Rajan, S.S., Lyman, G.H., Stearns, S.C., & Carpenter, W.R. (2011). Effect of primary prophylactic granulocyte-colony stimulating factor use on incidence of neutropenia hospitalizations for elderly early-stage breast cancer patients receiving chemotherapy. Medical Care, 49, 649–657.
The purpose of the study was to study the effect of administration of primary prophylactic (PPG) colony-stimulating factory and duration of administration on the occurrence of chemotherapy-induced neutropenia hospitalization in older adult patients with breast cancer.
The study sample included women older than age 66 years. Women with stage 0 were excluded because stage 0 does not require chemotherapy, and women with stage 4 were excluded because stage 4 palliative therapy is very different from standard first-course administration.
The SEER data from 16 registries (1994–2002) was used. The outcome of interest was neutropenia hospitalizations defined as ICD9 code 288.0X in the first, third or sixth months after the first course of chemotherapy. Administration of G-CSF had to be initiated within five days after the first course of chemotherapy as primary prophylaxis. G-CSF was defined according to procedures codes.
Inpatient
Observational study
Administration of PPG-CSF during the first course of chemotherapy reduced neutropenia hospitalizations by 16% with in first three months and 17% within the first six months of chemotherapy. Hospitalization rates within the first three months of chemotherapy initiation were three times higher in women receiving less than five days of PPG-CSF compared to women receiving PPG-CSF for five or more days. Hospitalization rates within the first one and six months were also lower with longer PPG-CSF.
PPG-CSF use is associated with reductions in patient healthcare utilization.
PPG-CSF received during the first three months, particularly after five days of initiation of the therapy, and to be taken for at least five days, would reduce the risk of neutropenia hospitalization among older adult patients with breast cancer.
Raison, C.L., Rutherford, R.E., Woolwine, B.J., Shuo, C., Schettler, P., Drake, D.F., . . . Miller, A.H. (2012). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: The role of baseline inflammatory biomarkers. Archives of General Psychiatry, 1–11.
To determine the effect of repeated intravenous injection of a monoclonal antibody, directed at the inflammatory cytokine tumor necrosis factor (TNF), on the mood of patients diagnosed with treatment-resistant depression (TRD); to note the effects of the intervention on the levels of inflammatory cytokines and high-sensitivity C-reactive protein (hs-CRP) and concentrations of TNF
Patients were randomized to receive either placebo or infliximab infusions of 5 mg/kg at baseline and at weeks 2 and 6. Assessments of clinical and inflammatory status (hs-CRP, TNF, and its soluble receptors I and II) were conducted at baseline and at weeks 1–4, 6, 8, 10, and 12.
Transition phase after active treatment
Randomized double-blind placebo-controlled trial
There were no differences in HAM-D score changes over time between groups. These scores declined significantly over time in both groups (p = 0.01). Subgroup analysis showed that, for patients with baseline hs-CRP concentration greater than 5 mg/L, those on infliximab had greater improvement in HAM-D scores (effect size = 0.41). Treatment response rates were not different between groups
Treatment with infliximab is not an effective intervention for treatment-resistant depression. However, as levels of hs-CRP increase, infliximab has greater effect. Antagonism of TNF is ineffective against treatment-resistant depression. More research is needed to determine inflammatory biomarkers in patients who may uniquely respond to immune-targeted therapies.
This study yields no results that can immediately be applied to practice. Nurse-researchers should consider constructing and implementing clinical trials aimed at exploring, developing, and understanding inflammatory biomarkers to identify immune-targeted therapeutic interventions.
Rahman, M.M., & Khan, M.A. (2009). Levofloxacin prophylaxis to prevent bacterial infection in chemotherapy-induced neutropenia in acute leukemia. Bangladesh Medical Research Council Bulletin, 35(3), 91–94.
The purpose of the study was to evaluate if prophylaxis with oral levofloxacin will reduce or delay the febrile neutropenic episodes in chemotherapy-induced neutropenia.
Patients enrolled were assigned randomly to receive 500 mg of levofloxacin orally once daily, or an identical-appearing placebo, starting on day 1 of chemotherapy. Prophylaxis was continued until neutropenia had resolved or fever was documented. Patients were examined daily for clinical signs of infection.
The primary end point of the study was the occurrence of fever, requiring empirical antibacterial therapy during neutropenia. Secondary end points were the type and number of documented infections, the use of parenteral antimicrobial agents during neutropenia, survival at the resolution of neutropenia, compliance, and tolerability.
Active treatment
Prospective, randomized, placebo-controlled, single-blinded study.
