Boekhout, A. H., Vincent, A. D., Dalesio, O. B., van den Bosch, J., Foekema-Tons, J. H., Adriaansz, S., . . . Schellens, J. H. (2011). Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 29(29), 3862-3868.
Evaluate the efficacy of venlaxafine and clonidine for hot flashes in patients with breast cancer
Patients were randomly assigned to receive 75 mg venlafaxine, 0.1 mg clonidine, or placebo daily. Subjects were stratified by age, duration of hot flashes, concurrent endocrine therapy, and previous chemotherapy. Patients were treated for 12 weeks. Hot flash scores at week 12 were compared among the three groups.
N 80 AGE Median = 49, range 28-71
MALES (%) FEMALES (%)100%
KEY DISEASE CHARACTERISTICS 31% had age related symptoms, and 99% were post menopausal after breast cancer treatment. 52% received endocrine treatment
SITE Multi-site SETTING TYPE Outpatient LOCATION Netherlands
PHASE OF CARE Late effects and survivorship
Double blind placebo controlled RCT
Hot flash scores were lower in the clonidine group than the placebo group at week 12 ( p = .03), and lower in the venlaxafine group than placebo, though not statistically significant ( p = .07). Over the 12-week period, reduction in the venlaxafine group was 41% ( P<.001), 26% in the clonidine group ( p=.045), and 29% in the placebo group (p<.001). Those on venlaxafine tended to have some loss of appetite ( p = .003) as well as symptoms of nausea. Sleep and sexual function were not different between the two treatment groups. At week 12, anxiety and depression scores were higher in the venlafaxine than the clonidine group. (p = .03). Significantly lower hot flash scores began in the venlafaxine group compared to placebo in weeks 1-4 (p =.01), and in the clonidine group, lower scores began compared to placebo in weeks 5-8 ( p = .04)
Both venlafaxine and clonidine were slightly more effective than placebo in reducing hot flash symptoms in this group of patients. However, over the 12 weeks, all study groups showed significant reduction in symptoms.
Findings suggest that venlafaxine and clonidine may be of benefit in reducing hot flash symptoms in women with breast cancer. However, further research is needed for support, because placebo group also showed reduction in hot flashes. Some patients did have side effects from these medications; patients should be monitored for nausea, changes in appetite, anxiety, and depression if these medications are used.
Bodge, M., Shillingburg, A., Paul, S., & Biondo, L. (2014). Safety and efficacy of aprepitant for chemotherapy-induced nausea and vomiting in pediatric patients: A prospective, observational study. Pediatric Blood & Cancer, 61(6), 1111–1113.
To evaluate the effectiveness and safety of aprepitant related to the incidence and severity of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen for highly or moderately emetogenic chemotherapy in pediatric patients
Both male and female patients received a standard antiemetic regimen of ondansetron 0.45 mg/kg and dexamethasone 7 mg/2. In addition, they also received oral (solution or capsule) aprepitant with weight-based dosing based on the facility’s dosing table. Issues related to quality of life, such as severity of nausea, frequency of vomiting, appetite, and effect on activities of daily living (ADLs) were assessed using a survey. Since there are few studies using aprepitant in young patients weighing < 40 kg, the safety and tolerability of aprepitant in this population was the focus of this study.
Prospective, observational study
A patient survey was created by the investigators using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) grading system v4.0 and a 4-point Likert scale. It was completed at baseline, every day in which chemotherapy was administered, and for five days after the completion of chemotherapy. The survey evaluated the occurrence and severity of nausea, vomiting, appetite, and affect on ADLs during the phases of acute (0–24 hours), delayed (1–5 days), and overall phase (acute and delayed) after chemotherapy. The survey was administered by a study investigator or sent home with the patient’s caregiver. Complete response (CR) was defined as no nausea, vomiting, or no use of rescue drugs during the acute phase.
A total of 7 out of 16 (38.9%) CRs were achieved. No vomiting was reported in the overall (acute and delayed) phase in 16 out of 18 encounters (88.9%). In 5 out of 17 encounters (29.4%), no nausea was experienced in the overall phase. There was no interference in ADLs in 47.1% and no interference with appetite in 10 out of 18 (55.6%) patients. Rescue medications were not required in the acute phase for 7 out of 11 patients. There were no directly attributable adverse effects related to the systemic absorption of aprepitant, and it was found to be well-tolerated in this pediatric study population.
