Iwase, S., Kawaguchi, T., Yotsumoto, D., Doi, T., Miyara, K., Odagiri, H., . . . Yamaguchi, T. (2016). Efficacy and safety of an amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: A multi-institutional, randomized, exploratory trial (JORTC-CAM01). Supportive Care in Cancer, 24, 637–646.
To investigate the effectiveness of a dietary supplement amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in patients with breast cancer
A dietary supplement containing branched chain amino acids coenzyme Q10 and L-carnitine was given orally once daily for 21 days at a dose of 125 g. Patients in the control group received usual care. Study assessments were conducted on day 1 and day 22, and fatigue was measured on days 8 and 15.
Fatigue initially increased from baseline to day 8 and then declined in both groups. The mean change in worst level of fatigue was greater with the intervention (p = 0.005). The mean reduction in current level of fatigue was greater with the intervention (p = 0.0009). No differences existed between groups in average feeling of fatigue or anxiety and depression scores.
The dietary supplement tested here may have some benefit in controlling fatigue among patients with breast cancer during chemotherapy.
These findings suggest that a dietary supplement of branched chain amino acids coenzyme Q10 and L-carnitine may be helpful for the management of fatigue. Further research is needed to confirm this potential.
Ito, S., Tsukiyama, I., Ando, M., Katakami, M., Hamanaka, R., Kosaka, K., . . . Kubo, A. (2015). Therapeutic and preventive antiemetic effect of aprepitant in Japanese patients with thoracic malignancies who truly need it. Supportive Care in Cancer, 23, 905–912.
To evaluate whether all patients undergoing highly emetogenic chemotherapy (HEC) need an NK1 and to evaluate the effects of aprepitant on patients who experience chemotherapy-induced nausea and vomiting (CINV) in the first course of therapy
Patients received standard antiemetics consisting of IV granisetron on day 1 and dexamethasone on days 1–3 when given highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Patients who needed aprepitant experienced CINV and received aprepitant prophylactically for the subsequent courses of chemotherapy. Other agents for rescue antiemesis were allowed. Pharmacists visited patients on days 1–6 to assist them with completing diaries to record symptoms.
Eighteen patients (23%) needed aprepitant after the first course of chemotherapy. Those receiving HEC who needed aprepitant experienced a significant improvement in the prevention of CINV (p = 0.018) and had less need for rescue medications (p = 0.001). Those receiving MEC also experienced an improvement in CINV after the use of aprepitant, although the difference was not statistically significant. Most improvement was seen in the delayed phase. Though vomiting was reduced, no significant improvement in nausea was observed. About 50% of patients required rescue antiemetics with the first course of chemotherapy.
Not all patients receiving HEC or MEC need an NK1 to prevent CINV. Aprepitant was effective in preventing vomiting in patients who had CINV during the first course of chemotherapy.
The findings suggest that all patients may not need NK1s for complete control of CINV; however, no evidence predicts which patients will or will not experience CINV without an NK1. Current guidelines recommend triplet antiemetics for HEC. Further work to identify the factors that would predict the patients who need NK1s would be helpful to potentially provide control of CINV without the high cost of NK1s.
Ito, Y., Karayama, M., Inui, N., Kuroishi, S., Nakano, H., Nakamura, Y., ... Chida, K. (2014). Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer (Amsterdam, Netherlands), 84(3), 259–264.
To evaluate the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist, and dexamethasone compared to standard therapy with a 5-HT3 receptor antagonist and dexamethasone
Chemotherapy-naïve patients receiving a carboplatin-based therapy were randomized to standard antiemetic regimens of a 5-HT3 receptor antagonist plus dexamethasone or a triple antiemetic regimen of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant.
Multi-center, randomized, open-label, parallel-group, phase-II trial
Daily questionnaire regarding the frequency of vomiting and scoring of nausea during five days. Physicians recorded any additional antiemetic therapies used during the study period.
The aprepitant group had a better overall complete response (CR) of 80% (95% CI 69%–88%); the control group had a CR rate of 67% (95% CI 55%–77%). The difference is not significant. Rescue antiemetics were given to 15% of the aprepitant group and 28% of the control group. Adding aprepitant to patients receiving carboplatin/pemetrexed (with or without bevacizumab) had an overall CR of 84% in the aprepitant group versus 57% in the control group and a 87% CR in the aprepitant group versus 59% in the control group in the delayed phase of chemotherapy. The aprepitant group had a reduced need for rescue antiemetics compared to the control group (16% versus 36%, p = 0.04). Adding aprepitant to patients receiving carboplatin/paclitaxel did not reduce the use of rescue antiemetics.
Triple antiemetic therapy did not demonstrate a significant improvement in CR and decrease in chemotherapy-induced nausea and vomiting events in the overall and delayed phases of therapy when compared to standard use of 5-HT3 and dexamethasone as an antiemetic regimen in patients with stage IIIB–IV NSCLC being treated with carboplatin-based chemotherapy (considered moderately emetogenic chemotherapy). The addition of aprepitant to the regimen of carboplatin/pemetrexed (with or without bevacizumab) improved the overall response rate and delayed phase response in addition to decreasing use of rescue antiemetics.
