Moryl, N., Kogan, M., Comfort, C., & Obbens, E. (2005). Methadone in the treatment of pain and terminal delirium in advanced cancer patients. Palliative and Supportive Care, 3, 311–317.
To document the use of methadone as part of an opioid-rotation strategy for the treatment of uncontrolled pain in patients with delirium at the end of life
Ten patients rotated from morphine, five from fentanyl, two from hydromorphone, and three from fentanyl-morphine or morphine- hydromorphone combinations. Authors were purposefully conservative in calculating the starting methadone dose. Within the first week four patients expired, one changed to IV methadone, and two rotated back to morphine because of worsening delirium and inadequate analgesia. At two weeks, 10 patients had expired. Of the remaining 10, seven stayed on methadone. The average dose was 1.1 mg/hour. Two patients returned to morphine, and one was rotated to Percocet.
United States
Nonrandomized open-label prospective study
Pain control was significant in 15 of 20 patients; average analgesia was good to excellent. Sedation rating decreased from 1.65 to 0.55 on 1–3 scale. Cognitive status improved for nine patients. Six patients achieved moderate improvement in cognitive status; two, partial improvement; and three, no improvement. Three days after the switch from an opiod, average MDAS score improved from 23.6 to 10.6. Decreased alertness on methadone was devoid of agitation.
Methadone can be an acceptable alternative to an opioid in the treatment of refractory pain and terminal delirium. The use of methadone can minimize the need for sedation to treat delirium.
Mortimer, J.E., Lauman, M.K., Tan, B., Dempsey, C.L., Shillington, A.C., & Hutchins, K.S. (2003). Pyridoxine treatment and prevention of hand-and-foot syndrome in patients receiving capecitabine. Journal of Oncology Pharmacy Practice, 9, 161–166.
To evaluate the effectiveness of oral pyridoxine for preventing and treating palmar plantar erythrodysesthesia (PPE) associated with capecitabine
Of the patients receiving oral pyridoxine, 73 patients (74%) received it as prophylaxis, and the remainder (26%) received it as acute hand-foot syndrome (HFS) treatment. The median dose of pyridoxine was 200 mg/m2.
The data did not support that vitamin B6 prophylaxis prevented overall PPE incidence in a greater proportion of patients compared with those who did not receive prophylaxis (60% versus 53%). However, when used as treatment, a greater proportion of patients receiving vitamin B6 reported symptom improvement (65% versus 12%, p < 0.001).
Pyridoxine is not recommended for prophylaxis but may provide some relief for patients with acute HFS.
Morrow, G. R., Hickok, J. T., Roscoe, J. A., Raubertas, R. F., Andrews, P. L., Flynn, P. J., . . . University of Rochester Cancer Center Community Clinical Oncology Program. (2003). Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. Journal of Clinical Oncology, 21, 4635–4641
Patients were given oral paroxetine 20 mg orally daily or placebo for eight weeks.
18 Community Clinical Oncology Program (CCOP) outpatient centers
Patients were undergoing the active treatment phase of care.
The study was a randomized, double-blind, placebo-controlled trial.
The paroxetine group and the placebo control had comparable levels of fatigue and depression at study inception. Paroxetine had neither beneficial nor detrimental effects on fatigue. There was a significantly lower mean level of depression in the paroxetine group compared with the placebo group. Treatment with paroxetine also favorably affected patients’ general moods. There were no differences in the effect of paroxetine on fatigue by gender, age, indication for treatment (adjuvant treatment versus treatment for metastatic disease), or by whether patients were more or less fatigued at baseline.
No special training is required to deliver the intervention. There are costs related to drug acquisition.
Morrow, G. R., Schwartzberg, L., Barbour, S. Y., Ballinari, G., Thorn, M. D., & Cox, D. (2014). Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: A multistudy analysis. The Journal of Community and Supportive Oncology, 12, 250–258.
To compare the efficacy and safety of palonosetron with older 5HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea
Data were pooled from four studies that were multicenter, randomized, double-blinded clinical trials comparing palonosetron, ondansetron, dolasetron, or granisetron.
The patients treated with palonosetron experienced less nausea each day then the other 5HT3 RAs, and fewer patients receiving palonosetron had moderate to severe nausea. The use of rescue medication was less frequent among patients in the palonosetron arm. The complete control rates for palonosetron versus older 5HT3 RAs were 66% versus 63% during the acute acute phase, 52% versus 42% in the delayed phase, and 46% versus 37% in the overall phase. No safety differences or concerns were noted.
Palonosetron was more effective in treating and preventing nausea than ondansetron, dolasetron, and granisetron. All four agents tolerated equally well.
Nurses are aware that palonosetron has a longer half-life and is the medication of choice for outpatient treatment. This study reinforces palonosetron use by noting that more patients receiving it had nausea-free days, lower nausea ratings, and less rescue medication use. Nausea is very subjective, but nurses are aware that it is more of a problem in the delayed phase than actual vomiting. Nausea affects quality of life, and this study can help nurses choose the correct 5HT3 RA.
