Weycker, D., Li, X., Barron, R., Li, Y., Reiner, M., Kartashov, A., . . . Garcia, J. (2016). Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice. Supportive Care in Cancer, 24, 2481–2490.
To investigate the receipt of colony-stimulating factor (CSF) prophylaxis and associated risks of febrile neutropenia (FN)
Data from two large U.S. claims repositories from 2006–2014 were obtained for analysis. Data included patients aged older than 18 years who received at least two cycles of myelosuppressive chemotherapy. The analysis was focused on the use of pegfilgrastim; patients who received other CSFs were excluded from the analysis. Patients who received and did not receive pegfilgrastim prophylaxis were matched according to variables in multivariate regression, including the being at intermediate/high risk for neutropenia and cancer type.
FN episodes were identified based on hospital admission with a diagnosis of neutropenia, fever, or infection. FN episodes requiring outpatient care, including emergency department visits, were defined as Healthcare Common Procedure Coding System (HCPCS) code for IV antimicrobial therapy on the same date as a diagnosis of neutropenia, fever, or infection.
Of the patients, 5.3% were not given second-cycle pegfilgrastim prophylaxis. Second-cycle FN among comparison patients was 3.8% versus 2.2% among those who received propylaxis (95% confidence interval [CI] [1.2, 2.5], p = 0.002). With a narrower definition of FN, 3.5% without prophylaxis had FN compared to 0.8% in the group that received second-cycle pegfilgrastim (odds ratio [OR] = 3.5, p < 0.001).
The findings suggest that the odds of developing FN in the second cycle of chemotherapy are higher among patients who discontinue CSF prophylaxis compared to those who continue prophylaxis.
Some evidence suggest that ongoing CSF prophylaxis is not consistently provided in at-risk patients. This study, although it had some limitations, suggests that the discontinuation of prophylaxis along the course of treatment with myelosuppressive chemotherapy for patients at an intermediate or high risk for FN is associated with an increased incidence of FN.
Weycker, D., Barron, R., Edelsberg, J., Kartashov, A., Legg, J., & Glass, A.G. (2014). Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: The importance of duration of prophylaxis. BMC Health Services Research, 14, 189-6963-14-189.
To determine if the duration of filgrastim prophylaxis affects the risk of chemotherapy-induced neutropenic complications (CINC), healthcare costs, and mortality
This is a retrospective study of medicals claims from two large healthcare claims databases, the Thomson Reuters MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Database (MarketScan Database, 2001–2010) and the Intercontinental Marketing Services LifeLink Database (LifeLink Database, 2001–2008). Claims for chemotherapy, filgrastim, and hospital admissions were analyzed to determine the number of daily filgrastim doses following a chemotherapy cycle and neutropenic complications.
Retrospective study of medical claims
If patients were treated with one to three days of filgrastim prophylaxis, the risk of CINC during a cycle of chemotherapy was 2.9%. If they were treated with four to six days of filgrastim prophylaxis, the risk of CINC was 2.7%. If the patient was treated with seven or more days, the risk of CINC was 1.8%. In adjusted analyses, the odds of CINC were 2.4 (95% = CI, 1.6–3.4) higher with one to three days of filgrastim prophylaxis versus seven or more days and 1.9 (1.3–2.8) times higher with four to six days of filgrastim prophylaxis versus seven or more days. In the pivotal trials of filgrastim prophylaxis, 10–11 days of filgrastim prophylaxis were needed for adequate neutrophil recovery, yet this study demonstrated that in actual practice, 95% of patients received fewer than 10 days of filgrastim prophylaxis and 58% received only one to three days. In a subgroup of 358 patients who developed CINC and the healthcare expenditures were available, CINC-related healthcare expenditures were $18,912 (14,570– 23,581) with one to three days of prophylaxis (n = 225), $14,907 (11,155–19,728) with four to six days (n = 94), and $13,165 (9,595–17,144) with seven or more days (n = 39). In a subgroup of 228 patients for whom discharge status was available, in-hospital mortality was 8.4% (4.6–14.8) with one to three days of prophylaxis (n = 119), 4% (1.4–11.1) with four to six days (n = 75), and 0% (0–10.2) with seven or more days (n = 34).
Administration of less than seven days of daily filgrastim was not as effective as seven or more days of daily filgrastim to prevent chemotherapy-induced neutropenic complications. The use of seven or more days of filgrastim as primary prophylaxis to prevent chemotherapy-induced neutropenic complications also decreased healthcare costs and mortality.
In clinical trials evaluating the efficacy of CSF prophylaxis, patients were treated with 10 or more daily doses of filgrastim. However, in actual practice, the majority of patients receive prophylaxis with fewer than 10 doses of daily filgrastim, which increases the risk of chemotherapy-induced neutropenic complications, mortality, and healthcare costs. Clinicians need to be aware of most effective CSF dosing requirements.