Levofloxacin prophylaxis reduced the incidence of fever (17/25 patients (68%) compared to18/23 patients (78%) in placebo group; relative risk = 0.87; absolute difference in risk = 10%, p < 0.001) and reduced the incidence of microbiological proven infection (4/25 [16%] in the levofloxacin group compared to 7/23 [30.4%] in the placebo group; relative risk = 0.52; absolute difference in risk = 14.4%; p < 0.001). However, patients in the levofloxacin group were more likely to have a fever that lasted more than seven days (23%) compared with the control group (12.5%, p not stated).
This prospective study does not make a strong case for the use of levofloxacin to prevent neutropenic fever in patients with acute leukemia..
This study suggests that levofloxacin may reduce fever and infection in patients with acute leukemia. There is a concern regarding antibiotic resistance with the use of prophylactic antibiotics.
Rahmani, S., & Talepasand, S. (2015). The effect of group mindfulness-based stress reduction program and conscious yoga on the fatigue severity and global and specific life quality in women with breast cancer. Medical Journal of the Islamic Republic of Iran, 29, 175.
To assess the effectiveness of a group mindfulness-based stress reduction program on fatigue severity and life quality measures in women with breast cancer
The intervention was a standard mindfulness-based stress reduction program consisting of mindfulness skills, meditation, relaxation, and yoga. The program was provided in a group setting once weekly over an eight-week period. Patients randomly were assigned to the intervention or control group, which received no intervention. Patients were excluded from the analysis if they did not want to continue to participate in the intervention or missed more than two sessions.
Randomized, controlled, trial
Role, emotional function, social function, and cognitive function improved over time in both groups. Pain and fatigue declined over time in both groups (p < 0.001). There was a significant effect of group assignment over time with greater improvements in the intervention group for fatigue and pain (p < 0.001) as well as multiple areas of functioning.
Mindfulness-based stress reduction may be helpful in the management of fatigue among women receiving treatment for breast cancer.
Mindfulness-based stress reduction may be helpful for patients with cancer in the management of fatigue and some aspects of quality of life. Additional research involving the use of therapy interventions provided in groups should include appropriate group and attention control conditions because these factors can be expected to have an effect on perceived symptom severity.
Raghavendra, R.M., Nagarathna, R., Nagendra, H.R., Gopinath, KS, Srinath, B.S., Ravi, B.D., … Nalini, R. (2007). Effects of an integrated yoga programme on chemotherapy-induced nausea and emesis in breast cancer patients. European Journal of Cancer Care, 16, 462-474.
To examine the effects of an integrated yoga program in reducing frequency and intensity of nausea and vomiting in chemotherapy-naïve patients with early stage breast cancer
Patients were randomly assigned to receive either a yoga intervention or a supportive therapy intervention. Patients in the yoga group received both supervised and home practice of yoga sessions for 60 minutes daily, starting prior to chemotherapy. These patients received supervised initial training, audio and videocassettes for home use, and a supervised home visit. Patients in the control group received supportive therapy and coping preparation during hospital visits over a complete course of chemotherapy. Both interventions were initiated prior to the first chemotherapy cycle. The yoga instructor was trained in counseling and facilitated both groups.
Patients were recruited from a comprehensive cancer care center in India.
Patients maintained diaries to record episodes of vomiting and duration of nausea, and, at the fourth cycle, they completed the Morrow Assessment of Nausea and Emesis (MANE), State-Trait Anxiety Index (STAI), Beck Depression Inventory (BDI), Functional Living Index-Cancer (FLIC), and a symptom checklist questionnaire.
The yoga intervention was effective in reducing the frequency and intensity of nausea and the intensity of anticipatory nausea and vomiting in women with early stage breast cancer.
Raftopoulos, H., Boccia, R., Cooper, W., O'Boyle, E., & Gralla, R.J. (2015). Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: Analysis by American Society of Clinical Oncology emetogenicity criteria. Future Oncology, 11, 2541–2551.
To examine whether the post hoc analysis presented here confirms the original findings of the APF530 phase III trial, that APF530 is an alternative to palonsetron for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC)
In the original study, patients were randomized 1:1:1 to receive APF530 500 mg subcutanous plus placebo IV, APR530 250 mg subcutaneous and palonosetron 0.25 mg plus placebo. The first objective was to establish noninferiority of APF530. For the second cycle, the placebos were dropped, and individuals who had been randomized to the palonsetron were randomly assigned to either 250 or 500 mg of APR530.
ACUTE PHASE OF CARE: Active antitumor treatment
Secondary analysis of a randomized, controlled study
Complete response (CR) was measured by no emetic episodes and no use of rescue medications during the acute and delayed phases of CINV after cycle one. Noninferiority was established if the confidence interval for the difference in CR was greater than 15%.
