Noor, R., Bedikian, A. Y., Mahoney, S., Bassett, R., Jr., Kim, K., Papadopoulos, N., … Homsi, J. (2012). Comparison of two dosing schedules of palonosetron for the prevention of nausea and vomiting due to interleukin-2-based biochemotherapy. Supportive Care in Cancer, 20, 2583–2588.
To compare efficacy of two dosing schedules of palonosetron for prevention of nausea and vomiting caused by interleukin-2- (IL2) based biochemotherapy
Patients who were treatment naïve were randomized to one of two dosing schedules for 0.25 mg IV palonosetron for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). Schedule one was on days 1 and 4, and schedule two was on days 1, 3, and 5. All patients received the same chemotherapy/biotherapy regimen, which consisted of dacarbazine on day 1; cisplatin, vinblastine, and IL-2 on days 1-4; and interferon (IFN) alpha 2b on days 1–5 as part of a 21-day cycle. Patients also received 0.5–1 mg IV lorazepam every 8 hours. Rescue medications were 50 mg IV metoclopramide with 25 mg IV diphenhydramine every 4 hours, 10 mg IV prochlorperazine every 4 hours, or a combination of lorazepam, diphenhydramine, and haloperidol compounded in hospital pharmacy. An episode of nausea or vomiting was defined as nausea or vomiting of any severity reported by the patient or documented by the nursing staff at any time during the 21-day treatment cycle as well as the need for rescue medication during the first 7 days. Patient diaries were used to document episodes of nausea and vomiting and the antiemetic used to control them. Function Living Index-Emesis (FLIE) was used to assess the patient’s quality of life daily for days 1–7.
This was a single site, inpatient study conducted at the M.D. Anderson Cancer Center in Houston, TX.
Patients were undergoing the active treatment phase of care.
This was a randomized, two-group, comparison study.
Each group (schedule 1 and schedule 2) had 15 patients. For the first 7 days of treatment, more episodes of nausea were reported for schedule 1 than schedule 2, but the difference was not statistically significant (p = 0.16). A similar trend was observed when comparing the number of episodes of emesis during the first 7 days (p = 0.20), the number of antiemetic rescue doses required (p = 0.30), and number of episodes of nausea and emesis during the first 21 days. Evaluation of the FLIE revealed similar proportion of patients on schedule 1 and 2 experiencing interference with appetite, sleep, physical activity, social life, and enjoyment of life (p = 0.071).
Because of the small sample size, differences in dosing schedule efficacy cannot be determined with confidence. However, a trend toward better control of CINV was noted with more frequent palonosetron dosing.
Corticosteroids for the prevention of biochemotherapy-induced nausea and vomiting are contraindicated because they cause lysis of lymphokine-activated killer (LAK) cells produced in response to IL-2, which makes control of CINV challenging. This study does not provide evidence to support use of antiemetic schedule 1 versus schedule 2. More research is needed.
Nong, L., Sun, Y., Tian, Y., Li, H., & Li, H. (2013). Effects of parecoxib on morphine analgesia after gynecology tumor operation: A randomized trial of parecoxib used in postsurgical pain management. The Journal of Surgical Research, 183, 821–826.
To investigate the influence of parecoxib on morphine analgesia after gynecological tumor surgery
The test group (group P) was given 40 mg IV parecoxib prior to induction of anesthesia and 40 mg IV q 12 hours for 48 hours after the operation. The control group (group C) was given 2 ml saline at the same time intervals. Both groups were introduced to a patient-controlled analgesia (PCA) device and documentation of postoperative pain or adverse effects on Visual Analog Scale (VAS).
Placebo-controlled, randomized, controlled trial
There was a reduction of about 9% in the total morphine requirement used within the first 48 hours after gynecological tumor surgery, and overall satisfaction scores were 8.6 versus 6.8 (groups P and C, respectively). Pain scores at rest and with movement were significantly lower in the parecoxib group at all postoperative time points (p < .001).
The use of parecoxib with patient-controlled analgesic morphine in postoperative analgesia resulted in enhanced analgesic efficacy, reducing the opioid requirement, increasing patient satisfaction, and reducing pain severity after gynecological tumor surgery.