Morotti, M., Menada, M.V., Boccardo, F., Ferrero, S., Casabona, F., Villa, G., . . . Papadia, A. (2013). Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer. International Journal of Gynecological Cancer, 23, 769–774.
To describe the use of microsurgical lymphatic venous anastomosis (LVA) to prevent lower limb lymphedema (LLL) in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND)
The intervention group underwent the LVA procedure. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). For the intervention group, circumferential measurements were assessed at preoperation, at drain removal, at eight weeks and four months postsurgery, and during routinely follow-up examinations. A lymphoscintigraphy was performed one month postsurgery. For the control group, circumferential measurements were taken at routine cancer surveillance examinations. Lymphoscintigraphies were performed at variable intervals of time from the surgery.
In the study group, four patients underwent bilateral ILND, and four patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean time required to perform a monolateral LVA was 23.1 minutes (SD = 3.6; range, 17–32 minutes). The mean follow-up was 16.7 months (SD = 6.2); there was only one case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (p = 0.092).
This study shows, for the first time, the feasibility of LVA in patients with vulvar cancer undergoing ILND. Although no significant difference noticed in lymphoscintigraphy at one month postsurgery, a trend toward a smaller mean of transport index was noted in the study group. Future studies with larger samples sizes are needed.
The study provides nurses with updated information about potential feasibility and early clinical outcome of LVA in patients with vulvar cancer undergoing ILND. However, the small sample size, non-randomized, controlled trial design, as well as short follow-up do not allow the researchers to draw definitive conclusions on the effectiveness of LVA technique in this population. Future large, long-term follow-up randomized, controlled trials are warranted.
Mori, T., Hasegawa, K., Okabe, A., Tsujimura, N., Kawata, Y., Yashima, T., … Okamoto, S. (2008). Efficacy of mouth rinse in preventing oral mucositis in patients receiving high-dose cytarabine for allogeneic hematopoietic stem cell transplantation. International Journal of Hematology, 88, 583–587.
To determine efficacy of an icy mouth rinse during the administration of cytarabine
Patients were instructed to rinse the mouth with ice-cold water every 10 minutes during the two-hour cytarabine infusion and for one hour after completion of cytarabine infusion. At each time, patients were instructed to rinse the mouth three times. Oral mucositis grading was evaluated daily from the day treatment began to day 28 post-transplant or until complete resolution of mucositis. Maximum grades were used in analysis.
The study was conducted at a single-site inpatient setting in Tokyo, Japan.
This was a prospective trial with comparison to historical controls.
The National Cancer Institute common toxicity criteria grading for mucositis was used.
Incidence of grade 2 mucositis (p = 0.009) and grade 3 mucositis (p = 0.02) was significantly lower in patients who used the mouth rinse compared to the historical controls.
Findings suggest that the cytarabine excreted into saliva contributes to high-dose, cytarabine-induced oral mucositis. Approaches such as mouth rinsing may remove this from the oral cavity and help in the prevention of severe mucositis. How the temperature of the rinse may influence effects is not known.
Use of ice water rinses during chemotherapy infusion is a simple intervention that might be helpful for prevention of oral mucositis. Well-designed research in this area is warranted, and application and timing of use with other chemotherapeutic agents needs to be examined.
Mori, T., Yamazaki, R., Aisa, Y., Nakazato, T., Kudo, M., Yashima, T., … Okamoto, S. (2006). Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer, 4, 392–395.
To determine if shorter duration of cryotherapy would minimize side effects without affecting efficacy
Patients were instructed to use cryotherapy 15 minutes before, for 15 minutes during, and for an additional 30 minutes after receiving high-dose melphalan infusion (140 mg/m2). The cryotherapy consisted of continuously swirling ice chips in the mouth and gargling with and swallowing ice-cold water every 10-20 minutes throughout a total of 60 minutes. These patients were compared to 18 historical controls who used cryotherapy for 120 minutes. The 17 patients in the study received fludarabine 25 mg/m2 daily for five days and melphalan 70 mg/m2 per day over 15 minutes for two days, two days prior to hematopoietic stem cell transplantation (HSCT). Some patients received additional chemotherapy or radiation therapy.
The National Cancer Institute (NCI) common toxicity criteria (CTC) were used to evaluate stomatitis.
Two of the 17 patients in the study (11.1%) developed grades 2–3 oral mucositis, compared to two out of 18 historical controls (11%) who used cryotherapy for a longer time period. Although this is not a statistically significant difference, patients in the study group did report significantly lower incidence of unpleasant symptoms compared to those in the historical control group (p < 0.001).
This article provided an interesting discussion and rationale for adjusting the length of oral cryotherapy to relieve patient discomfort.
The sample size was small, and this was not a controlled study.
