Cuesta-Vargas, A.I., Buchan, J., & Arroyo-Morales, M. (2014). A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors. European Journal of Cancer Care, 23, 15–21.
To assess feasibility and effectiveness of aquatic-based exercise in the form of deep water running as part of a multimodal physiotherapy program for breast cancer survivors in an effort to decrease cancer-related fatigue
Eight week program of one hour sessions, three times per week, of multimodal physiotherapy program combined with deep water running delivered by physiotherapists in groups of 8–10 participants. Each session included 30 minutes of land-based exercise, followed by 20 minutes of deep water running.
Statistically significant differences in fatigue were found between groups after eight weeks, with the intervention group reporting greater improvement in behavioral severity, affective/meaning, and sensory fatigue.
Demonstrated positive effects of exercise on cancer-related fatigue. Supports prior studies that demonstrated greater improvement combining educational and exercise programs
This is a difficult program to replicate, but it appears that it is likely to be effective in reducing cancer-related fatigue.
Cubero, D.I., & del Giglio, A. (2010). Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: A prospective, randomized, double-blind, placebo-controlled study. Supportive Care in Cancer, 18, 235–242.
To evaluate the efficacy of methadone as a substitute for morphine, and to investigate whether the addition of acetaminophen improves pain control in switching to methadone
Patients using morphine for oncologic pain who were on a stable dose for at least one week were recruited. Patients were rapidly switched to oral methadone without a transition period and randomized to receive acetaminophen or placebo with methadone for seven days. The daily morphine dose was converted to methadone in ratios according to the total daily morphine dose. In case of additional pain, patients were instructed to use extra methadone no more than every two hours using a dose equal to 25% of the total daily dose. Use of coanalgesics such as anti-inflammatory drugs, antidepressants, and neuroleptics was allowed. Pain intensity was evaluated daily and recorded by patients in a diary along with all analgesic medications used. Patients were followed for seven days.
The study design was double-blind, randomized, placebo-controlled for use of acetaminophen, and open label for switch to methadone.
Of the original study sample, 16% ended participation early due to treatment failure with intense pain, somnolence, or vomiting. Most patients who completed the study had a significant improvement in pain by the faces (p = 0.05) and numeric (p = 0.03) rating scales. There were no differences between patients who did and did not receive acetaminophen.
Study findings show that most patients can be switched from morphine to methadone with no transition period, with some improvement in side effects of constipation and xerostomia and adequate pain control. The addition of acetaminophen in this process was of no benefit.
This study shows that patients can be rapidly switched from morphine to methadone; however, this approach failed in 16% of patients. Methadone may be associated with less constipation and dry mouth, and may be a good pain control option for patients with these problems. Acetaminophen did not improve pain control with this switching process.
Cruz, F.M., de Iracema Gomes Cubero, D., Taranto, P., Lerner, T., Lera, A. T., da Costa Miranda, M., … del Giglio, A. (2012). Gabapentin for the prevention of chemotherapy-induced nausea and vomiting: A pilot study. Supportive Care in Cancer, 20, 601–606.
To evaluate the efficacy and safety of gabapentin for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately or highly emetogenic chemotherapy
Chemotherapy naïve patients with cancer who were scheduled to begin moderately or highly emetogenic chemotherapy were randomized to either receive 300 mg gabapentin or a placebo, in addition to a standard regimen of antiemetic prophylaxis (8 mg IV ondansetron, 10 mg IV dexamethasone, and 50 mg IV ranitidine before chemotherapy on day 1 and 4 mg oral dexamethasone twice a day on days 2 and 3).
Patients received either the gabapentin or the placebo five and four days before chemotherapy, once per day; three and two days before chemotherapy, twice per day; and one day before through five days after chemotherapy, three times per day. After chemotherapy was administered until the morning of day 5, patients kept diaries to record episodes of emesis or retching and severity of nausea over the previous 24 hours.
The primary outcome of this study was an evaluation of the number of patients reporting a complete response (CR), defined as the absence of nausea and vomiting and no use of rescue medications, during three timeframes.
The study was conducted at a single site at a large medical institution in Brazil.
All patients were in active treatment.
This was a randomized, double-blind, placebo-controlled trial.
Gabapentin may be a low-cost, nausea prophylaxis medication that can be used as an alternative to more expensive antiemetic medications. Although the authors described gabapentin as a low-risk medication, recent reports have linked gabapentin to increased rates of depression and suicide. It also has been commonly associated with the side-effects of drowsiness and dizziness.
For patients who are uninsured or underinsured and those living in developing countries where obtaining high-cost medications may be difficult, gabapentin may prove useful as a less-expensive alternative antiemetic prophylactic medication. Research should attempt to compare less expensive alternatives with current best practices.
Cruz, L.B., Ribeiro, A.S., Rech, A., Rosa, L.G., Castro, C.G., & Brunetto, A.L. (2007). Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Pediatric Blood and Cancer, 48(4), 435–440.
