Ananda-Rajah, M.R., Grigg, A., Downey, M.T., Bajel, A., Spelman, T., Cheng, A., . . . Slavin, M.A. (2012). Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period. Haematologica, 97, 459–463.
The study analyzed the relative effectiveness and safety of azole antifungal prophylaxis with particular attention to the tri-azoles compared to fluconazole/itraconazole.
Patients at the Royal Melbourne Hospital with AML/MDS undergoing remission-induction chemotherapy from December 1998–January 2010 who received one day or more of azole prophylaxis were included. Prophylaxis consisted of fluconazole 400 mg daily, itraconazole sodium 2.5 mg/kg twice daily, voriconazole 200 mg twice daily or posaconazole 200 mg three times daily with fatty food. These were started 1–2 days prior to chemotherapy and continued until neutrophil recovery (greater than 0.5 cells/L), occurrence of a confirmed or suspected invasive fungal infection, drug-related toxicity/intolerance, or the patient’s condition becoming palliative. Oral administration was preferred, fluconazole or voriconazole could be given via IV when a patient’s gastrointestinal absorption was considered inadequate.
216 patients were evaluated (57 in the fluconazole group, 59 in the itraconazole group, 82 in the voriconazole group, and 68 in the posaconazole group).
The median age per group was: fluconazole, 57 (range = 20–79); itraconazole, 55 (range = 20–79); voriconazole, 51 (range = 17–81); posaconazole, 51 (range = 19–78).
Regarding key disease characteristics, 197 patients had AML and 18 had transformed MDS. Median duration of neutropenia ranged from 13–16 days.
Patient receiving TPN per group: fluconazole, 38%; itraconazole, 40%; voriconazole, 21%; posaconazole, 31%.
Fluconazole was used from December 1998 to September 2008, itraconazole was used from May 1999 to January 2003, voriconazole was used from November 2002 to August 2008, posaconazole was used from September 2006 to January 2010.
Active antitumor treatment
The study was a retrospective review.
The majority of patients (213/216) underwent chemotherapy for remission-induction or re-induction or relapsed disease. The median duration of neutropenia for fluconazole/itraconazole was significantly longer than voriconazole/posaconazole (16 days versus 14 days, p = 0.003). TPN requirement was 39% versus 26% (p = 0.001), and median duration of prophylaxis was 18 days versus 22 days (p < 0.001).
Breakthrough invasive fungal infection occurred in 27 patients comprising of probable/proven (11) and possible (16). The incidence of breakthrough invasive fungal infection was significantly lower in the voriconazole/posaconazole group (10 of 125; 8%) versus fluconazole/itraconazole (17 of 85; 20%) (p = 0.011). All probable/proven invasive fungal infections were molds, most commonly aspergillosis.
Sub-therapeutic drug levels were common in itraconazole (42%), voriconazole (38%), and posaconazole (69%).
In this institution, the use of voriconazole/posaconazole coincided with a significant decrease in the incidence of breakthrough invasive fungal infections.
Risk of bias:
*Findings generalizable to only hematologic malignancies. The retrospective nature is not as strong in this study and, although some good information was shared, the results are not as useful to change practice.
This study compared different agents used for antifungal prophylaxis. There is always the need for education of patients and staff of the signs on infection while on prophylactic therapy and the education of taking the medication correctly and changing to an alternate therapy if the risk of impaired gastrointestinal function is greater for particular patients (i.e., severe mucositis).
An, L.X., Chen, X., Ren, X.J., & Wu, H.F. (2014). Electro-acupuncture decreases postoperative pain and improves recovery in patients undergoing a supratentorial craniotomy. The American Journal of Chinese Medicine, 42, 1099–1109.
To determine if electro-acupuncture (EA) is an effective adjunct treatment to manage postoperative pain, nausea, vomiting (PONV), and recovery in patients after a supratentorial tumor resection
In group A, acupuncture needles were inserted into the LI4, SJ5, BL63, LR3, ST36, and BG40 points, then EA stimulation was used with frequencies of 2 and 100 Hz alternating every three seconds at a level of maximum tolerance for each patient. The duration of the intervention was from the induction of anesthesia till the surgery ended. In group C, no needle was inserted.