Oral aprepitant administration was found to be safe in patients as young as 12 months in moderate and highly emetogenic chemotherapy. During the study period, complete responses (no nausea, vomiting, or use of rescue drugs) were experienced in 33.3% of patients.
In the study population, weight-based dosing of oral aprepitant was well-tolerated and did not cause any systemic adverse reactions.
Bock, P.R., Hanisch, J., Matthes, H., & Zanker, K.S. (2014). Targeting inflammation in cancer-related-fatigue: A rationale for mistletoe therapy as supportive care in colorectal cancer patients. Inflammation and Allergy Drug Targets, 13, 105–111.
To examine fatigue levels in patients supported by a mistletoe preparation compared to patients who did not receive mistletoe
Data were extracted from the medical records of patients from the time of diagnosis or surgery (visit 1), during postoperative chemotherapy or chemoradiotherapy (visit 2), and at the end of postoperative therapy (visit 3). Patient complains related to fatigue and symptoms of inflammation were noted by the physician via interview. The results of patients allocated to mistletoe therapy were compared to those of the control patients. Mistletoe was provided as an injectable extract preparation that was given subcutaneously at a total average dose of 16–20 mg per week.
Retrospective, observational cohort study
Specific measurements were not described. Signs of inflammation and cancer-related fatigue were apparently coded by physicians as “yes” or “no” to indicate the presence of clinical signs.
There was a significantly increased odds ratio of suffering with fatigue among patients in the control group at visits 2 and 3 (p < 0.001). However, by visit 2, 85% of those in the mistletoe group had dropped out, and by visit 3, only 16 patients remained in the mistletoe group. The results regarding inflammation were not described.
This report provides insufficient evidence regarding the effects of mistletoe therapy on cancer-related fatigue.
This study does not provide any strong evidence regarding the efficacy of mistletoe extract for the management of cancer-related fatigue, and it does not provide evidence regarding the impact of this therapy on inflammatory markers. Inflammation is a suggested mechanism that may influence fatigue in patients with cancer, and mistletoe extract has been proposed as an intervention to reduce inflammation. Well-designed studies examining the potential effects of mistletoe extract in these areas are needed.
Bochennek, K., Balan, A., Muller-Scholden, L., Becker, M., Farowski, F., Muller, C., . . . Lehrnbecher, T. (2015). Micafungin twice weekly as antifungal prophylaxis in paediatric patients at high risk for invasive fungal disease. Journal of Antimicrobial Chemotherapy, 70, 1527–1530.
To evaluate the safety and efficacy of micafungin for antifungal prophylaxis in pediatric patients at high risk for fungal infection
Children who were intolerant to polyenes and axoles or in whom theses were otherwise contraindicated were given 3–4 mg/kg micafungin twice weekly. Micafungin was begun when the patient could not take other antifungals and was continued until hematopoetic recovery after chemotherapy or until 100 days after HCT. Trough concentrations were determined from blood drawn prior to micafungin infusion, and peak levels were obtained 30 minutes after the end of the infusion.
There was no premature discontinuation of micafungin due to related adverse events. Proven or probably invasive fungal infection did not occur in any patients.
Findings suggest that intermittent micafungin for antifungal prophylaxis can be safe and effective in high-risk pediatric patients. Additonal larger studies are needed to confirm these results.
There are a number of limitations to the use of oral triazoles for routine antifungal prophylaxis, and micfungin has been used for prevention and treatment of candida infections in children. This study showed that a larger dose, delivered intermittently, may be a safe and effective alternative for antifungal prophylaxis in high-risk children with cancer. The ability to not have to provide infusions daily can be an attractive and convenient alternative to daily treatment. This study has several important limitations, so additional well-designed research to confirm these findings in larger samples is needed.
Boccia, R.V., Gordan, L.N., Clark, G., Howell, J.D., & Grunberg, S.M. (2010). Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: A randomized, double-blind, phase III study. Supportive Care in Cancer, 19, 1609–1617.