Moreno, V.V., Vidal, J.B., Alemany, H.M., Salvia, A.S., Serentill, M.L., Montero, I.C., . . . Padró, J.G. (2006). Prevention of irinotecan associated diarrhea by intestinal alkalization. A pilot study in gastrointestinal cancer patients. Clinical and Translational Oncology, 8, 208–212.
Two grams of powdered NaHCO3 diluted in 250 ml water was sipped during the days of irinotecan administration, starting in the morning. Other fluids were taken ad lib.
Four of 24 patients (16%) had grade III–IV diarrhea (8 had prior pelvic radiation therapy, a risk factor associated with diarrhea). Comparison was made to incidence of grade II–IV diarrhea in previous colorectal cancer studies. The researchers’ conclusion was that intestinal alkalization may be effective in preventing diarrhea with patients with gastrointestinal cancer receiving irinotecan.
Morel, V., Joly, D., Villatte, C., Dubray, C., Durando, X., Daulhac, L., . . . Pickering, G. (2016). Memantine before mastectomy prevents post-surgery pain: A randomized, blinded clinical trial in surgical patients. PLOS One,11(4), e0152741.
To determine if pre- and postmastectomy treatment with memantine can prevent neuropathic pain, impaired cognition, and decreased quality of life (QOL)
Memantine 5–20 mg or placebo was given daily for four weeks starting two weeks prior to mastectomy, with increasing doses during the first two weeks prior to mastectomy and maintained at 20 mg during two weeks after surgery. The control received placebo daily for four weeks starting two weeks prior to mastectomy. Assessment was baseline, two weeks prior to surgery, two weeks after surgery, and three and six months postop.
A significant reduction in pain at three months postoperatively was noted (p = 0.017) and better ability to cope with pain was demonstrated (p = 0.032). No significant difference was noted at six months. Secondary outcomes for pain intensity showed no significant difference. A significant difference existed in use of antiepileptics for pain at M3 which was maintained up to M6 (M3, p = 0.04; M6, p = 0.04) with overall significant time difference (p = 0.041). Pain was significantly less for those receiving chemotherapy at M3 (p = 0.04) and M6 (p = 0.009). In addition, chemotherapy-induced paresthesias/dysesthsias was significantly reduced at M3 compared to the day of inclusion (p = 0.01). No significant difference was noted in cognitive function or QOL. No significant difference was noted in regards to LSEQ; however, significance was noted for behavior following wakefulness at M6 (p = 0.038).
Memantine can potentially reduce post-mastectomy and chemotherapy-induced nerve pain while limiting polypharmacy and comorbidity associated with the current treatment approach. This approach would need to be demonstrated in a larger population, with a longer term follow-up and potential dosing change.
Nurses would need to be educated on use of memantine for pain control and the potential side effects. Patient education would be required to help the patients understand the use of this medication for treatment of pain. Results of the effects of this approach may be limited.
Morean, D.F., O'Dwyer, L., & Cherney, L.R. (2015). Therapies for cognitive deficits associated with chemotherapy for breast cancer: A systematic review of objective outcomes. Archives of Physical Medicine and Rehabilitation, 96, 1880–1897.
PHASE OF CARE: Late effects and survivorship
Studies of pharmacologic interventions were not found to be effective in improving cognitive function. Medications reviewed included d-methylphenidate (n = 1), epoetin alfa (n = 2), and ginkgo biloba (n = 1). Evidence for nonpharmacologic interventions was mixed. No improvements in cognitive function were found with Tibetan sound meditation (n = 1). Natural restorative therapy (n = 1) improved attention only when comparing the baseline with the final 90-day evaluation (p = 0.01). Exercise (n = 1) improved attention (p = 0.019) and verbal memory (p = 0.048) but not working memory. Cognitive rehabilitation (n = 1) improved four out of six measures of information processing speed (p < 0.05) but not attention, verbal memory, or executive function. Cognitive behavioral training (n = 2) improved verbal memory (p < 0.05) in both studies and was effective in improving in information processing speed when compared to baseline scores in one study (p ≤ 0.01) but not the other. Computerized cognitive training was effective in one study in improving processing speed (p = 0.009), executive function (p = 0.008), and a measure of executive function and language (p = 0.003) but not verbal memory. However, in another study, there was no difference in verbal memory or information processing speed between the intervention and control groups.
Nonpharmacologic interventions, especially cognitive training, may have a role for improving attention, information processing speed, and verbal memory. Exercise and computerized cognitive training may be effective for improving executive function. However, additional research validating these findings with larger sample sizes and evaluating other cognitive domains is needed. In addition, studies determining the dose or duration of interventions is required for a durable response.
These findings suggest that nonpharmacologic, not pharmacologic, interventions may be helpful in managing chemotherapy-induced cognitive impairment in patients with breast cancer. However, these findings were based on a small number of studies per intervention. Additional research validating which interventions might be useful in improving cognitive impairments in women receiving chemotherapy for breast cancer is needed.