There may be benefit to adding aprepitant to antiemetic regimens for patients with NSCLC being treated with carboplatin/pemetrexed. This benefit was not demonstrated when aprepitant was added to carboplatin/paclitaxel regimens.
Ithimakin, S., Runglodvatana, K., Nimmannit, A., Akewanlop, C., Srimuninnimit, V., Keerativitayanan, N., . . . Laocharoenkeat, A. (2012). Randomized, double-blinded, placebo-controlled trial of ondansetron plus dexamethasone with or without metoclopramide as antiemetic prophylaxis in patients receiving high-dose cisplatin in medical practice. Supportive Care in Cancer, 20, 849-855.
To evaluate the effectiveness and safety of adding metoclopramide to the standard ondansetron and dexamethasone antiemetic regimen for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) among patients receiving cisplatin-based therapy
Patients were randomized (stratified by gender and age group) to a treatment or control group. All patients received ondansetron and dexamethasone prior to cisplatin and on the four subsequent days (days 2-5). Patients received either 20 mg of metoclopramide or placebo orally four times daily on days 2-5. Rescue treatment (including metoclopramide) was allowed based on the decision of the primary physician. On day 2, blinded data collectors documented the first emetic episode and frequency of emesis, severity of nausea and vomiting, side effects, and rescue antiemetic medications. On day 5, patients reported satisfaction of emetic treatment and quality of life.
The study was conducted at a single site, inpatient setting in Thailand.
All patients were in active antitumor treatment.
This was a randomized, double-blinded, placebo-controlled study.
No antiemetic benefit was found by adding metoclopramide to the standard ondansetron and dexamethasone regimen during cisplatin-based therapy; however, results are difficult to interpret because of a significant number of control patients receiving metoclopramide prior to the start of the study.
A high number of patients in the placebo group developed anticipatory vomiting prior to the start of treatment, which illustrates the importance of performing thorough assessments prior to the start of chemotherapy and providing education prior to the start of the next course of chemotherapy.
Israel, F.J., Parker, G., Charles, M., & Reymond, L. (2010). Lack of benefit from paracetamol (acetaminophen) for palliative cancer patients requiring high-dose strong opioids: A randomized, double-blind, placebo-controlled, crossover trial. Journal of Pain and Symptom Management, 39, 548–554.
To investigate potential analgesic benefits of 4 g paracetamol daily for palliative patients with cancer requiring high-dose opioids
Patients received usual medications plus 4 g paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries, including a numeric rating scale ranging from 0 (no pain) to 10 (unbearable pain) and recording numbers of breakthrough analgesics. Patients also indicated in which part of the study their pain was better controlled.
The study used a randomized, double-blind, placebo-controlled, crossover design.
There were no significant order or treatment-by-the-order interaction effects for any variable. There were no significant differences in pain when assessed with placebo compared with paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for a number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain.
Data from this study do not support the common practice of adding regular paracetamol (acetaminophen) daily to high-dose opioids to enhance pain control in the palliative setting.
The study had a small sample, with less than 30 participants.
There is a growing body of evidence suggesting that some patients do not receive any additional benefit from adding paracetamol or acetaminophen to strong or high-dose opioids. Pain management interventions should be individualized. Unwarranted exposure to potential side effects/toxicities and costs should be avoided when possible by eliminating paracetamol or acetaminophen in those individuals in whom no benefit has been demonstrated.
Ismail, M.A., Kamal, A.M., Ghobashy, S., Al Baz, A.G., & Roshdy, M. (2015). Comparison of pain control during Trus guided biopsies between basal peri-prostatic local infiltration anesthesia versus combined topical anal lignocaine ointment and local infiltration anesthesia. Journal of the Egyptian Society of Parasitology, 45, 285–289.
To compare two techniques for pain relief with transrectal ultrasonography (TRUS)-guided biopsies
Patients undergoing prostate biopsies were randomized to receive either local infiltration anesthesia alone or a combination of local anesthesia and lignocaine 5% ointment to the anal rind, canal, and anterior rectal wall. Patients were asked to rate pain during insertion, during infiltration, and after biopsy.
Randomized trial
Patients who received a combination of local and topical anesthesia reported significantly less pain (p = 0.005) at all stages of the procedure.
The combination of a local anesthetic infusion with a topical anesthetic may provide better pain control during biopsy.
The combination of anesthetic infiltration and a local topical anesthetic may reduce pain during biopsy.
Ishizuka, M., Nagata, H., Takagi, K., & Kubota, K. (2013). Needleless closed system does not reduce central venous catheter-related bloodstream infection: A retrospective study. International Surgery, 98, 88–93.
To determine whether a needleless closed system (NCS) is superior to the Luer cap system (LCS) in regards to the prevention of catheter-related bloodstream infection.
This was a retrospective study comparing the length of time from central venous catheter (CVC) insertion to the development of central-line associated blood stream infection (CLABSI) using LCS and then switching to NCS.
Retrospective analysis
The authors measured the time interval from CVC insertion to the development of CLABSI and compared a group of patients using LCS to a group using NCS. Centers for Disease Control (CDC) guidelines were used to define and diagnose CLABSI.