To compare the efficacy and tolerability of the granisetron transdermal delivery system (GTDS) to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV)
Patients were randomized to oral (2 mg per day for 3–5 days) or transdermal (one GTDS patch over 7 days) granisetron before receiving multiday chemotherapy. Patients received placebo capsules or capsules according to group assignment. Corticosteroids and rescue medications were given at the discretion of the investigator. Patients were followed for 14 days after chemotherapy.
The study was conducted at multiple sites in Europe, the United States, Mexico, and India.
This was a randomized, double-blind, controlled trial.
Patients recorded the following in diaries daily.
Complete control (CC) was defined as no vomiting or retching, no more than mild nausea, and no use of rescue medication from the first administration until 24 hours after the last administration of chemotherapy.
The GTDS provided effective, well-tolerated control of CINV associated with moderately or highly emetogenic, multiday chemotherapy.
GTDS could be an option for CINV from multiday chemotherapy regimens. Further research to determine the role of this approach within an overall antiemetic regimen is warranted.
Boccia, R., O'Boyle, E., & Cooper, W. (2016). Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy. BMC Cancer, 16, 166-016-2186-4.
To establish the noninferiority of sustained-release granisetron (APF530) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) compared with palonosetron following highly emetogenic chemotherapy (HEC) and/or MEC chemotherapy in a subpopulation of patients with breast cancer, and to show the superiority of APF530 for the prevention of delayed CINV following HEC with cycle 1 of chemotherapy.
Patients were stratified based on either moderate or high emetogenicity of the chemotherapy. Patients received both IV and subcutaneous injections. Group 1 received 250 mg of APF530 subcutaneously and placebo IV, group 2 received 500 mg of APF530 subcutaneously and placebo IV, and group 3 received placebo subcutaneously and IV palonosetron 0.25 mg. APF530 was given 30 minutes prior to chemotherapy. At the completion of cycle 1, patients who received palonosetron were offered the option to remain in the study. These patients were then rerandomized 1 to 1 to receive doses of 250 versus 500 mg of APF530 subcutaneously during cycles 2–4. Treatment cycles ranged from 7 days–28 days. Rescue medications were permitted with the exception of granisetron, palonosetron, and aprepitant.
Prospective, multicenter, randomized, double-blind and double-dummy, parallel-group, phase-III noninferiority trial. Groups were broken into highly emetic and moderately emetic based on Hesketh scores.
CR rates with the experimental drug at 250 and 500 mg were not significantly different from those with palonosetron for both HEC and MEC regimens. The effectiveness of APF530 improved in later cycles, although at that point, those patients were no longer receiving palonosetron. No significant differences existed between groups in the samples. No noticeable differences existed between the breast cancer group and the overall population of the study.
Safety: Patients receiving APF530 had more complaints of injection site pain compared to palonosetron. No difference in adverse events existed between the breast cancer group and the overall population of the study.
APF530 is effective in acute and delayed CINV in patients with breast cancer. The side effect profile was similar in all arms of the study and included fatigue, constipation, and headache. The trend to better response is not a reflection of palonosetron, as this agent was not used after cycle 1.
Sustained-release granisetron can provide another alternative intervention for CINV prophylaxis; however, it does require subcutaneous injection. Further research is needed to establish the comparative effectiveness of this medication within overall CINV antiemetic regimens.
Boccia, R., Cooper, W., & O'Boyle, E. (2015). Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy. Journal of Community and Supportive Oncology, 13, 38–46.
