Abdel-Rahman, O. (2016). Neurokinin-1 inhibitors in the prevention of nausea and vomiting from highly emetogenic chemotherapy: A network meta-analysis. Therapeutic Advances in Medical Oncology, 8, 396–406.
STUDY PURPOSE: To conduct a meta-analysis comparing the effectiveness of NK1 inhibitors in preventing chemotherapy-induced nausea and vomiting (CINV) attributed to highly emetogenic chemotherapy (HEC)
TYPE OF STUDY: Meta-analysis and systematic review
PHASE OF CARE: Active antitumor treatment
Antiemetic regimens including an NK1 inhibitor (aprepitant, fosaprepitant, rolapitant, casopitant, netupitant) prevent CINV attributed to HEC significantly more than antiemetic regimens that do not include it.
Antiemetic regimens containing an NK1 inhibitor prevent CINV attributed to HEC better than regimens that do not contain it.
Antiemetic regimens should include an NK1 inhibitor to maximally prevent CINV.
Abdel-Rahman, O., & Fouad, M. (2016). Rolapitant: A pooled analysis of its efficacy and safety in the prophylaxis of chemotherapy-induced nausea and vomiting. Future Oncology, 12, 871–879.
STUDY PURPOSE: To provide a detailed assessment of the efficacy and toxicity of regimens based on rolapitant in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV)
TYPE OF STUDY: Meta-analysis and systematic review
PHASE OF CARE: Active antitumor treatment
The pooled RR for the complete response (CR) was 1.23 (95% CI [1.18, 1.33], p < 0.00001) in the overall phase, 1.12 (95% CI [1.02, 1.24], p = 0.02) in the acute phase, and 1.19 (95% CI [1.13, 1.26], p < 0.00001) in the delayed phase. The pooled RR for no significant nausea in the overall phase was 1.17 (95% CI [1.04, 1.32], p = 0.008), and the pooled RR for no emesis in the overall phase was 1.24 (95% CI [1.18, 1.31], p < 0.00001). The efficacy analyses demonstated that rolapitant-based regimens are associated with higher rates of CR (both in overall, acute, and delayed phases). No significant nausea was present and no emesis was present compared with control regimens in highly and moderately emetogenic chemotherapy. The pooled RR of all grade constipation was 1 (95% CI [0.55, 1.82], p = 0.61), and the pooled RR of all grade headache was 1.05 (95% CI [0.57, 1.96], p = 0.87). Therefore, rolapitant-based regimens are not associated with an increased RR for constipation or headache compared with antiemetic control regimens.
This analysis demonstrated that rolapitant-based regimens are associated with higher rates of CR, no significant nausea, and no emesis compared with control regimens in highly and moderately emetogenic chemotherapy. In addition, no increased risk of toxicity with constipation or headache exists when compared with standard antiemetic control regimens. The authors concluded that rolapitant is a valid addition to other available standard antiemetic regimens for highly and moderately antiemetic chemotherapy.
Rolapitant is associated with higher CR rates, no significant nausea, and no emesis compared to other control regimens in highly and moderately emetogenic chemotherapy without increased toxicity. Rolapitant should be a recommended addition to control regimens that do not include a neurokinin inhibitor.
Abbas, S., & Seitz, M. (2009). Systematic review and meta-analysis of the used surgical techniques to reduce leg lymphedema following radical inguinal nodes dissection. Surgical Oncology, 20(2), 88–96.
To assess the efficacy of available strategies to reduce the risk and severity of leg lymphedema
Databases searched were MEDLINE (from January 1966 to April 2009), EMBASE (from January 1980 to April 2009), and the Cochrane Colorectal Cancer Group Specialized Register (January 2009).
Search keywords were inguinal node dissection, lymphedema, malignant melanoma, squamous cell carcinoma, saphenous vein, prevention, and combinations of these words.
Studies were included in the review if they
The authors did not list the exclusion criteria. However, in the results section, the authors mentioned that two studies were excluded from the meta-analysis because they did not focus on the effect of saphenous vein preservation.