This study has positive implications for nursing and healthcare professionals as it did show a 9% decrease in morphine PCA use in the first 48 hours postoperatively with fewer reported side effects. This study should be replicated with a larger sample size to validate its findings.
Nomura, M., Kamata, M., Kojima, H., Hayashi, K., & Sawada, S. (2013). Irsogladine maleate reduces the incidence of fluorouracil-based chemotherapy-induced oral mucositis. Annals of Oncology, 24, 1062-1066.
To evaluate the effects of irsogladine maleate (IM) on fluorouracil-induced oral mucositis
Patients were randomly assigned to irsogladin maleate (IM) or placebo or normal saline. Treatment was administered orally twice a day, 4 mg/day beginning on the first day of chemotherapy and continued for 14 days. Oral rinse with sodium gualenate hydrate, standard care was also used 4 times daily. Other oral treatments were not allowed. Patients were assessed on days 1, 3, 5, 8, 10, 12, 14, 21, and at the end of the chemotherapy cycle.
The sample was comprised of 66 patients. Age in the IM arm: 35-79, in the placebo arm 30-79 .
MALES (%) IM arm n = 20 and placebo arm n = 21; FEMALES (%) IM arm n = 13 and placebo n = 12.
KEY DISEASE CHARACTERISTICS: 83% of all patients had tumors in the head and neck or esophagus.
OTHER KEY SAMPLE CHARACTERISTICS: Most patients had stage III-IV tumors. Chemotherapy included 5FU and cisplatin or nedaplatin.
SITE: Single site
SETTING TYPE: Inpatient
LOCATION: Kansai Medical University, Hirakata, Japan
PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Elder care
Double blind randomized placebo controlled
WHO grading of oral mucositis
NCI – CTCAE
Incidence of oral mucositis was 27.3% in the IM group and 72.7% in the placebo group (hazard ratio 0.14, 95% CI 0.05-0.42, p < 0.001). Changes in oral mucositis showed that severity scores were significantly lower in the IM group on multiple study days (p < 0.05). No adverse events related to IM were found.
This study adds to the evidence suggesting that IM is useful in the prevention of oral mucositis.
Small sample (<100)
Key sample group differences that could influence results
Other limitations/*explanation: There is no information regarding patient adherence to the protocol for frequency of medication use.
This study showed that irsogladine maleate use was associated with reduced incidence and severity of oral mucositis in these patients receiving chemotherapy associated with development of mucositis. There are few treatments that have been shown to be effective for mucositis prophylaxis. Given the promising results in this relatively small study, further research is warranted.
Nishioka, M., Shimada, M., Kurita, N., Iwata, T., Morimoto, S., Yoshikawa, K., . . . Kono, T. (2011). The Kampo medicine, Goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen. International Journal of Clinical Oncology, 16, 322-327.
To clarify the efficacy of Goshajinkigan (GJG) for peripheral neuropathy associated with oxaliplatin
Intervention Studies: From January 2007 through December 2009, 45 patients with advanced or recurrent colorectal cancer who were being treated with 5-fluorouracil, oxaliplatin, and leucovorin (FOLFOX) every two weeks participated in the study. Patients were randomized to receive either oral GJG (7.5 g/daily) or no drug. The median number of cycles was 13 for the patients in the GJG group and 12 for the control group. Neuropathy was evaluated during every course according to the Neurotoxicity Criteria of Debiopharm. Other neuromodulatory agents such as calcium and magnesium infusions were not allowed during the study. Oxaliplatin dose was reduced in the event of grade 3 neuropathy.
Prospective, randomized, controlled trial
Patients were evaluated at baseline and during their every-two-weeks treatment course according to the Neurotoxicity Criteria of Debiopharm.
The incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group (p < 0.01, log-rank test). The incidence of grade 3 peripheral neuropathy after 10 courses was 0% in the GJG group and 12% in the control group. After 20 courses, it was 33% in the GJG group and 75% in the control group. The only differences in adverse effects between the two groups were peripheral neuropathy and influence on tumor response.
A randomized, double-blind, placebo-controlled trial would be needed to determine efficacy of this oriental herbal medication. No trials with GJG have been conducted in the United States, so no history exists of it being used as an intervention for chemotherapy-induced peripheral neuropathy. These preliminary findings suggest that further research in use of GJG may be warranted.