780 nm 60 mW 4 J/cm2 was applied uniformly to five areas of the oral cavity for five consecutive days from initiation of chemotherapy.
The sample was pediatric patients (some with HSCT) receiving a variety of chemotherapies.
Laser group: n = 29
Control group: n = 31
The study ran from May 2003-February 2005.
RCT was the study design.
CTC-NCI
Nutritional Status Assessment
Day 8,15
Day 8 results: 13 patients in the laser group and 7 patients in the control group with mucositis; median grade of mucositis was 2 for the laser group and 1 for the control group (p = 0.234)
Day 15 results: 13 patients in the laser group and 11 patients in the control group with mucositis; median grade of mucositis was 1 in both groups; prevalence and severity were similar (p = 0.208)
Almost identical prevalence of mucositis and other findings; no evidence to support laser for prevention
Rigorous oral care may have masked results.
Optimal timing of laser treatment is unknown.
Small sample
Cruciani, M., Malena, M., Bosco, O., Nardi, S., Serpelloni, G., & Mengoli, C. (2003). Reappraisal with meta-analysis of the addition of gram-positive prophylaxis to fluoroquinolone in neutropenic patients. Journal of Clinical Oncology, 21, 4127–4137.
To compare prophylaxis with a fluoroquinolone (ciprofloxacin, ofloxacin, perfloxacin, or norfloxacin) in combination with an antibiotic against gram-positive bacteria (penicillins, macrolide, rifampin, or vancomycin) compared to fluoroquinolone alone in neutropenic patients with cancer
DATABASES USED: MEDLINE, CANCERLIT, Database of Abstracts of Reviews of Effects, and Cochrane Library (1984–2002); the bibliographies of retrieved studies also were reviewed.
The addition of gram-positive prophylaxis to fluoroquinolones reduced
No difference was found between gram-positive prophylaxis and a fluoroquinolone compared with a fluoroquinolone alone with regard to
However, adding gram-positive prophylaxis significantly increased the occurrence of side effects, primarily gastrointestinal intolerance and liver function test abnormalities seen with rifampin and roxithromycin.
The authors concluded that the evidence does not support routine use of gram-positive coverage in combination with a fluoroquinolone for antibacterial prophylaxis in neutropenic patients with cancer.
Cruciani, M., Rampazzo, R., Malena, M., Lazzarini, L., Todeschini, G., Messori, A., & Concia, E. (1996). Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: A meta-analysis. Clinical Infectious Diseases, 23, 795–805.
DATABASES USED: MEDLINE was searched for literature published from January 1984–October 1994. Current Contents also was used, as were the bibliographies from MEDLINE articles.
KEYWORDS: Key words used in the search were neutropenia/agranulocytosis and bacterial infections.
INCLUSION CRITERIA: Eligible studies were randomized, controlled trials with fluoroquinolones alone or in combination with gram-positive prophylaxis in granulocytopenic patients receiving chemotherapy for cancer.
Prophylaxis with fluoroquinolones alone was shown to significantly reduce the frequency of gram-negative bacteremia. No significant difference was found in terms of gram-positive bacteremia or infection-related mortality. Fluoroquinolone with gram-positive prophylaxis significantly reduced the frequency of gram-positive bacteremia. Fever-related morbidity and infection-related mortality were not affected. Of note, the majority of the studies (four of six) used fluoroquinolone alone in the control group.
Cruciani, R. A., Dvorkin, E., Homel, P., Malamud, S., Culliney, B., Lapin, J., . . . Esteban-Cruciani, N. (2006). Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. Journal of Pain and Symptom Management, 32, 551–559.
Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous L-carnitine may hold promise as a treatment for this symptom. Carnitine was prepared by the institutional pharmacy at a concentration of 1 g/mL. The drug was administered in two daily doses for seven days. After the intervention period, patients were allowed to continue L-carnitine supplementation if desired. Patient outcomes were evaluated at baseline and on day seven.
Beth Israel Medical Center Continuum Hospice Care, Jacob Perlow Hospice, or the Cancer Center
Patients were undergoing the active treatment phase of care.
The study was an open-label, phase I/II clinical trial.
Brief Fatigue Inventory (BFI)
Patients who received the L-carnitine intervention experienced a significant decline in fatigue (p < 0.001) as BFI scores decreased from baseline (66.1 [standard deviation (SD) = 12]) to one week after treatment to (39.7 [SD = 26]).
Cruciani, R. A., Dvorkin, E., Homel, P., Culliney, B., Malamud, S., Shaiova, L., . . . Esteban-Cruciani, N. (2004). L-carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Annals of the New York Academy of Sciences, 1033, 168–176.
Carnitine is hypothesized to be key in the energy metabolism and regulation of adenosine triphosphate (ATP) promotion and a protective effect of mitochondrial metabolism. Carnitine deficits are common in cancer patients and other chronically ill persons.
L-carnitine supplementation was given in dose levels of 250 mg/day. Dose levels were planned to increase by 500 mg until the target dose of 3000 mg/day was reached.