To determine if a response to antiemetic APF530 is sustained over multiple cycles of chemotherapy
This study consisted of three treatment arms. During cycle 1, group 1 received 250 mg of subcutaneous APF530, group 2 received 500 mg of subcutaneous APF530, and group 3 received palonosetron at 0.25 mg IV in addition to an subcutaneous placebo before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Patients receiving MEC also received dexamethasone at 8 mg IV 30–90 minutes before chemotherapy. Patients receiving HEC were given 20 mg of IV dexamethasone followed by 8 mg orally twice per day on days 2–4. In cycles 2–4, palonosetron was discontinued, and all patients in the palonosetron group were randomized to receive either 250 mg or 500 mg of APF530 with dexamethasone (dosing as previously stated). Cycles were separated by a range of 3–28 days. Rescue antiemetics were allowed as needed. Local anesthetic was administered to the injection site before the study drugs were administered. Study subjects kept diaries of emetic episodes, the use of rescue medications, and the severity of nausea for each 24-hour period after receiving chemotherapy. Adverse events were documented according to standard toxicity criteria. Complete response (CR) was defined as no rescue medications and no emetic episodes. Complete control (CC) was defined as no more than mild nausea and no rescue medications. Total response was defined as no nausea and no rescue medications.
Prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trial with stratification according to the emetogenicity of regimens
In cycle 1, ≥ 75% of both doses of APF530 had acute-phase CR, and ≥ 50% had delayed-phase CR. There was a similar response rate for cycles 2–4 with the HEC group having a slightly better response than the MEC group. Acute phase CR increased over the four cycles of HEC (81%–88%) for APF530 500 mg dose and CR increased from 67% to 83% in the delayed phase for this group. In patients who received palonosetron in cycle 1, ≥ 90% of those who had CR maintained CR in subsequent cycles (with APF530). Half of the of MEC and palonosetron group that did not achieve CR in cycle 1 achieved CR in next cycle (with APF530). No treatment-related serious adverse events were seen. Common adverse events across all cycles included constipation, headache, fatigue, and diarrhea for patients who received APF530. APF530 at 250 or 500 mg caused injection site reactions. Most were mild, and greater than than 3% were moderate.
This study demonstrated sustained responses in the acute and delayed phases of chemotherapy over four cycles in both 250 mg adnd 500 mg oses of APF530. Patients who responded to APF530 in cycle 1 also responded in cycles 2–4. Patients receiving palonosetron for chemotherapy-induced nausea and vomiting had a similar response to APF530 in subsequent cycles. Patients receiving APF530 had mild adverse effects primarily related to injection site reactions.
APF530 was an effective 5HT3 blocker for the prevention of chemotherapy-induced nausea and vomiting in HEC and MEC regimens, and its efficacy was sustained over multiple cycles. There was no significant benefit in using higher doses over the 250 mg dose. There was a potential for injection site reactions caused by the subcutaneous route of APF530, which may affect patients' quality of life.
Boccia, R., Grunberg, S., Franco-Gonzales, E., Rubenstein, E., & Voisin, D. (2013). Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial. Supportive Care in Cancer, 21, 1453–1460.
To examine the efficacy of three different doses of oral palonosetron compared to IV palonosetron for chemotherapy-induced nausea and vomiting (CINV) management and to explore the contribution of dexamethasone to these regimens
Patients were randomized to one of four different groups: oral palonosetron at 0.25, 0.5, and 0.75 mg or IV palonosetron at 0.25mg. Within each of these groups, patients were randomized to receive a single 8 mg IV dose of dexamethasone or placebo. Patients were stratified by age and by whether they had received previous chemotherapy. All patients were receiving single day chemotherapy. The noninferiority margin for analysis was set at a maximum difference in complete response rate at 24 hour of 15%.
This was a multisite study conducted in outpatient settings in multiple countries.
All patients were in active antitumor treatment.
This was a randomized, double-blind, double-dummy trial.
Both oral and IV palonosetron formulations were shown to be effective in CINV prevention, and similar effects were seen at all three oral doses studied. IV palonosetron may be more effective for reduction in CINV during the delayed phase. The addition of dexamethasone was associated with improved CR rates for both acute and delayed CINV.
Findings show that effectiveness of oral and IV palonosetron is similar, though the IV formulation may be slightly more effective for prevention of CINV during the delayed phase. Findings also show that dexamethasone improves CINV control. Further research with multiday chemotherapy regimens and other emetogenic chemotherapy levels is warranted. Findings continue to show that nausea is not as well controlled as emesis. High quality assessment of CINV in both acute and delayed phases is essential to ongoing planning for the most effective antiemetic approach for individual patients. A continued need exists to find effective interventions to reduce nausea as well as emesis.