Weycker, D., Malin, J., Barron, R., Edelsberg, J., Kartashov, A., & Oster, G. (2012). Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim as prophylaxis against hospitalization for neutropenic complications in patients with cancer receiving chemotherapy. American Journal of Clinical Oncology, 35, 267–274.
The purpose of this study was to assess differences in risk of hospitalization for neutropenic complications among patients with solid tumors who received prophylactic filgrastim, pegfilgrastim, or sargramostim during their first observed course of chemotherapy from July 2001 to June 2007.
Prophylactic administration of filgrastim, pegfiltrastim, or sargramostim
Retrospective cohort study
Statistical analyses included using medical claims information from two large databases (Thomson Reuters MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Database), calculation of duration in days of use of each CSF, independent samples t test for continuous factors and chi-square for multilevel categorical factors. Generalized estimating equations were used to assess risk of hospitalizations.
Risk of hospitalization for neutropenia was 2.1% (filgrastim prophylaxis, n = 8,286), 1.1% (pegfilgrastim prophylaxis, n = 67,247), and 2.5% (sargramostim prophylaxis, n = 1,736) and, for nuetropenia, fever, or infection for prophylactic use of filgratim, pegfilgratim, and sargramostim was 4%, 2.6%, and 2.5%, respectively. Risk of hospitalizations for all causes was 7.9%, 5.3%, and 9.6%, respectively. Adjustments were made in the statistical analysis for patient characteristics, type of cancer, and chemotherapy regimen.
Prophylactic pegfilgrastim administration is associated with less risk of hospitalizations for neutropenia/neutropenic-related complications than either prophylactic filgrastim or sargramostim in patients undergoing chemotherapy treatments for a variety of cancers.
Recommendation of the use of prophylactic pegfilgratim may be warranted. Patient education regarding neutropenia, neutropenic-related complications, and side effects of pegfilgratim is essential. Nurse-led discussions of using pegfilgratim instead of filgratim or sargramostim with the oncology healthcare team could ensue.
Weycker, D., Li, X., Figueredo, J., Barron, R., Tzivelekis, S., & Hagiwara, M. (2016). Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: Does timing of administration matter? Supportive Care in Cancer, 24, 2309–2316.
To evaluate the timing of pegfilgrastim administration
Data from two large claim systems repositories obtained from 2003 to 2011 were pooled for analysis. Patients included were adults receiving at least one course of chemotherapy for a solid tumor or non-Hodgkin lymphoma. Patients were identified as receiving intermediate or high-risk regimens, and pegfilgrastim use was determined using Healthcare Common Procedure Coding System (HCPCS) codes on claims with service dates up to three days after the last chemotherapy administration of a cycle. Patients were grouped based on whether pegfilgrastim was given on the same day as the last chemotherapy dose or on days 2–4 after chemotherapy. Chemotherapy cycles that used different colony-stimulating factors (CSFs) were excluded from the analysis. The analysis was done for all cases in the first cycle and for all febrile neutropenia (FN) episodes.
The study was shown to be sufficiently powered. Overall, FN occurred in 3.9% of those receiving same-day prophylaxis in the first cycle compared to 2.8% of those receiving pegfilgrastim on days 2–4 after chemotherapy (p < 0.001). Across all cycles, FN occurred in 2.5% of the same-day patients versus 1.9% of the prophylaxis patients on days 2–4 (p < 0.001). Overall, pegfilgrastim was given on the same day as the last chemotherapy dose in 12% of the cases.
The findings suggest that the timing of pegfilgrastim administration does matter, and that administration according to prescribing information is more effective than administration on the last day of the chemotherapy cycle.
The findings suggest that the administration of pegfilgrastim according to the timing outlined in prescription information is more effective than administration on the last day of the chemotherapy cycle. While an additional patient visit for this injection may not be convenient, it is worth the reduction in risk for FN and attendant infectious complications. The findings point to the need for the development of practical alternatives to facilitate adherence to essential schedules, such as simple devices for patients to self-administer CSFs as needed, as is done with medications like insulin.
Wevers, M.R., Ausems, M.G., Verhoef, S., Bleiker, E.M., Hahn, D.E., Brouwer, T., . . . Aaronson, N.K. (2015). Does rapid genetic counseling and testing in newly diagnosed breast cancer patients cause additional psychosocial distress? Results from a randomized clinical trial. Genetics in Medicine, 18, 137–144.
To assess the psychosocial impact of rapid genetic testing and counseling among women with newly diagnosed breast cancer
Patients were randomly assigned to rapid genetic counseling and testing (RGTC) or usual care control groups. Those in the RGTC group were offered an appointment with a clinical geneticist within five working days, and rapid DNA testing with results were provided within about four weeks. Participants complete study measures at baseline, and at 6- and 12-month follow-ups.