Of 645 adult patients, 13% met following inclusion criteria:
Patients were excluded from the study if they had severe disease, brain tumor, or stroke; were unable to complete the assessment tools; had started erythropoietin within less than 3 months; had received radiotherapy or chemotherapy within one week prior to the study; or were unable to consent.
Hospice and Cancer Center
The study used an open-label, dose-finding, safety design, with dose cohorts of three.
Cost of supplements and monitoring levels of L-carnitine is unknown.
Cruciani, R. A., Zhang, J. J., Manola, J., Cella, D., Ansari, B., & Fisch, M. J. (2012). L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern Cooperative Oncology Group phase III, randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology, 30, 3864–3869.
To determine the efficacy of L-carnitine supplementation for fatigue in patients with cancer.
Patients were randomized to receive 1 g of L-carnitine liquid twice daily for four weeks or placebo. For weeks five to eight, all patients received L-carnitine in an open-label extension. Outcome measures were assessed at baseline and at weeks four and eight.
Patients were undergoing the active antitumor treatment phase of care.
The study was a randomized, double-blind, placebo-controlled, phase III trial followed by a four-week open-label extension.
The group receiving L-carnitine had a greater increase in plasma carnitine levels. At week four, one-third of those on placebo were carnitine-deficient, compared to 11% of those who were receiving carnitine (p ≤ 0.001). BFI scores improved significantly in both groups by approximately one point (p < 0.001). There were no differences between groups in fatigue, depression, or pain. Over time, there was a significant decrease in the proportion of patients with severe fatigue, pain, and depression; however, there were no significant differences between groups. There were few high-grade toxicities. In one patient, the cause of death was possibly related to treatment.
Supplementation of 1 g of L-carnitine did not improve fatigue, pain, or depression in these patients.
Of the patients, 25% to 30% had missing outcome data; however, power analysis showed that the sample size was sufficient.
The findings showed that dietary supplementation with L-carnitine did not improve fatigue, depression, or pain in patients with cancer. Nurses can advise patients that this approach has not been shown to be helpful, as these results provide strong evidence that L-carnitine is not effective for these symptoms.
Cronfalk, B.S., Ternestedt, B., & Strang, P. (2010). Soft tissue massage: Early intervention for relatives whose family members died in palliative cancer care. Journal of Clinical Nursing, 19, 1040–1048.
To explore how bereaved relatives experienced early intervention with soft tissue massage during the first four months since the death of a family member who received palliative cancer care
Study data resulted from two interactions with Swedish-speaking relatives of deceased patients with cancer who had received care in a large palliative care unit. Demographic and baseline data were collected in an initial 60-minute visit to the relative. Hand or foot soft tissue massage, which is defined as a gentle but firm movement of the skin that activates touch receptors, was done in slow strokes, light pressure, and circling movement using lightly scented vegetable oil.
One week after an eight-week intervention involving either protocol-driven or relative election of either hand or foot soft tissue massage, the first author audiotaped hour-long interviews with the 18 study participants. Open-ended interviews focused on the experience of receiving the massages via a dialectical validation approach to ensure understanding of relatives’ experience. The authors supported trustworthiness and qualitative credibility factors during interviews and data analysis processes based on interview transcriptions and close attention text. An additional follow-up telephone call six to eight months after the interview was intended to encourage participants to reflect on their current life situation in relation to the grieving process.
A prospective, descriptive, qualitative design was used.
A qualitative content analysis allowed various levels of interpretation and abstraction to support one predominant theme: Bereaved relatives felt “feelings of consolation and help in learning to restructure everyday life.” The theme derived from four categories: (a) a helping hand at the right time, (b) something to rely on, (c) moments of rest, and (d) moments of retaining energy. Overall, soft tissue massage supported relatives’ need for comfort, as well as hope during a difficult transition time for relatives who sought a balance of grieving and moving on with their lives after the death of a loved one. No analysis of the follow-up telephone conversations appeared in the article.
Early interventions for relatives who grieve the loss of a family member’s death, including sequential soft tissue hand or foot massage, may facilitate relatives’ feelings of belonging, human connection to healthcare staff who cared for their family member before death, sense of self, and energy to structure life after a family member’s death. Too often, delayed interventions cause unnecessary worry and suffering of bereaving relatives. The offering of soft tissue massage to those relatives at a desired time may constitute a cost-effective way to support bereaved relatives early in their grieving process.
Early support, including that inherent in the delivery of soft tissue massage, to grieving relatives of a family member who died from cancer or other chronic illnesses, offers a cost-effective intervention that may improve the health of those relatives. This intervention needs further testing to determine its efficacy but does highlight the importance of grieving relatives reconnecting with the healthcare professional, physical touch, and getting needed support. Further research with diverse populations in other global communities may extend understanding and acceptance of this potentially future intervention to add quality-of-life care to relatives and other family members. Testing of a soft tissue massage intervention could support evidence for the effectiveness of this intervention and nurses’ referral of caregivers to this intervention for improved quality of life.