DOI Link: doi: 10.3109/09638288.2013.774441

STUDY PURPOSE: To summarize evidence regarding rehabilitation interventions to address problems of cancer survivors

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed, EMBASE, CINAHL, Scopus, Google Scholar

INCLUSION CRITERIA: Effectiveness of treatment that could be provided by rehab professionals, subjects 18 years or older, cancer survivors (defined as having completed primary treatment). Reports on only systematic reviews and RCTs, though these were not identified as criteria.  

EXCLUSION CRITERIA: Pharmaceutical, surgical, or radiological interventions

TOTAL REFERENCES RETRIEVED: Not stated

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No quality rating applied. Appears to have very few studies in multiple areas.

• FINAL NUMBER STUDIES INCLUDED =  56
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not provided
• KEY SAMPLE CHARACTERISTICS: Not provided

PHASE OF CARE: Transition phase after active treatment

• Reviews seven systematic reviews and six RCTs regarding impact of exercise on fatigue
• States that results confirm a positive effect on fatigue for rehab therapies
• Some of these studies included acupuncture, counseling, and mindfulness-based stress reduction therapy

Evidence supports the effectiveness of exercise-based interventions in managing fatigue among cancer survivors.

• No quality rating of studies
• Limited studies included, and it is not clear how these were selected
• Study findings are grouped by problem, rather than synthesizing evidence related to specific interventions (for example, combining effects of exercise and acupuncture interventions)

The review provides limited information to assess efficacy of specific interventions. Studies reviewed here do not add further to the body of knowledge overall, and the report is aimed at identifying interventions that can be provided by rehabilitation professionals rather than synthesis of intervention evidence.

• The author described the pathophysiology of palmar-plantar erythrodysesthesia (PPE) and strategies to prevent or minimize PPE.
  • Pegylated liposomal doxorubicin leaks out of abnormally formed (i.e., tumor-related), damaged, or dilated blood vessels.
  • Because the hands and feet contain a high concentration of blood vessels, they are particularly susceptible to PPE.
  • Patients should avoid any undue pressure to their skin caused by running, gardening, crossing their legs, leaning on their elbows, or wearing shoes or clothing that is too tight or rubs the skin.
  • In addition, patients should avoid activities that dilate the blood vessels, such as sitting in the sun, ingesting hot fluids or food, and taking hot showers or baths.
• The author provided a nursing algorithm for the management of hand-foot syndrome.
  • Provide patient education prior to chemotherapy.
  • Review causes and symptoms of PPE.
  • Avoid undue pressure to the skin (i.e., wear loose clothing and shoes).
  • Avoid dilation of blood vessels (e.g., hot showers, sun).
  • Report all symptoms.
• Manage symptoms of PPE as required.
  • Advise patients to use cold packs.
  • Advise patients to elevate extremities to reduce edema.
  • Suggest topical emollients (e.g., lanolin creams, Bag Balm^®).
  • Suggest burn ointments (e.g., silver sulfadiazine).
  • Initiate administration of oral pyridoxine (100–300 mg per day).
  • Prescribe systemic pain medications, as required.
  • Teach wound care to prevent infection.
  • Reinforce patient education, emphasizing prevention.

Multiple interventions can be implemented to prevent or minimize PPE. Patient education is an integral component to promote self-care. Key teaching points include strategies for patients to avoid pressure and friction on their skin because those behaviors may increase uptake of the affecting drug into the blood vessels of the hands and feet.

Routine assessment for PPE should include examination of the palms and soles for redness, swelling, flaking, blisters, rash, sores, cracks, and fissures. Based on nursing assessment, dose modifications may be needed.