After six hours of surgery, the Visual Analog Scale scores, the mean total bolus administration, and the effective number of PCIA bolus administrations in the EA group was statistically significantly lower than the control group. During the 6–48 hours, there were no differences in the mean total bolus administration, the effective number of bolus administrations, and the total fentanyl dose between the two groups. There were no differences in PONV between the two groups. Patients in the EA group experienced a lower incidence and degree of dizziness and feelings of fullness in the head compared to patients in the control group. Patients in the EA group could eat more on a liquid diet than patients in the control group 24 hours postoperatively.
EA can reduce postoperative pain, decrease the number of effective PCIA bolus administrations, improve appetite, and decrease dizziness and feelings of fullness in the head for patients who received supratentorial tumor resections.
These study findings show that EA may be used as an adjunct treatment to reduce postoperative pain, decrease the number of effective PCIA bolus administrations, improve appetite, and decrease dizziness and feelings of fullness in the head for patients receiving supratentorial tumor resections.
Amr, Y.M., & Yousef, A.A. (2010). Evaluation of efficacy of the perioperative administration of venlafaxine or gabapentin on acute and chronic postmastectomy pain. The Clinical Journal of Pain, 26, 381–385.
To investigate the analgesic efficacy of venlafaxine and gabapentin on acute and chronic pain after breast cancer surgery
Patients were randomized prior to surgery to one of three groups. The venlafaxine group received 37.5 mg of extended release venlafaxine once daily and a second placebo capsule at bedtime. The gabapentin group received 300 mg of gabapentin daily and another placebo capsule at bedtime, and the placebo group received placebo capsules daily and at bedtime. Medications were started the evening before surgery and continued for the first 10 postoperative days. Anesthesia was standardized. When patients complained of pain in recovery they were given a titrated dose of morphine until the VAS pain score was 30 or less. For the first 24 hours postoperatively, IV morphine at 20–50 mcg/kg was given to maintain Visual Analog Scale (VAS) at or below 30. For the remaining time to postoperative day 10, all patients were given acetaminophen and codeine every six hours and as necessary. Pain scores were recorded at rest and with movement at four, 12, and 24 hours on the first postoperative day, then daily for 10 days, then six months later.
Double-blinded, randomized, placebo-controlled trial
Compared to the control group, VAS scores from the second to the tenth day postoperatively were significantly lower in the gabapentin group (p < 0.0003). Compared to controls, VAS scores for pain with movement were significantly reduced for those receiving venlafaxine during days 8–10 (p < 0.0002). Total morphine consumption in the first 24 hours was lower in the gabapentin group compared to both other groups (p < 0.0001). Significantly more patients in the control and gabapentin groups were using opioids for pain at six months (p < 0.05). There were differences among groups in the type of pain reported at six months, but there were no consistent or significant differences in overall pain results. Patients who received venlafaxine had lower prevalence of burning and stabbing or pricking pain. There were no differences between groups in terms of side effects.
The perioperative administration of gabapentin was associated with decreased pain during the acute phase after breast cancer surgery, but it did not appear to have an effect on the incidence of chronic pain after six months postoperatively. The administration of perioperative venlafaxine may have had a beneficial effect on chronic postmastectomy pain syndrome.
The findings of this study showed that perioperative gabapentin was associated with reduced pain in the acute postoperative period among women with breast cancer. The use of venlafaxine may have some benefit for long-term neuropathic pain postmastectomy, but these findings were not definitive. This adds to a growing body of evidence regarding the efficacy of gabapentin in reducing acute surgical pain and points to the need for additional research regarding interventions and the potential role of venlafaxine for postmastectomy pain syndrome.
Amodeo, L., Castelli, L., Leombruni, P., Cipriani, D., Biancofiore, A., & Torta, R. (2011). Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: A pilot study. Supportive Care in Cancer, 20, 375–384.
