing mental tasks (i.e., processing speed), which is found to be impaired among some breast cancer survivors. The findings support future well-powered studies using aerobic physical activity to improve processing speed.
Gokal, K., Munir, F., Ahmed, S., Kancherla, K., & Wallis, D. (2018). Does walking protect against decline in cognitive functioning among breast cancer patients undergoing chemotherapy? Results from a small randomised controlled trial. PLOS ONE, 13, e0206874.
Assess the preliminary effectiveness of moderate-intensity walking, compared to usual care, on cognitive function during chemotherapy for non-metastatic, invasive breast cancer.
The intervention included two groups: moderate-intensity walking (targeting a self-managed goal of 150 minutes over 12 weeks) versus usual care.
Participants randomly assigned to the moderate-intensity walking group were given a booklet promoting reaching of the goal through self-management, starting with at least 10 minutes of walking and moving up to 30 minutes 5 days per week over 12 weeks. Participants were given a pedometer and were asked to record daily steps and complete the Borg Rating of Perceived Exertion Scale in a daily diary. Participants were also asked to log their weekly goals.
Participants assigned to the usual care group received no intervention.
Study assessments were done pre-chemotherapy (familiarization, no data collected); midway through chemotherapy (pre-randomization); and after chemotherapy (i.e., postintervention).
PHASE OF CARE: Active anti-tumor treatment
Unblinded randomized controlled trial of moderate-intensity walking versus usual care with pre-/post- assessments
This study provides evidence that a self-managed, home-based walking program of moderate-intensity is feasible during chemotherapy and may reduce declines in self-reported cognitive function during treatment.
This study provides preliminary evidence that self-managed, moderate-intensity walking might improve self-reported cognitive function, which is commonly reported to be impaired by breast cancer survivors. The findings support future well-powered studies evaluating walking to improve cognitive function.