DOI Link: doi: 10.1002/hon.2133

To verify the efficacy of cryotherapy plus low level laser therapy (LLLT) on oral mucositis (OM) in patients receiving high-dose melphalan chemotherapy

Prior to chemotherapy, patients were examined by a dentist who performed prophylaxis, eliminated any oral infections, and provided oral hygiene instructions. All patients received basic oral care, consisting of gargling with alcohol-free mouthwash and brushing of teeth. Daily LLLT was given from the day after chemotherapy was begun until engraftment. Study group patients also received cryotherapy in addition to LLLT with ice chips for five minutes before infusion, during melphalan infusion, and then for 30 minutes after infusion. Mucositis was evaluated daily. Patients who received cryotherapy were compared to historical controls who received only oral hygiene and historical controls who received hygiene plus LLLT.

• N = 104
• MEAN AGE = 56.3 years
• AGE RANGE = 6–73 years
• MALES: 70.2%, FEMALES: 29.8%
• KEY DISEASE CHARACTERISTICS: Patients had multiple tumor types, most had multiple myeloma, and all were undergoing ablative chemotherapy for HCT.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority had autologous HCT.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Brazil

• PHASE OF CARE: Active antitumor treatment

• Prospective with historical cohort comparisons

• World Health Organization (WHO) oral mucositis scale

Fifty-four patients had LLLT plus cryotherapy, 17 had LLLT, and 33 had only oral hygiene. All patients had some degree of OM. Those who received LLLT plus cryotherapy had the highest prevalence of grade 1 mucositis and lowest prevalence of grade 2 or greater (p < 0.001). The duration of OM was highest in the control group, who had only oral hygiene (p < 0.001).

The combination of LLLT and cryotherapy was associated with the lowest severity of OM compared to controls and patients receiving LLLT alone.

• Baseline sample/group differences of import
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Significant group differences in age, chemotherapy regimens used, and diagnoses, which could have influenced results

The addition of oral cryotherapy to LLLT for patients undergoing ablative chemotherapy with melphalan prior to HCT demonstrated greater efficacy in reducing the severity of OM. Both LLLT and cryotherapy have demonstrated efficacy for preventing severe OM. This study shows that the addition of oral cryotherapy with melphalan infusions can further reduce this complication. Nurses should employ cryotherapy in appropriate patients such as those receiving high-dose melphalan, and advocate for the concomitant use of LLLT.

DOI Link: doi:10.1016/j.ejon.2011.05.001

PURPOSE: To review effective strategies to assist nurses in caring for patients receiving sorafenib, with the focus on those adverse effects the group felt were most difficult to manage—hand-foot syndrome, diarrhea, fatigue, and oral complications

TYPES OF PATIENTS ADDRESSED: Patients receiving sorafenib for renal cell or hepatocellular cancer

RESOURCE TYPE: Evidence-based guideline

DATABASES USED: PubMed, Cochrane Library, and hand-searching of the Clinical Journal of Oncology Nursing and American Society of Clinical Oncology website     

KEYWORDS: Side effect general terms, and specific terms for each side effect (e.g., altered taste, hand-foot syndrome); disease-related search terms included renal cancer, cancer of the kidneys, hepatocellular carcinoma, and liver cancer

INCLUSION CRITERIA: Evidence base included wider literature regarding the management of similar adverse events in patients with other types of cancer and other types of antitumor therapy. No other specific criteria were stated.

EXCLUSION CRITERIA: Not stated
 

• PHASE OF CARE: Active antitumor treatment            
• APPLICATIONS: Late effects and survivorship

Out of 2,469 initial citations retrieved, 37 were included for review. No specific quality evaluation of citations was done due to the nature of the literature, with few clinical trials. No description of the group process used is provided. Findings from citations reviewed were outlined and a review of the literature was provided, but no actual synthesis of evidence exists. Noted is that most evidence in this area is from experience.

Recommendations for mucositis include oral care, amifostine, and antibiotic paste for prophylaxis. For symptom management, recommendations include ice chips, topical lidocaine solutions, sage tea and baking soda oral rinses, and topical solution containing aloe vera, and advising patient to avoid tobacco, alcohol, and spicy foods, mucosal coating agents (e.g., Gelclair®), hydrolytic enzymes, and treatment interruption. For diarrhea, recommendations are patient education, loperamide, diphenoxylate, cholestyramine, probiotics, tincture of opium, and antidiarrheal agents, and avoidance of lactose, high roughage, fatty and spicy foods, fruit juice, and caffeine. For hand-foot syndrome, recommendations include use of emollients, wearing gloves, and avoiding constrictive footwear, hot water, urea- or salicylate-containing creams, and treatment interruptions. For fatigue, recommendations include encouraging activity, maintaining normal work and social schedules, providing supportive care, and considering antidepressants, methylphenidate, sleep medication, and treatment-free intervals.

