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.
Blijlevens, N., de Chateau, M., Krivan, G., Rabitsch, W., Szomor, A., Pytlik, R., … Niederwieser, D. (2013). In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient's burden. Bone Marrow Transplantation, 48, 966–971.
To evaluate efficacy of palifermin versus placebo for prevention of oral mucositis (OM), as well as burden of patients with multiple myeloma (MM) who receive autologous stem cell transplant (SCT)
This randomized study compared three groups: (1) placebo, (2) palifermin on days -6, -5, -4, 0, 1, and 2 (pre-/post-SCT), and (3) palifermin on days 0, 1, and 2 (post-SCT). The palifermin dose was 60 µg/kg per day IV. Patients were assessed daily for OM from day 2 until day 32 or discharge.
This was a multisite, inpatient study conducted in the Netherlands.
This was a randomized, placebo-controlled, parallel-group study.
Palifermin was unable to reduce OM or OM-related patient burden in patients with MM undergoing transplant.
Short term of use of palifermin for auto-SCT in patients with MM undergoing transplant was not effective in reducing OM. The fact that authors suggest that hyperkeratosis may have been incorrectly interpreted as OM suggests that correct assessment can be an issue in evaluating this symptom. Findings suggest that the specific timing of use of this agent may be critical. In using palifermin, nurses need to be aware of the appropriate timing in concert with timing of antineoplastic treatment and treatment effects.
Blijlevens, N.M., Donnelly, J.P., Naber, A.H., Schattenberg, A.V., & DePauw, B.E. (2005). A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients. Supportive Care in Cancer, 13, 790–796.
Parenteral nutrition supplemented with 0.57 g/kg glutamine-dipeptide was started on day 6 for a median of 19 days for patients in the treatment group.
The study was conducted between July 1999 and July 2002.
This was a randomized, double-blinded, placebo-controlled pilot study.
Oral assessment was conducted daily. Lesions, erythema, edema, pain, bleeding, dryness, and the production of viscous mucous were scored on a 0–3 scale and summed to produce a daily oral mucositis score (DMS).
Bleicher, J., Bhaskara, A., Huyck, T., Constantino, S., Bardia, A., Loprinzi, C.L., Silberstein, P.T. (2008). Lorazepam, diphenhydramine, and haloperidol gel for rescue from chemotherapy-induced nausea and vomiting: Results of two pilot trials. Journal of Supportive Oncology. 6(1), 27-32.
To evaluate the efficacy of a topical gel containing lorazepam, diphenhydramine, and haloperidol (ABH), in reducing chemotherapy-induced nausea and vomiting (CINV) among patients with cancer
This article reported on two pilot trials.
Patients in one physician practice were prescribed prophylactic antiemetics according to standard guidelines. They were given a prescription for six prefilled, capped tuberculin syringes of ABH gel when they received emetogenic chemotherapy. The patients were instructed to use the ABH gel when they developed significant nausea or vomiting in the days that followed chemotherapy, with the option to repeat use at six-hour intervals. Patients were instructed to place 0.5 ml of the gel on the palmar aspects of their wrists using the prefilled syringe. After applying the gel, the participants were instructed to rub their wrists together gently for one to three minutes to facilitate transdermal absorption.
In the first trial, an investigator contacted patients by telephone within one month. Patients provided verbal informed consent at this time. The investigator asked patients questions about their progress with ABH gels using a standard questionnaire, developed for the pilot. Patients were asked to rate their CINV and if they believed the gel to cause sedation, skin irritation, or muscle spasms.
In the second trial, after patients provided verbal consent, an investigator used a structured interview by telephone or in person to rate the severity of CINV on a combined scale at 30 minutes and fours hours after applying the ABH gel.
The trials were conducted at the outpatient clinic of a university in the midwestern United States.
Transdermal ABH gel decreased the severity of CINV with only slight sedation reported.
Use of transdermal ABH is convenient and easily taught to patients; however, availability of this combination topical agent may be a challenge in community settings because hospital pharmacies are less likely to compound products.
Blazer, M., Phillips, G., Reardon, J., Efries, D., Smith, Y., Weatherby, L., … Bekaii-Saab, T. (2012). Antiemetic control with palonosetron in patients with gastrointestinal cancer receiving a fluoropyrimidine-based regimen in addition to either irinotecan or oxaliplatin: a retrospective study. Oncology, 83, 135–140.
To evaluate the use of palonosetron compared to ondansetron for the complete control of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic oxaliplatin or irinotecan plus a fluoropyrimidine regimen
Patient charts were reviewed for time periods before the use of palonosetron and after use of palonosetron. Prior to use of palonosetron, ondaansetron was given in combination with 12 mg oral dexamethasone 30 minutes prior to chemotherapy on day 1 of each regimen. In the post palonosetron group, palonosetron was used instead of ondansetron. In the setting of grade 1 or more vomiting or grade 2 nausea, aprepitant was added to the regimen. Nurses graded nausea and vomiting during chemotherapy administration.
This was a single-site study conducted in both the inpatient and outpatient settings of a Midwest (Ohio) Academic medical center.
This study was a retrospective review of patients’ medical records.
With the use of palononsetron, the incidence of CINV failure was 28.4% versus 50.3% with the use of ondansetron (p < 0.001) regardless of the agent used (oxaliplatin or irinotecan).
The findings of this study support the use of palonosetron in regimens that include oxaliplatin or irinotecan plus either 5-FU or capecitabine. The study reported that the use of palononsetron resulted in a statistically significant reduction in the risk of CINV.
Although the National Comprehensive Cancer Network (NCCN) Guidelines for Antiemesis state that, for moderately emetogenic chemotherapy, a 5-HT3 antagonist and dexamethasone should be used to prevent CINV, this study showed that, for regimens with oxaliplatin or irinotecan and either 5-FU or capecitabine, the 5-HT3 of choice may be palononsetron. What is unknown is whether the use of palononsetron is equally as effective in reducing CINV using other moderately emetogenic chemotherapeutic regimens.
Blanchard, D., Bollet, M., Dreyer, C., Binczak, M., Calmels, P., Couturaud, C., ... & Albert, S. (2014). Management of somatic pain induced by head and neck cancer treatment: Pain following radiation therapy and chemotherapy. Guidelines of the French Otorhinolaryngology Head and Neck Surgery Society (SFORL). European Annals of Otorhinolaryngology, Head and Neck Diseases, 131, 253–256.
PHASE OF CARE: Active antitumor treatment
Many systematic reviews were used as references such as the Cochrane Library, but no number articles reviewed or how these were chosen were mentioned. Selection was based on each reviewer’s experience.
The categorization using the ANAES guides to determine level of evidence and grades was appropriate. However, the search methods used in these guidelines were not clearly stated and need reconfirmation because there was no way to know whether the search was comprehensive. The recommendations were grade B and expert opinions.