Suitable studies were assessed using the Newcastle-Ottawa scale for evaluation of the quality of nonrandomized cohort studies. This scale uses a star system for evaluation of nonrandomized studies. The grading is based on three criteria: patient selection, comparability of study groups, and outcome assessment. The analysis included studies that scored 6 stars or higher and were considered suitable for inclusion in the meta-analysis. The total number of studies initially reviewed was 14. Of these, 12 were included in the report and 4 in the meta-analysis.
Meta-analysis was conducted with the studies that reported on saphenous vein preservation. The rest were individual reports and were not pooled. The primary outcome was the rates of leg lymphedema. Other outcomes, such as cellulitis, flap necrosis, lymphocele, the number of harvested nodes, and rate of cancer recurrence, were considered secondary endpoints. Studies deemed suitable according to the Newcastle-Ottawa scale were pooled, and the data was entered in ‘‘Metaview’’, which is used by the Cochrane methods for systematic reviews. All of the results were analyzed as dichotomous variables. Statistical heterogeneity in the results of the meta-analysis was assessed by graphical presentations of the confidence intervals (CI) on forest plots and by performing a χ2 test for heterogeneity, in which p = 0.1 was regarded as significant heterogeneity.
Data were analyzed using a random effect model and expressed in odds ratios and a Forest plot. Heterogeneity among the included studies was tested using the Cochrane Q test, with p values < 0.01 to ensure that odd ratios from separate studies were homogenously distributed. A funnel plot then was constructed to visually test for the presence of publication bias.
The search result defined few studies that reported results of saphenous vein sparing technique; some of those studies were found suitable for meta-analysis based on the Newcastle-Ottawa scale for nonrandomized studies. The meta-analysis showed significant reduction of lymphedema (odds ratio 0.24; 95% CI, 0.11–0.53) and other complications of inguinal node dissection. No randomized studies addressed this problem. Isolated studies reported on the benefits of other techniques, but none of them was suitable for meta-analysis.
Meta-analysis of the reported studies on sparing the long saphenous vein in inguinal node dissection suggests a reduced rate of lymphedema and other postoperative complications.
Other methods that may be beneficial are fascia preserving dissection, pedicledomental flap, and microsurgery. Sartorius transposition has not been shown to reduce the rate of complications. Randomized controlled trials are needed to prove the benefits of various technical modifications.
Aarts, M.J., Peters, F.P., Mandigers, C.M., Dercksen, M.W., Stouthard, J.M., Nortier, H.J., . . . Mattijssen, V. (2013). Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia. Journal of Clinical Oncology, 31, 4290–4296.
To evaluate whether neutropenia prophylaxis could be limited to the first two cycles of chemotherapy only, based on the observation that patient risk for febrile neutropenia (FN) is highest in the first two cycles
Patients receiving chemotherapy every three weeks with regimens associated with more than a 20% risk of FN were randomly assigned to receive a granulocyte–colony-stimulating factor (G-CSF) throughout all chemotherapy cycles (standard arm) or during the first two cycles only. Pegfilgrastim (6 mg) was given 24–30 hours after chemotherapy administration. Participating sites were stratified according to whether they used prophylactic antibiotics.
The incidence of FN was 10% with standard treatment and 36% in the experimental arm. Grade 3–4 neutropenia occurred in 6% of the standard arm versus 51% of the experimental arm, and confirmed infection occurred more often in the experimental arm. The study was closed prematurely because of an unacceptablely high rate of FN.
The findings showed that the incidence of FN was higher among patients who did not receive G-CSF during each cycle of chemotherapy.
The findings showed that patients who did not receive recommended CSF prophylaxis during each cycle of chemotherapy had significantly higher rates of FN. These results showed that the provision of prophylaxis according to recommended guidelines is important for FN prevention.
Aapro, M., Karthaus, M., Schwartzberg, L., Bondarenko, I., Sarosiek, T., Oprean, C., . . . Rugo, H. (2017). NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: Results of a randomized, double-blind, phase 3 trial versus oral palonosetron. Supportive Care in Cancer, 25, 1127–1135.