This review adds nothing new to the limited body of evidence in this area, and does not include a huge body of literature related to the management of fatigue and diarrhea symptoms. Most evidence reviewed was of low quality and expert opinion. No process by which the group evaluated the evidence strength in order to make full recommendations is described, and the result is generally a listing of previously documented opinions related to the management of these symptoms.

This review provides recommended assessments and management approaches that are at the level of expert opinion only.

DOI Link: doi: 10.1097/NOR.0000000000000098

To explore effects of music and relaxation interventions on anxiety among patients with cancer and orthopedic interventions

Patients were randomly assigned to the music group, relaxation group or usual care control. Participants in the music group listened to a 20 minute CD of music composed by the hospital’s music therapist. The CD used harp and vocal music with spoken relaxation instructions. Patients in the relaxation group listened to and viewed a music video for 20 minutes that featured nature scenes and instrumental music. The control group were allowed 20 minutes of unstructured free time and were not allowed to listen to music during that time. The intervention was provided once during the first 48 hours of hospital admission. Study data were obtained immediately before and after the intervention.

• N = 112
• MEAN AGE = 60.6 years (range = 24-87 years)
• MALES: 37%, FEMALES:  63%
• KEY DISEASE CHARACTERISTICS: 49% were patients with cancer
• OTHER KEY SAMPLE CHARACTERISTICS: 59% were receiving anti-anxiety medications

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Illinois

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Spielberger State Trait Anxiety scale
• Blood pressure and heart rate

Although there were some differences among groups in single items on the anxiety measurement tool, there were no differences across groups for total anxiety scores. Anxiety scores declined in all on average (p < 0.001)

Results did not show effectiveness of the music and relaxation interventions used here, although anxiety did decline somewhat more in both intervention groups.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: Interventions were delivered via the hospital TV system, so could only be viewed at certain times. There is no description of the reason for hospitalization, so the degree to which some patients may have been in more anxiety-producing situations is unknown. There was no subgroup analysis to account for the potential impact of anti-anxiety drugs administered.

This study did not provide strong evidence supporting effectiveness of music and relaxation interventions for anxiety among the hospitalized patients involved. At the same time, there have been some studies showing benefits of music for various symptoms, and although not significant, this study did show greater reduction in anxiety with the intervention. This type of intervention is low risk and low cost, and may be beneficial to some patients. Here, the intervention was provided via the hospital television system, which can provide a very practical approach to delivery of the intervention.

DOI Link: doi: 10.1055/s-2002-19594

Carbamazepine was tested in the prevention of chemotherapy-induced perihpheral neuropathy (CIPN) in 10 of 40 patients receiving oxaliplatin, folinic acid, and 5-FU chemotherapy. Ten patients also received carbamazapine 200 mg orally. Carbamazepine 200–600 mg was administered orally, with doses adapted to serum levels of 3-6 mg/l starting the week prior to treatment for two days, increased dose to 600 mg orally, and then doses were titrated to meet serum levels of 3-6 mg/l. Carbamazapine was administered until the end of oxaliplatin therapy, but if CIPN symptoms continued, carbamazepine also was continued until symptoms dissipated.

• A total of 40 pretreated patients with advanced colorectal cancer received combination chemotherapy with oxaliplatin 85 mg/m² on days 1, 15, and 29.
• Folic acid 500 mg/m² and 5-FU 2,000 mg/m² were given on days 1, 8, 15, 22, 29, and 36.

The study was a non-randomized pilot design.