PHASE OF CARE: Diagnostic
Ninety-six percent of those in the experimental group had genetic counseling consultation, and 33% had DNA testing prior to surgery. In the usual care group, 71% had genetic counseling and 62% had DNA testing, 10% prior to surgery. There were no differences between groups in worries, anxiety, depression, quality of life (QOL), decisional conflict, or satisfaction with decision-making. In both groups, worries and measures of psychosocial distress declined over time.
Findings did not show that offering rapid genetic counseling and testing had any effect on QOL, anxiety, or depression among individuals newly diagnosed with breast cancer.
Westbury, C., Hines, F., Hawkes, E., Ashley, S., & Brada, M. (2000). Advice on hair and scalp care during cranial radiotherapy: A prospective randomized trial. Radiotherapy and Oncology, 54, 109–116.
To establish whether standard scalp care, as usually practiced by the patient, affects severity and course of acute skin radiation side effects, and to what extent advice on changing normal routine of hygiene causes distress
Patients receiving cranial radiation therapy were randomized to two groups. Group 1 patients were advised to continue normal scalp care. Group 2 patients were advised to avoid washing the irradiated area. Hair washing was not prohibited, but patients were advised to avoid it. Patients were assessed weekly over 10 weeks from the start of treatment, with recording of symptoms by patients and clinical assessment by an observer.
The study took place at The Royal Marsden NHS Trust in London, England.
The study used a randomized controlled trial design.
No differences were reported between scores of skin reaction in the two groups. Itching was the main local symptom experienced by both groups, with no significant differences. A marginal difference occurred between patient groups at six weeks, with the patients in group 2 having more severe symptoms.
The practice of normal hair washing is not associated with increased severity of adverse skin reaction caused by megavoltage cranial radiation therapy. The time course of skin reaction was also not affected by the different practice of hair washing. Mild-to-moderate skin reaction is not exacerbated in patients continuing their usually regimen of hair care.
Wenzell, C.M., Berger, M.J., Blazer, M.A., Crawford, B.S., Griffith, N.L., Wesolowski, R., . . . Layman, R.M. (2013). Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy. Supportive Care in Cancer, 21, 2845–2851.
To compare the effect of single-day ondansetron use versus palonosetron in combination with aprepitant and dexamethasone
Patients were stratified into cisplatin and noncisplatin chemotherapy groups and then randomized. On day 1 prior to highly emetogenic chemotherapy (HEC), patients in group 1 received palonosetron at 0.25 mg IV. Group 2 received ondansetron at 24 mg orally 30 minutes before chemotherapy. Both groups received oral aprepitant at 125 mg on day 1 (60 minutes prior to chemotherapy) then 80 mg on days 2 and 3, and oral dexamethasone at 12 mg on day 1 then 8 mg on days 2, 3, and 4. Data were recorded on days 1–6 following chemotherapy administration.
Prospective, open-label, randomized pilot study
Thirteen patients (65%) in the palonosetron arm and eight patients (40%) in the ondansetron arm achieved an overall complete response (CR). In the acute setting, 11 patients (55%) in the ondansetron group and 15 (75%) in the palonosetron group achieved a CR. In the delayed setting, nine patients (45%) in the ondansetron group and 13 (65%) in the palonosetron group achieved a CR. In the ondansetron group, 11 patients reported the use of rescue antiemetics, and in the palonosetron group, seven patients reported antiemetic use (in both acute and delayed time periods). Few patients experienced episodes of retching or vomiting. Seven patients in the ondansetron group and eight in the palonosetron group reported acute nausea. Delayed nausea was reported by 11 patients in the ondansetron group and 12 in palonosetron group.
This pilot study demonstrated a consistently higher rates of CR and lower rates of vomiting and retching in the palonosetron group although there was no statistically significant difference.
Take caution before interpreting the results of this study because it did not use the most robust research design (i.e., randomization, blinding, placebo-control) to detect the drug's efficacy. This study highlighted the need to conduct a large, adequately powered study.
Wenzel, J. A., Griffith, K. A., Shang, J., Thompson, C. B., Hedlin, H., Stewart, K. J., . . . Mock, V. (2013). Impact of a home-based walking intervention on outcomes of sleep quality, emotional distress, and fatigue in patients undergoing treatment for solid tumors. The Oncologist, 18, 476-484.
To evaluate the impact of a home-based walking program on patient symptoms of fatigue, sleep disturbances, and mood.
Patients were randomly assigned to the walking program or a usual care control group. The exercise intervention included a walking prescription based on the American College of Sports Medicine guidelines. The targeted exercise prescription included a brisk 20- to 30-minute walk with five-minute warm-ups and cool-downs five days per week. Exercise participants wore pedometers. Usual care patients wore pedometers during the first two weeks only. Throughout the study, patients in both groups received telephone contact on a biweekly basis to discuss physical activity and any concerns. For those in the exercise program, adjustments to the program were made, barriers to walking were discussed, and strategies for resolution were planned.