To compare the efficacy and safety of netupitant plus palonosetron (NEPA) compared to palonosetron alone in preventing chemotherapy-induced nausea and vomiting (CINV)
Chemotherapy-naïve patients receiving anthracycline- or cyclophosphamide-based chemotherapy were randomized to receive a single dose of PO NEPA (300 mg netupitant plus 0.50 mg palonosetron) and 12 mg dexamethasone or a single dose of 0.5 mg PO palonosetron and 20 mg dexamethasone on day 1, cycle 1, of their chemotherapy. Delayed (25-120 hours post chemotherapy) CINV was evaluated as the primary end point.
PHASE OF CARE: Active antitumor treatment
Double-blind, randomized
Participants who received NEPA and dexamethasone reported complete remission (no emesis or rescue antiemetics) significantly more than participants who received palonosetron and dexamethasone (p ≤ 0.001).
NEPA and dexamethasone may offer more control over CINV compared to palonosetron and dexamethasone.
Combination antiemetic therapies have been shown to provide more relief from CINV compared to single agents. The results of this study demonstrated that NEPA given with dexamethasone did prevent CINV better than palonosetron and dexamethasone.
Aapro, M., Fabi, A., Nole, F., Medici, M., Steger, G., Bachmann, C., … Roila, F. (2010). Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Annals of Oncology, 21, 1083–1088.
To compare two treatments (palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3) for the management of chemotherapy-induced nausea and vomiting (CINV) in the overall study period (days 1–5) and to show comparison between the two treatments in complete response (CR) rates
The study was conducted at multiple outpatient settings in Austria, Germany, Italy, and Spain.
This was a double-blind, randomized, controlled study.
Aapro, M., Bokemeyer, C., Ludwig, H., Gascon, P., Boccadoro, M., Denhaerynck, K., . . . Abraham, I. (2016). Chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim in elderly versus non-elderly cancer patients: Patterns, outcomes, and determinants (MONITOR-GCSF study). Journal of Geriatric Oncology. Advance online publication.
To determine if the granulocyte–colony-stimulating factor (G-CSF) biosimilar filgrastim had similar outcomes for adults and older adult patients actively undergoing treatment for cancer
This was a prospective observational study of patients prescribed biosimilar filgrastim in 140 centers in 12 European countries.
Prospective observational
Comparative analysis of various components outlined by the authors
No statistically significant differences existed in the rates of chemotherapy-induced neutropenia and febrile neutropenia episodes between either groups. G-CSF support is equally important in both groups. Older adult patients with underlying chronic conditions may be at higher risk for febrile neutropenia; in both groups, it is important to provide timely prophylaxis.
Timely G-CSF support is important in both older adult and adult patients receiving myelotoxic chemotherapy.
Nurses need to be aware of G-CSF administration for patients after chemotherapy. Independent of age group, it is important that patients receiving specific regimens get timely G-CSF treatment to prevent neutropenia duration.
Aapro, M.S., Bohlius, J., Cameron, D.A., Dal Lago, L., Donnelly, J.P., Kearney, N., . . . European Organisation for Research and Treatment of Cancer. (2011). 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. European Journal of Cancer, 47, 8–32.
The purpose of this article was to update existing guidelines for prophylactic granulocytye–colony-stimulating factor (G-CSF). The article focuses on patients receiving chemotherapy, not limited to one definition of febrile neutropenia (FN). No studies with pediatric patients or patients with leukemia were included.
This guideline resource used a process where articles were rated using the table listing below.
Level Type of Evidence
A Evidence of type I or consistent findings from multiple studies of types II, III, or IV
B Evidence of types Ii, II, or IV and findings are generally consistent
C Evidence of types Ii, II, or IV, but findings are inconsistent
D Little or no systematic empirical evidence
Information from papers included in meta-analyses were only used to answer questions not included in the meta-analyses. Publications available from Congress presentations previously included as abstracts were only used is they provided answers not yet presented. Authors were contacted if their abstracts were relevant and publications noted as missing or “in press” were included.
Regarding a search strategy, the MEDLINE, PreMEDLINE, EMBASE, and Cochrane Library databases were used.