To compare the tolerability and efficacy of two different titrations of paroxetine in a population of patients with cancer who have depression
Patients who were randomized to slow up-titration started paroxetine 2.5 mg/day, increasing the daily dose by 2.5 mg each third day, until 10 mg/day was reached on day 8. On day 9, the dosage was increased to 15 mg/day, and on day 11, patients reached the full dose of 20 mg/day.
Patients who were randomized to standard up-titration started with 10 mg/day of paroxetine and increased the daily dose to 20 mg/day on day 8.
Open randomized trial
Both treatment groups showed a significant mood improvement. A significantly higher rate of patients in the slow up-titration group2, compared to the standard titration group, showed no side effects after two weeks (p = 0.005). A total of 46.7% of subjects used in the intent-to-treat analysis were considered responders, according to MADRS results. Nine patients (30%) dropped out because of side effects that included gastrointestinal problems, dizziness, confusion, restlessness, and tremors. The majority of side effects appeared within the first two weeks.
Slow paroxetine up-titration is better tolerated and at least as effective as the standard paroxetine up-titration in patients with cancer who have depression. Fewer than half the patients in the final sample were identified as responders to treatment, and a third discontinued the treatment because of the drug's side effects.
Slow up-titration is better tolerated and may support patient compliance.
A large proportion of patients had side effects that caused them to discontinue treatment. In the general population, side effects from antidepressants are associated with discontinuation of treatment. In patients with cancer who may already have significant symptom burden, the benefits of antidepressant treatment need to be considered in this context.
Among patients with cancer, it is not yet clear which patients actually benefit from medication to counter depressive symptoms.
Ames, S.C., Tan, W.W., Ames, G.E., Stone, R.L., Rizzo, T.D., Jr., Crook, J.E., . . . Rummans, T.A. (2011). A pilot investigation of a multidisciplinary quality of life intervention for men with biochemical recurrence of prostate cancer. Psycho-Oncology, 20, 435–440.
To evaluate the acceptability and estimate the effect size of a multidisciplinary quality-of-life intervention for men with biochemical recurrence of prostate cancer
The intervention involved eight multidisciplinary group sessions consisting of education, goal setting, relaxation training, problem solving, social support, physical activity, and mood management.
Biochemical relapse phase
A randomized controlled trial design was used.
The results did not provide strong support for a meaningful effect of the intervention provided here on anxiety or quality of life in patients with biochemical recurrence of prostate cancer. Findings suggest that this type of intervention is acceptable to the patient population, since there was a high rate of attendance.
Given the lack of durability, the intense, multidisciplinary nature of this intervention may not be the best use of limited resources. Further, such a multidisciplinary intervention may be difficult to replicate in the community setting.
Miaskowski, C., Cleary, J., Burney, R., Coyne, P., Foster, R., Grossman, S., . . . Zahrbock, C. (2005). Guideline for the management of cancer pain in adults and children. APS Clinical Practice Guidelines Series. Glenview, IL: American Pain Society.
PROCESS OF DEVELOPMENT: An interdisciplinary panel of experts in cancer pain management prepared these guidelines. When unavailable, recommendations were not made or were made on the recommendation of experts in that area.
Amara, S. (2008). Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy. Annals of Pharmacotherapy, 42, 1481–1485.
The purpose of the study was to determine what role glutamine plays in preventing peripheral neuropathy.
The author searched PubMed from 1990 to May 2008 with the key words glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkloids. To be included, studies had to evaluate the role of oral glutamine in preventing and treating chemotherapy-induced peripheral neuropathy (CIPN). Studies were excluded if they used glutamine in the reduction of other radiation or chemotherapy-induced related toxicities such as mucositis, cardiotoxicity, diarrhea, and cachexia.
Three clinical trials were reviewed for sample, inclusion/exclusion criteria, study design, and results given. No type of measurement was used to review the study quality. Of note, the article did not state if other studies were found in the literature review.
Study 1 suggested that glutamine helps to decrease symptoms of peripheral neuropathy. Study 2 suggested that glutamine can help prevent some symptoms of CIPN. And, finally, study 3 suggested that glutamine may reduce the occurrence of CPIN.