Boccardo, F.M., Ansaldi, F., Bellini, C., Accogli, S., Taddei, G., Murdaca, G., . . . Campisi, C. (2009). Prospective evaluation of a prevention protocol for lymphedema following surgery for breast cancer. Lymphology, 42(1), 1–9pr
To determine the effects of a specific protocol of prophylactic measures on the development of secondary lymphedema
The preventive protocol included preoperative upper-limb lymphscintigraphy, principles for lymphedema risk minimization, and early management of lymphedema. The positive lymphscintigraphy group underwent a microsurgical operation of lymphatic-venous multiple anastomoses at the same time of axillary nodal dissection. When postoperative lymphscintigraphy revealed disruption of blockage of arm lymphatic drainage before the onset of limb swelling, the preventive protocol group underwent early use of elastic sleeves, manual lymphatic drainage, prophylactic external compression, and remedial exercises. In case of appearance or worsening of lymphedema notwithstanding the physical methods, the patients underwent early microsurgical operation. In the control group, once a volume abnormality was determined, the standardized diagnostic and therapeutic procedures to assess and non-operatively treat lymphedema were carried out. Time points of evaluation were preoperatively and at 1, 3, 6, 12, and 24 months postoperatively.
The study took place at the University of Genoa S. Martino Hospital in Italy.
The study used a prospective randomized controlled design.
Of the 49 women with unilateral breast cancer surgery who were measured at 24 months, 10 (21%) were identified with secondary lymphedema with an incidence of 8% in the preventive protocol group and 33% in the control group. At 12 months and 24 months, the number of patients with arm volume increases was significantly lower in the preventive protocol group ( p = 0.038 and p = 0.012, respectively). There were no differences between groups at six months and no significant differences between groups at baseline in terms of risk factors.
The prophylactic strategies appear to reduce the development of secondary lymphedema and alter its progression in comparison to the control group.
The study indicates that healthcare professionals, including nurses, should inform patients with breast cancer of risk for developing lymphedema and help them understand signs and symptoms for early lymphedema. Healthcare professionals also need to examine whether patients develop lymphedema at every clinic visit. Anytime lymphedema is noted, patients should be referred for lymphedema treatment by certified lymphedema therapists or knowledgeable physical therapists. Strategies for prevention appear to be effective in the longer term.
Boccardo, F.M., Casabona, F., Friedman, D., Puglisi, M., De Cian, F., Ansaldi, F., & Campisi, C. (2011). Surgical prevention of arm lymphedema after breast cancer treatment. Annals of Surgical Oncology, 18, 2500–2505.
To assess the efficacy of lymphactic venous anastomosis (LVA) during surgery for prevention of lymphedema in women having surgery for breast cancer
Patients who consented to participation prior to surgery were randomly assigned to the intervention group or usual care. Those in the intervention group underwent the LVA microsurgical technique. Specifics of the surgery were described. In the treatment group, 16 patients had lymph node metastasis and underwent the LVA during primary surgery and axillary dissection. In those patients assigned to the intervention who did not have lymph node metastasis with intraoperative frozen section, the procedure was planned after finding micrometastasis after immunohistochemical analysis, and the LVA could be done during lymph node dissection at a second surgery. All patients had volume measurement done by the Kuhnke method and by lymphoscintigraphy. Follow-up included these measures at 1, 3, 6, 12, and 18 months after surgery.
The study was conducted in Italy. The site was not specified.
This was a randomized clinical trial.
Beginning at month three, the proportion of patients with lymphedema was higher in the control group (p = 0.047). No significant differences were reported between volume measures at baseline, one, and six months in the intervention group. By comparison, a significantly higher arm volume was reported at one and six months in the control group (p < 0.01). Postoperatively, LS demonstrated a patency rate of 95.6% for LVAs.
This trial demonstrated that intraoperative LVA microsurgery was effective in reducing arm lymphedema during the first six months after surgery in women with breast cancer.
Study findings suggested that operative LVA with breast surgery can be effective in reducing development of secondary lymphedema. More research in this area is needed to further strengthen these findings. Nurses can advocate for patients to ask about the availability and potential use of this surgical technique.