Using the Kaplan-Meier estimate and the log-rank test, the authors found that there was no significant difference between the LCS group and the NCS group in the time interval from CVC insertion to onset of CLABSI. Similarly, there was no significant difference in the incidence of CLABSI (p = 0.3), blood culture positivity (p = 0.836), and CVC tip positivity (p = 0.116) between the two groups.
There was no significant difference between the two groups in regard to blood culture positivity, CVC tip culture positivity, or the incidence of CLABSI. NCS did not demonstrate superiority in terms of prevention of CLABSI.
Although they were not shown to reduce CLABSI, NCSs are still recommended as a means of preventing needle-stick injuries.
Ishihara, M., Iihara, H., Okayasu, S., Yasuda, K., Matsuura, K., Suzui, M., & Itoh, Y. (2010). Pharmaceutical interventions facilitate premedication and prevent opioid-induced constipation and emesis in cancer patients. Supportive Care in Cancer, 18, 1531–1538.
In part 1, patients who were admitted and receiving opioids were surveyed for use of prophylactic laxatives to prevent constipation.
In part 2, prescribers were given drug information, orders were reviewed, and patients were educated about laxatives to manage constipation.
Patients were undergoing the active treatment phase of care.
This was a retrospective survey followed by an interventional study.
Laxative use prophylactically reduced the incidence of constipation in patients taking opioid therapy but did not completely prevent it.
Laxative prophylaxis is beneficial to reduce the risk of opioid-induced constipation. Proactive interventions to increase laxative use may be beneficial to patients.
Ishihara, M., Ikesue, H., Matsunaga, H., Suemaru, K., Kitaichi, K., Suetsugu, K., . . . Japanese Study Group for the Relief of Opioid-Induced Gastrointestinal Dysfunction. (2012). A multi-institutional study analyzing effect of prophylactic medication for prevention of opioid-induced gastrointestinal dysfunction. Clinical Journal of Pain, 28, 373–381.
To evaluate the effectiveness of prophylactic laxatives and antiemetics on constipation, nausea, and vomiting in patients with cancer receiving opioids for the first time.
Medical records were reviewed from 2009 to 2010 for patients experiencing constipation, nausea, or vomiting during the first week of opioid analgesic administration. Number of stools recorded was used in the analysis. Constipation was defined as a stool-free interval of at least 72 hours during the first week. One episode of vomiting was counted as evidence of vomiting. Nausea grading was recorded for seven days.
This was a descriptive, retrospective study.
National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE), version 4.0, for nausea grading
Use of prophylactic laxatives in patients receiving opioids for the first time was effective in reducing the risk and prevalence of constipation.
Findings suggested use of prophylactic laxatives can reduce opioid-induced constipation during the first week in which patients receive opioids. Findings also suggested older patients may be at greater risk for opioid-induced constipation. Nurses can ensure that prophylactic regimens to prevent constipation are suggested for patients beginning opioid use and older adult patients.
Ishido, K., Higuchi, K., Azuma, M., Sasaki, T., Tanabe, S., Katada, C., ... & Koizumi, W. (2016). Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: A randomized crossover phase II trial (KDOG 1002). Anti-Cancer Drugs, 27, 884–890.
To gain evidence regarding which regimen should be used for the management of highly emetogenic chemotherapy (HEC) induced chemotherapy-induced nausea and vomiting (CINV)
Patients were randomly assigned to the order of receiving either palonosteron and dexamethasone (PD) or aprepitant, granisetron, and dexamethasone (AGD) prophylaxis. The PD regimen was 0.75 mg palonosetron and 13.2 mg dexamethasone IV prior to treatment and 8 mg oral dexamethasone 24 and 48 hours later. The AGD regimen was 125 mg oral aprepitant and 3 mg granisetron and 6.6 mg dexamethasone IV before treatment, followed by 80 mg aprepitant and 4 mg dexamethasone at 24 and 48 hours. During the second cycle, patients were crossed over to the alternative regimen. During cycle 1, CINV and the use of rescue antiemetics were evaluated. After crossover, patients were asked which treatment was more effective and preferred. Rescue medications were metoclopramide or prochlorperazine.
No significant differences existed between treatment regimens for complete response in the acute phase. The complete response (CR) rate was higher in the delayed (p = 0.025) and overall phases (p = 0.025) in the regimen including aprepitant. Less than 40% with either treatment had no nausea. FLIE scores indicating impact on daily life showed that more patients in the aprepitant-based regimen group were not affected by nausea (p = 0.014). Forty-one percent indicated preference for AGD, 19.7% preferred PD, and 39.3% indicated no preference.
Findings suggest that a CINV prophylactic regimen containing an NK1—in this case, aprepitant—was more effective in preventing CINV than a regimen of palonosetron and dexamethasone alone.
Findings support the use of a triple drug regimen of a 5HT3, NK1, and dexamethasone for patients receiving HEC. Nausea in the delayed phase continues to be an ongoing problem that is not completely relieved with these regimens. Further research is needed to identify other adjuvant medications to address nausea.