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.
Myers, J.S., Mitchell, M., Krigel, S., Steinhoff, A., Boyce-White, A., Van Goethem, K., . . . Bender, C.M. (2019). Qigong intervention for breast cancer survivors with complaints of decreased cognitive function. Supportive Care in Cancer, 27, 1395–1403.
This purpose of the study is to evaluate the feasibility of conducting a three-arm single-blind RCT of an eight-week intervention to improve objectively and subjectively measured cognitive function in breast cancer survivors reporting cognitive complaints.
The study comprised three groups: (a) Qi-gong (Six Healing Sounds form: combination of diaphragmatic breathing, chanting of six healing sounds, and specific gentle arm movements), (b) gentle exercise (gentle arm movements and postures only), (c) attention control (survivorship-focused support group sessions facilitated by a clinical psychologist). Each group met for eight weekly 60-minute sessions. For both the Qi-gong and gentle exercise groups, participants were given instructions to complete 15-minute practice sessions, twice a day, and keep a log. Feasibility was defined by (a) achieving 45 evaluable patients (15 in each group); (b) 75% or greater adherence to weekly attendance for all groups and twice daily home practice for Qi-gong and gentle exercise; (c) 25% or less attrition. Patient-reported outcomes collected at baseline (T1), 8 weeks (T2), and 12 weeks (T3). Neuropsychological testing at T1 and T3 only.
PHASE OF CARE: Transition phase after active treatment
Single-blinded three arm randomized controlled trial (Qi-gong/Gentle Exercise/Attention Control)
Feasibility (primary aim): 36 evaluable patients at T3 (Qi-gong = 15, gentle exercise = 10, Attention control = 11). Adherence was 44%-67% for weekly sessions and 21%-31% for twice-daily home practice. 28% overall attrition rate.
Cognitive function (exploratory aim): Improvements in self-reported cognitive function, as measured by the FACT-Cog, were significantly greater in the Qi-gong group versus gentle exercise between T1 and T2 (perceived cognitive impairments subscale: p = 0.01, d = 1.14; perceived cognitive abilities subscale: p = 0.04, d = 0.75). No significant differences in self-reported cognitive function were noted between the groups from T2 and T3. Improvements on objectively measured processing speed (TMT-A) were significantly greater in the Qi-gong group versus gentle exercise between T1 and T3 (p = 0.07, d = 1.21). The attention control group improved more than the gentle exercise on the F-A-S test of verbal fluency between T1 and T3 (p = 0.02, d = 1.14).
Other: QOL improved for all three groups between T1 and T2. Distress significantly improved in the Qi-gong group compared to the support group (p = 0.05, d = 0.81) between T1 and T2. There was no significant improvement in fatigue or sleep disturbance scores.
This study provides support for the design of large studies to confirm the effectiveness of Qi-gong, which combines mindfulness-based elements with gentle exercise, for the improvement of perceived cognitive function and processing speed.
Interventions that combine mindfulness and gentle exercise, such as Qi-gong, may be feasible for some patients after chemotherapy for breast cancer and may have benefits in reducing cognitive complaints and improving speed in performing mental tasks. However, larger studies are needed to confirm these findings.
Cognitive training is any intervention aimed at improving, maintaining, or restoring mental function through the repeated and structured practice of tasks which pose an inherent problem or mental challenge (Sitzer, Twamley, & Jeste, 2006). Cognitive training can occur in different formats: group, individual, and computerized. Group cognitive training is provided to individuals in a group setting. Individual cognitive training is provided to patients in a one-on-one approach. Computerized cognitive training is the provision of such practice via a computer program.
Wu, L.M., Amidi, A., Tanenbaum, M.L., Winkel, G., Gordon, W.A., Hall, S.J., . . . Diefenbach, M.A. (2018). Computerized cognitive training in prostate cancer patients on androgen deprivation therapy: A pilot study. Supportive Care in Cancer, 26, 1917–1926.
The purpose of this pilot study is to examine the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training program compared to usual care in patients with breast cancer on androgen deprivation therapy (ADT).
BrainHQ, one hour per day, five days per week for eight weeks or 40 hours total
PHASE OF CARE: Late effects and survivorship
This was a two-group pilot study which randomized patients with prostate cancer who had been on ADT three months or longer to BrainHQ or usual care. Patents were screened and outcomes assessed at three time points: baseline (T1), immediately after 8 week intervention (T2), and 8 weeks later (T3). Participants were asked to complete 40 hours of training over 8 weeks.
87 of 174 (50%) were screened and consented. 73 completed baseline and 60 met randomization criteria. Retention was 72.5% for intervention and 100% in usual care at T2 and 72.5% and 100% in usual care at T3.
Overall, 50% randomized; however, less than 70% completed the study (10 hours or greater total of the intervention, results were greater than 70% if non-completers of the intervention were included. Participants were mostly satisfied with training (2.97, SD = 0.53 on scale of 1-4 with 4 being most positive). Most common barriers to training included difficulty finding time to train (n = 16, 52%), tiredness (39%), health problems (35%), boredom (32%), and distraction (16%). Preliminary efficacy of training was mixed: improvement noted in reaction time (p = 0.01); however, was unfavorable on verbal and visual memory. Memory was temporarily suppressed in the training group at T2 but normalized at T3. No effect of training noted on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life.
This study presented tentative support for the feasibility and acceptability of BrainHQ in prostate cancer patients. Preliminary efficacy of BrainHQ was mixed with improvement in reaction times but more research is needed to fully understand efficacy of cognitive training.
Cognitive training using BrainHQ may be feasible and mostly satisfying intervention for prostate cancer survivors. Additional studies are needed to determine efficacy.