Key words included antineoplastic agents, filgrastim, granulocyte–colony-stimulating factor, lenograstim, neoplasms, neutropenia, pegfilgrastim, and guideline
Articles were included if they were recent reviews, any primary papers deemed relevant, and meta-analyses subject to manual review. In addition to filgrastim and pegfilgrastim, two filgrastim biosimilar molicules, XMO2 and EP2006, daily G-CSFs have been approved in Europe.
Articles were excluded if their studies included patients younger than age 18 years or patients with a diagnosis of leukemia.
Recommendations Primary prophylactic G-CSF is recommended for patients at risk and should be started 24–72 hours following completion of the first cycle.
Step I:
Step 2:
Step 3:
Provides percent risk for development of FN for some tumor types based on chemotherapy regimen. Identifies additional risk factors, but provides little guidance on how to use these to calculate an increase in risk that would warrant prophylactic G-CSF.
The article included results from an updated literature search to identify patient and chemotherapy regimen risk factors for developing FN, use of prophylactic G-CSF, G-CSF with existing FN, impact of overall FN risk on G-CSF use, and choice of G-CSF formulation. It was difficult to identify new information as recommendations were combined with existing recommendations.
Aapro, M.S., Grunberg, S.M., Manikhas, G.M., Olivares, G., Suarez, T., Tjulandin, S.A. ... Macciocchi, A. (2006). A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Annals of Oncology, 17(9), 1441–1449.
To evaluate the safety and efficacy of palonosetron at two different doses (0.25 mg versus 0.75 mg) compared with a single dose of 32 mg ondansetron in preventing chemotherapy-induced nausea and vomiting (CINV) after highly-emetogenic chemotherapy
Patients were assigned to one of three treatment arms: palonosetron 0.25 mg, palonosetron 0.75 mg, and ondansetron 32 mg.
The study consisted of 673 patients, and final data were reported on 667 patients.
This was a phase III, multinational, randomized, double-blind, double-dummy, stratified, parallel-group, active-comparator trial.
Equal results were reported for palonosetron and ondansetron in the first 24 hours. In the delayed and overall phases, palonosetron (regardless of dose) was associated with higher complete response (CR) rates compared with ondansetron.
Aapro, M., Rugo, H., Rossi, G., Rizzi, G., Borroni, M.E., Bondarenko, I., ... Grunberg, S. (2014). A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Annals of Oncology, 25, 1328–1333.
To evaluate the safety and efficacy of NEPA (a combination of netupitant plus palonosetron) compared to palonosetron (PALO) alone
During cycle 1 of moderately emetogenic chemotherapy, patients received either a single dose of NEPA (a combination of 300 mg netupitant and 0.50 mg palonosetron) plus 12 mg dexamethasone, or a single dose of 0.50 mg palonosetron (PALO) plus 20 mg dexamethasone. Patients were randomized and stratified by region. Matching placebos were used for blinding in all groups. Metoclopramide tablets were provided for breakthrough, though treating physicians could select another medication. Data were collected daily on days 1–6 after chemotherapy (0–120 hours).
PHASE OF CARE: Active antitumor treatment
Phase 3 trial, multicenter, randomized, double-blind, double-dummy, parallel group design
A significant number of patients in the NEPA group achieved CR when compared to patients in the PALO group overall (p = 0.001), in the delayed phase of treatment (p = 0.001), and during the acute phase of treatment (p = 0.047).
NEPA, the combination of netupitant and palonosetron, was demonstrated to be safe and more effective than palonosetron alone in producing CR during the acute, delayed, and overall phases of treatment in patients receiving cycle 1 of moderately emetogenic therapy.
Chemotherapy-induced nausea and vomiting (CINV) guidelines recommend antiemetic therapies targeting multiple pathways involved in emesis. NEPA, the novel combination of netupitant and palonosetron, uses an NK1 receptor antagonist and a 5-HT3 receptor antagonist to maximize CINV control. NEPA was shown to be more effective than palonosetron alone in producing CR during the acute, delayed, and overall phases of cycle 1 of moderately emetogenic therapy. The majority of this sample, however, were women diagnosed with breast cancer. The findings may not be generalizable to males or to other types of cancer.