The results of this secondary analysis did not find significance difference between APF530 and palonsetron for acute and delayed CINV in patients receiving HEC and MEC regimens. There were no notable differences in the results of this study and the original analysis, except they found numerically higher CR rates in patients receiving MEC and lower CR rates in patients receiving HEC for all study arms.
The post hoc analysis presented here confirms the original findings of the APF530 phase III trial, that APF530 is an alternative to palonsetron for preventing acute and delayed CINV after MEC and HEC.
Post hoc analysis
The results of this study will not change the current use of slow-release granisetron (noninferior to palonsetron) for acute and delayed CINV after HEC and MEC, but confirms previous knowledge with new ASCO emetogenicity criteria.
Raftopoulos, H., Cooper, W., O'Boyle, E., Gabrail, N., Boccia, R., & Gralla, R.J. (2015). Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: Results of a prospective, randomized, double-blind, noninferiority phase 3 trial. Supportive Care in Cancer, 23, 723–732.
To compare two dose levels of AFP530 and palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)
Eligible patients were 18 years of age or older with a confirmed malignancy scheduled to receive single-day MEC or HEC defined by the Hesketh algorithm. Patients were stratified according to their chemotherapy emetogenicity (MEC or HEC) and randomized 1:1:1 to receive APF530 at 250 mg subcutaneously (granisetron 5 mg) plus a placebo IV; APF530 at 500 mg subcutaneously (granisetron 10 mg) plus a placebo IV; or palonosetron IV at 0.25 mg plus a placebo subcutaneously prior to chemotherapy. After cycle 1, all patients were invited to continue in the study. If they consented, they were rerandomized to maintain blinding, but only patients who received IV palonosetron in cycle 1 were actually randomized 1:1 to receive APF530 at 250 or 500 mg subcutaneously for less than or equal to three subsequent cycles. Efficacy measures were determined from patient diaries in which patients recorded emetic episodes, rescue medications, and the severity of nausea for each 24-hour period after chemotherapy.
Prospective, multicenter, randomized, double-blinded, double-dummy, parallel-group, phase 3 trial
The original analysis under the Hesketh criteria for emetogenicity demonstrated that AFP530 at 250 and 500 mg subcutaneously was noninferior to palonosetron as assessed by complete response (CR) in the control of acute CINV after MEC (CR rates of 74.8% and 76.9%, respectively, versus 75% for palonosetron). The result was similar for patients receiving HEC with acute CR rates of 77.7% and 81.3% for APF530 at 250 mg and 500 mg, respectively, versus 80.7% for palonosetron. APF530 at 500 mg subcutaneously also was noninferior to palonosetron in preventing delayed CINV after MEC with a CR rate of 58.5% versus 57.2% for palonosetron. The superiority of APF530 at 250 or 500 mg subcutaneously versus palonosetron at 0.25 mg IV in preventing delayed CINV after HEC in cycle 1 was not determined. However, CR rates were similar for APF530 at 500 mg subcutaneously and palonosetron at 0.25 mg IV. In a post hoc analysis, patients receiving chemotherapy regimens whose antiemetic risk had been revised according to the updated antiemetic practice guidelines (notably cyclophosphamide plus anthracyclines [reclassified from MEC to HEC] and carboplatin-based regimens [reclassified from HEC to MEC]) were reclassified at the request of the U.S. Food and Drug Administration. The results of this reanalysis showed no notable statistic or clinical difference in response rates between APF530 and palonosetron.
A single, subcutaneous APF530 injection offered a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC with similar safety profiles.
Single-dose APF530 subcutaneously was noninferior to palonosetron at 0.25 mg IV for controlling acute CINV in patients who received single-day MEC or HEC as determined by CR. This provides another option for antiemetic chemotherapy premedication. Because of changing emetic classifications, antiemetic study interpretation can be a complicated process. The findings of this study cannot be generalized to multiday chemotherapeutic regimens because multiday chemotherapeutic regimens were not included in the design of the study.
Raeessi, M.A., Raeessi, N., Panahi, Y., Gharaie, H., Davoudi, S.M., Saadat, A., . . . Jalalian, H. (2014). \"Coffee plus Honey\" versus \"topical steroid\" in the treatment of chemotherapy-induced oral mucositis: A randomised controlled trial. BMC Complementary and Alternative Medicine, 14, 293-6882-14-293.