Although it has shown some positive results in reducing neuropathy in a clinical trial in Japan, GJG can not be recommended for treating chemotherapy-induced peripheral neuropathy in the United States until further testing occurs in a large, randomized, double-blind study.
Nishimura, J., Satoh, T., Fukunaga, M., Takemoto, H., Nakata, K., Ide, Y., . . . Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO). (2015). Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): A multicentre, randomised, controlled phase 3 trial. European Journal of Cancer, 51, 1274–1282.
To evaluate the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) for in patients with colorectal cancer receiving oxaliplatin
PHASE OF CARE: Active anti-tumor treatment
This was a double-blind, randomized, placebo-controlled trial.
Patients used a diary on days 1–6 to record the use of rescue antiemetics, severity of nausea, and episodes of vomiting. The severity of nausea was recorded on a four-grade scale. Tolerability, or other adverse effects, were monitored through laboratory tests and a physical examination.
For patients receiving oxaliplatin for the treatment of colorectal cancer, CINV prophylaxis with aprepitant or fosaprepitant significantly reduced the rate of vomiting in the acute and delayed phases and significantly reduced the rate of nausea in the delayed phase.
Aprepritant and fosaprepitant are safe and effective for the prevention of CINV in patients with colorectal cancer who receive oxaliplatin.
Nishihara, M., Arai, Y.C., Yamamoto, Y., Nishida, K., Arakawa, M., Ushida, T., & Ikeuchi, M. (2013). Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable, painful bone metastases. Pain Physician, 16, E547–E552.
To see if a combination of low-dose antidepressants and antiepileptic is effective in treatment of pain from bone metastases
Patients were randomized to one of three groups: pregabalin 50 mg every 8 hours (P), pregabalin 25 mg every 8 hours and imipramine 5 mg every 12 hours (PI), or pregabalin 25 mg every 8 hours and mirtazapine 7.5 mg every 12 hours (PM). Assessments were done at baseline and daily between days 1–7 and on days 10–14.
Total pain scores decreased significantly on day 1 in all groups (p < .05). By day 2, pain scores declined significantly more in the PI and PM groups and remained essentially stable and consistently lower than the P group (p < .05). A few patients developed dizziness and mild drowsiness. No changes were seen in electrocardiograms.
The combination of low-dose pregabalin and low-dose antidepressant significantly reduced pain in this study.
Findings suggest that the combination of low-dose antidepressant and antiepileptic medication as adjuncts to opioids and bisphosphonates may improve pain control in patients with intractable pain from bone metastases. This type of combination may be worth trial in patients with this type of pain. Nurses should be aware of the potential for drug-drug interactions in patients taking multiple medications. This potential may be less with low doses, as used in this study.
Niscola, P., Scaramucci, L., Giovannini, M., Ales, M., Bondanini, F., Cupelli, L., et al. (2009). Palifermin in the management of mucositis in hematological malignancies: Current evidences and future perspectives. Cardiovascular & Hematological Agents in Medicinal Chemistry, 7, 305–312.
To review the role of palifermin and other current and potential treatments for chemotherapy-induced mucositis in the context of pathobiology in hematologic malignancies
Database searched was MEDLINE. Abstracts and published proceedings reporting the role of palifermin in the management of mucositis were reviewed.
Search keywords were MeSH headings for chemotherapy, cyclophosphamide, etoposide, GI mucositis, GVHD, hematology, hematological malignancies, hematopoeietic stem cell transplantation, hemorrhagic cystitis, HSCT, keratinocyte growth factor, KGF, leukemia, lymphoma, melphalan, methotrexate, mucositis, multiple myeloma, oncohematology, oral mucositis, pain, palifermin, radiation, radiotherapy, soreness, and total parenteral nutrition.
Palifermin in standard and high dose chemotherapy
Palifermin in autologous stem cell transplantation
Palfiermin in graft-versus-host disease
Other interventions for management of mucositis
Control of oral mucositis pain and provision of supportive therapy and regular assessment are critical management components.
This article provided information about various approaches in the management and prevention of oral mucositis in patients with hematologic malignancies and outlined the biologic mechanism of action and observed effects from review of the literature. However, it provided little information about the actual strength of evidence and is based on a limited literature search. No clear description of rationale for article inclusion was included.