Patients were undergoing the active antitumor treatment phase of care.
This was a randomized, controlled trial.
Analysis of dropouts showed that significantly more ethnic minorities and those with lower educational levels withdrew (p < 0.03). There were no differences at the end of the study in sleep quality. There were no differences between groups in overall mean emotional distress scores; however, dose-response analysis showed that those who exercised more had less emotional distress (p = 0.03). There were no between-group differences in fatigue; however, analysis showed that those who exercised more had lower fatigue scores (p = 0.03). Subgroup analysis among patients with prostate cancer showed that exercise group members had better sleep quality (p < 0.001), less emotional distress (p = 0.048), and less fatigue (p = 0.009). PAQ findings were moderately correlated with pedometer results, suggesting that the PAQ may be a reasonable measure of exercise dose (Spearman = 0.37; p = 0.002).
Findings suggested that a home-based exercise program can be beneficial in patients receiving cancer treatment to reduce fatigue. Among patients with prostate cancer, the program resulted in improved sleep quality and less emotional distress and fatigue.
A home-based walking program is a simple intervention that can be beneficial to patients, and study findings showed that patients who exercised more had less fatigue and improved mood. In patients other than patients with prostate cancer, it did not appear that exercise improved sleep quality. This study included biweekly telephone follow-ups. Other studies have not shown the same level of results with home-based walking, suggesting that the follow-up component is probably important to maintain patient exercise program use. Of interest, patients who were less educated and of ethnic minorities were more likely to drop out of the study. This suggests that these groups of patients need to be examined more in order to see what interventions will be most likely to appeal to them.
Wenzel, L., Osann, K., Hsieh, S., Tucker, J.A., Monk, B.J., & Nelson, E.L. (2015). Psychosocial telephone counseling for survivors of cervical cancer: Results of a randomized biobehavioral trial. Journal of Clinical Oncology, 33, 1171–1179.
To study the effects of psychosocial telephone counseling on anxiety, quality-of-life domains, and biomarkers
Eligible patients were randomly assigned to the telephonic intervention or usual care. Those receiving the intervention received a five-minute pre-call to reintroduce the purpose of the intervention and schedule initial sessions. Patients received four sessions of 20-60 minutes for education and counseling for problem solving, social support, communication skill development, and problem identification based on the transactional model of stress and coping. Follow-up letters with session summary and suggested homework assignments were mailed after each session. Surveys were mailed to participants for completion at baseline, 4 months, and 9 months.
Randomized, controlled trial
Patients assigned to the intervention had significantly better scores for depression (p = 0.041) and cancer-specific concerns at four months (p < 0.05). There was no difference between groups in anxiety at four months. Patients assigned to the intervention demonstrated continued improvement in gynecologic problems at nine months. At nine months, there was no difference between groups in depression or anxiety.
Longitudinal evaluation of a telephonic psychoeducational intervention among survivors of cervical cancer showed benefit for depression and gynecologic problems in the first four months after the intervention. These differences were not maintained over the longer term.
Telephone-delivered psychoeducational intervention was associated with reduced depression and cancer concerns within the first few months of the intervention; however, these benefits did not appear to be maintained over the longer term. It is possible that there is a need for continued intervention in order to benefit patients in the longer term. Findings suggest that a telephone intervention delivery can be effective, and may be a practical way to be able to deliver this type of intervention, particularly for patients in rural areas, or those otherwise unable to travel to healthcare facilities.
Wenk, R., Bertolino, M., Ochoa, J., Cullen, C., Bertucelli, N., & Bruera, E. (2000). Laxative effects of fresh baker’s yeast. Journal of Pain and Symptom Management, 19, 163–164.
To determine whether the consumption of fresh baker’s yeast (FBY) reduces constipation in opioid-treated patients with advanced cancer.
FBY is a fungus most commonly used in the kitchen for raising dough. In Argentina, FBY is available in a paste form that can be mixed with liquids and meals. It is used as both a food supplement to provide vitamins, and a bowel regulator.
Patients initiated opioid therapy and concurrently received a daily dose of FBY in the morning for 15 days. FBY was dissolved in water at room temperature, with the option of mixing it with the patient’s favorite food. The initial dose was 6 g once a day in the morning. If patients did not have a bowel movement (BM), the dose was doubled daily until laxation occurred. The maximum dose was 50 mg. If no BM occurred within three days, a stimulant laxative was added to the treatment. If no BM occurred within an additional two days, an enema was ordered. Results were assessed daily by phone.
FBY was effective.
The cost of FBY as an intervention was low, at $2.50 per 15 days.