To draw a comparison between the therapeutic effects of treatment modalities (topical steroid, honey, honey plus coffee) in patients with oral mucositis
Patients were randomized to one of three groups that each received a 600 g syrup solution. The solution in the steroid group (S) contained 20, 8 mg Betamethasone solution ampoules. The solution in the honey plus coffee group (HC) contained 300 g of honey plus 20 g of instant coffee. The solution in the honey group (H) contained 300 g of honey. Every three hours for one week, patients were instructed to sip 10 ml of their solution and swallow it. Data were collected prior to the initiation of the intervention and one week later. Patients were not allowed to use any other anti-inflammatory agents during the study. Patients and providers were blinded to the groups.
Double-blinded, randomized clinical trial
All three regimens significantly reduced oral mucositis at the end of the intervention week (p < .05).
A steroid solution, honey plus coffee solution, or honey only solution reduced the severity of oral mucositis after one week of treatment.
Further investigation is needed on this intervention taking into account participants' diseases and chemotherapy regimens received.
Radbruch, L., Torres, L.M., Ellershaw, J.E., Gatti, A., Luis Lerzo, G., Revnic, J., & Taylor, D. (2012). Long-term tolerability, efficacy and acceptability of fentanyl pectin nasal spray for breakthrough cancer pain. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer, 20(3), 565–573.
To assess the long-term tolerability, acceptability, and consistency of fentanyl-pectin nasal spray (FPNS) in patients with breakthrough cancer pain
Newly enrolled patients participated in four study phases. Phase 1 was screening. Phase 2 consisted of dose titration based on the approach used in controlled trials: The lowest FPNS dose was uptitrated, one dose per episode of pain, to a maximum of 800 mcg per dose until two consecutive episodes of breakthrough cancer pain were successfully treated without causing adverse events. Phase 3 consisted of 16 weeks of open-label treatment: Patients were provided with a four-week supply of FPNS, either 100 mcg/spray or 400 mcg/spray, based on the findings in the titration phase. Patients self-administered FPNS. If FPNS was ineffective, patients could take their usual analgesia. Investigators initiated weekly calls to patients during the first four weeks. In these calls patients and investigators discussed progress, dose adjustments, and side effects. An investigator considered dose adjustment during the participant’s monthly visit. Consideration was based on information in an e-diary, which each patient submitted, and drug-related adverse events. Phase 4 was the end-of-treatment phase. Those previously enrolled in phase III CP043 (FPNS compared to placebo in the United States, Argentina, and Costa Rica) or CP044 (FPNS compared to immediate-release morphine sulphate in the European Union and India) went through phase 3 and phase 4.
Multicenter open-label study
Per patient reports, FPNS is generally easy to use and well tolerated for the treatment of breakthrough cancer pain. FPNS doses were relatively stable during this four-month study; typically, multiple dose changes were not required. Spray, as a means of delivery, is a benefit, especially to those who have difficulty taking pills. The FPNS had little effect on the nasal passages. The results of this study appear generalizable, and administration of fentanyl by means of a nasal spray appears to be acceptable in many institutions across the world. All these outcomes indicate that FPNS may be a helpful intervention for the treatment of breakthrough cancer pain.
Education regarding nasal spray administration seems to play a large role in the effectiveness of a spray-delivered intervention. Further research should investigate adverse events, to ensure the well-being of patients.
Radbruch, L., Sabatowski, R., Loick, G., Kulbe, C., Kasper, M., Grond, S., & Lehmann, K.A. (2000). Constipation and the use of laxatives: A comparison between transdermal fentanyl and oral morphine. Palliative Medicine, 14, 111–119.
To investigate constipation and the use of laxatives in patients with chronic cancer pain treated with oral morphine and transdermal fentanyl.
Patients were switched from long-acting morphine to fentanyl patches. Fentanyl doses were calculated with a conversion table based on a 100:1 dose ratio. If the calculated fentanyl dose was higher than 2.4 mg/day = 100 ug/hour (more than 270 mg/day slow-release morphine), more than one patch was used. Patients were treated with oral slow-release morphine for at least six days (morphine phase) until they reported stable pain intensity scores of 40 or less on a visual analog scale (0 = no pain, 100 = worst pain imaginable) for at least two days. Analgesic therapy then was switched from oral morphine to transdermal fentanyl (fentanyl phase). Fentanyl patches were changed regularly after three days. Fentanyl doses were increased when patients reported inadequate pain relief or had to take more than six rescue medications per day. The study was terminated after 30 days of transdermal therapy. Patients who completed the study until day 17 or longer were included in an intraindividual comparison of laxative intake using the Wilcoxon rank test.
This was an open, sequential, multi-center study.
The use of laxatives was reduced significantly with transdermal fentanyl.