Although each study had a small sample size, glutamine did appear to help reduce symptoms of neuropathy. However, the systematic review concluded that a lack of sufficient evidence existed to recommend oral glutamine for the prevention of CIPN. Glutamine could be beneficial in patients receiving high-dose paclitaxel and oxaliplatin.
The safety and tolerability of glutamine was not mentioned.
Amar, D., Grant, F.M., Zhang, H., Boland, P.J., Leung, D.H., & Healey, J.A. (2003). Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery. Anesthesiology, 98, 337–342.
To determine if e amino-caproic acid (EACA) will reduce perioperative blood loss in patients with cancer undergoing orthopedic surgery (intraoperative plus 48 hours)
Blood loss and RBC units transfused did not differ. The two treated groups had a significantly lower D-dimer level (P < 0.01).
Amadori, F., Bardellini, E., Conti, G., Pedrini, N., Schumacher, R.F., & Majorana, A. (2016). Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: A randomized double-blind controlled study. Lasers in Medical Science, 31, 1231–1236.
To evaluate the efficacy of low-level laser therapy (LLLT) to reduce the severity of chemotherapy-related oral mucositis in children
Patients were randomized to receive LLLT or sham control interventions. Therapy began on day 1 of diagnosis of oral mucositis and was continued daily for the next three days. Study assessments were done immediately before beginning laser therapy, on day 4 after completion of laser therapy, and on day 7. Individuals who applied the laser treatment were not involved in mucositis data collection.
Progressive decline in mucositis severity occurred in both groups, and no significant difference in grading existed between groups. Pain scores were lower in those treated with laser therapy (p < 0.05), and those getting LLLT required less analgesia.
The findings suggested that LLLT may help the management of pain from oral mucositis among children receiving chemotherapy.
The findings did not show the efficacy of LLLT among children to reduce the severity of oral mucositis. Further well-designed research is needed to determine if a role exists for LLLT in children receiving chemotherapy.
Alvarez, J., Meyer, F. L., Granoff, D. L., & Lundy, A. (2013). The effect of EEG biofeedback on reducing postcancer cognitive impairment. Integrative Cancer Therapies, 12, 475–487.
To determine the feasibility of using electroencephalography (EEG) biofeedback (neurofeedback) and identify its potential effects on cognitive impairment, sleep quality, fatigue, and psychological symptoms.
Neurofeedback was provided using an EEG system that detects and alerts the brain of phase changes to increase brain flexibility and resilience. Single EEG sensors, placed at the left C3 and right C4 for each brain hemisphere, analyze EEG activity for identification of phase state changes in the brain. During the session, the patient listened to music while sitting quietly; brief interruptions of the music signal alerted the patient that the software detected phase changes and was providing the brain feedback. No patient response or action was required because it is believed that the brain uses the feedback for its own self-organization without conscious action. Patients had twice weekly sessions for 10 weeks. Assessments were performed prior to beginning the sessions and during the fourth, seventh, and tenth week of sessions.
The study was conducted at a single outpatient site in Ohio.
The study has clinical applicability for late effects and survivorship.
The study used a feasibility quasiexperimental design.
Significant symptom presence and dysfunction were reported by this sample at baseline, as compared to normative data. Baseline comparisons to normative sample showed significant differences from the norms in all measures, indicating significant dysfunction. FACT, FACIT, and PSQI scores improved over time, although not at a constant rate over longitudinal time points. At study conclusion, symptom report of dysfunction no longer differed significantly from normative populations on three of four FACT-C subscales, FACIT, and PSQI. The proportion of patients using sleep medications declined from 39% to 17% by study conclusion. No adverse effects of the intervention were identified.
EEG neurofeedback was shown to be feasible and potentially beneficial for improving cognitive function, sleep, and fatigue in breast cancer survivors.
This study reported a potentially promising intervention that may have a positive effect on several symptoms experienced by breast cancer survivors. Additional well-designed clinical trials are needed to assess the efficacy of this approach.