The authors concluded that evidence supports the use of palifermin, but the article stated elsewhere that evidence in this area is insufficient in some patient groups, and only one nonrandomized study is cited where the duration of high-grade mucositis was shorter in patients who received palifermin, suggesting a biased view of the role of palifermin.
This article can provide useful information regarding the mechanism of action of various treatments, but it is not helpful in determining relative effectiveness of various interventions.
Nikoletti, S., Hyde, S., Shaw, T., Myers, H., & Kristjanson, L.J. (2005). Comparison of plain ice and flavored ice for preventing oral mucositis associated with the use of 5-fluorouracil. Journal of Clinical Nursing, 14, 750–753.
To evaluate the use of plain ice, flavored ice, and standard care in the management of oral mucositis
Patients receiving 5-fluorouracil (5-FU) were randomized to receive standard care plus plain ice, standard care plus flavored ice, or standard care alone. Standard care alone consisted of mouthwashes of plain or salty water four times daily plus use of a soft toothbrush and nonabrasive toothpaste. Patients who were assigned to one of the cryotherapy arms were instructed to swirl the ice around the mouth for five minutes prior to, five minutes during, and 20 minutes after the injection. Patients who used plain ice were instructed to do so three times daily. Flavored ice was in the form of a purchased product called \"icy poles.\" Nurses assessed mucositis prior to each chemotherapy cycle and 15 days after each intervention. The sequencing of the interventions was random.
The study was conducted in an outpatient, chemotherapy, acute care setting at a teaching hospital in Australia.
This was a randomized, controlled, crossover trial.
Nikander, E., Metsa-Heikkila, M., Ylikorkala, O., & Tiitinen, A. (2004). Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of Clinical Endocrinology and Metabolism, 89, 1207–1212.
The study explored the effects of daily use of isoflavonoids on climacteric symptoms and QOL in postmenopausal women who had been treated for breast cancer.
Phytoestrogen tablets and similar-looking placebo tablets (six tablets per day) were taken every 12 hours with a glass of water. The participants were seen at the research center before and after each treatment period. Sixty-two postmenopausal, symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for three months; the treatment regimens were reversed after a 2-month washout period.
Six women discontinued the trial for various reasons during the first phase. Thus, 56 women completed the study. The mean age pf participants was 54 (± 6 years).
This was a randomized placebo-controlled crossover trial of phytoestrogens in treatment of menopause in breast cancer participants.
At each visit, the participants were interviewed about hot flashes and other typical climacteric symptoms using the Kupperman index and Menopausal Visual Analogue scale. Blood levels of phytoestrogens, FSH, LH, estradiol, and sex hormone-binding globulin, liver enzymes, and creatinine levels were followed. Compliance with treatment was confirmed by diary records and by measurement of serum phytoestrogen levels.
The use of phytoestrogens led to significant rises in the levels of phytoestrogens, whereas the placebo regimen had no effect. Kupperman indexes at the end of treatment with phytoestrogen or placebo did not differ. Hot flashes and the other components of the Kupperman index were not relieved by the phytoestrogen regimen when evaluated separately.
Pure isoflavonoids at a dose of 114 mg for three months did not relieve hot flashes or other menopausal symptoms in participants with breast cancer
Potential limitations of the trial included:
Nightingale, C.L., Rodriguez, C., & Carnaby, G. (2013). The impact of music interventions on anxiety for adult cancer patients: A meta-analysis and systematic review. Integrative Cancer Therapies.
To clarify the effect of music interventions on anxiety for adult patients with cancer from rigorously conducted studies
TYPE OF STUDY: Meta-analysis and systematic review
Patients were undergoing active antitumor treatment.
Length of the intervention varied substantially from 5 minutes to 4 hours. There was high variability in the number of sessions delivered. Most studies examined a single intervention with immediate pre and post anxiety measurement. Three delivered live music, 1 involved a music therapist, and 11 involved listening to music via headphones. Meta-analysis showed no significant difference between the music intervention and controls (SMD = -0.003 (95% CI -0.51, 0.52).
Meta-analysis showed no significant effect of music interventions on anxiety in adults with cancer.
Results of this analysis do not support an effect of music interventions on anxiety in adults with cancer.