• Weekly neurologic examinations measured vibratory sensibility of the plantar surfaces of feet and hands by a tuning fork, cold-induced symptoms, and documentation of side effects.
• Neuropathy also was assessed by the World Health Organization toxicity grading scale.

No WHO grade 2-4 neuropathy was found in the patients treated with carbamazepine compared to 30% who experienced grade 2-4 neuropathy in a historical control group.

• The study's non-randomized, non-blinded design was a limitation, as was the use of a historical comparison group.
• The very small sample size of 10 participants precludes comparison of group differences.
• Study methods and analysis were not well described.

Examine effects of the combination of self hypnosis and pharmacologic pain management

Patients with cancer related pain were randomly assigned to the order in which they received two different approaches: self hypnosis with pain medications and pain medications alone. Patients used a daily log to record pain levels and use of analgesics.

Sample Size: 39

Age Information:  No information reported

Gender: Not reported

Diagnosis Information: Not provided

 

Setting Type: Single site, Outpatient setting

Location: United Kingdom

Long term followup

End of Life and Palliative Care

Single group crossover design – randomized

Visual analogue scale Stanford Hypnotic Clinical Scale for Adults (for response or non-response to self hypnosis)

11 patients reported achieving pain control, 12 reported benefits in relaxation, rest and sleep, and 9 patients reported no impact.

The study report lacks full quantitative findings and thus, very limited information about the efficacy of hypnosis

Small sample 100. No analysis of differences between hypnosis and “control” condition. Those who added self hypnosis first in the crossover sequence were likely to have contaminated results that occurred later in the control condition. No disease related or other demographic information about the sample is provided. Very limited reporting of results and analysis of findings

This study provides little information and no clear support for efficacy of hypnosis for chronic cancer related pain.

DOI Link: doi: 10.1002/ch.348

To examine the effects of the combination of self-hypnosis and pharmacologic pain management

Patients with cancer-related pain were randomly assigned to the order in which they received two different approaches—self-hypnosis with pain medications and pain medications alone. Patients used a daily log to record pain levels and the use of analgesics.

• N = 39
• AGE: No information reported
• MALES, FEMALES: No information reported
• KEY DISEASE CHARACTERISTICS: Not provided

• SITE: Single site
• SETTING TYPE: Outpatient setting
• LOCATION: United Kingdom

• PHASE OF CARE: Long-term follow-up, end-of-life and palliative care

• Single group crossover design
  • Randomized

• Visual analog scale
• Stanford Hypnotic Clinical Scale for Adults (for response or non-response to self-hypnosis)

Eleven patients reported achieving pain control; 12 reported benefits in relaxation, rest, and sleep; and 9 reported no impact.

The study report lacks full quantitative findings and, thus, very limited information about the efficacy of hypnosis.

• Small sample of less than 100
• No analysis of the differences between hypnosis and \"control” condition
• Those who added self-hypnosis first in the crossover sequence were likely to have contaminated results that occurred later in the control condition.
• No disease-related or other demographic information about the sample is provided. 
• Very limited reporting of results and analysis of findings

This study provides little information and no clear support for the efficacy of hypnosis for chronic cancer-related pain.

DOI Link: doi: 10.1111/j.1365-2125.2010.03743.x

To evaluate the effect, toleration, and pharmacokinetics of dose titration of cannabis oral spray added to standard therapy to control chemotherapy-induced nausea and vomiting (CINV) in patients receiving a moderately emetogenic regimen

• Patients were eligible if they had experienced more than 24 hours of CINV despite standard antiemetic treatment after receiving one day of moderately emetogenic chemotherapy (MEC).
• Standard antiemetics included corticosteroids, 5-HT₃ antagonists, or metoclopramide.
• The Cannabis-based medicine (CBM) used was a mixture of tetrahydrocannabinol (THC) and cannabidiol 1:1 (Sativex®), with other cannabinoid derivatives, delivered in an oral spray.
• Patients were randomly assigned to the Cannabis spray (CBM) or a placebo, which was designed to match the appearance, smell, and taste of the active formula.
• On the first day of treatment, subjects received up to 3 sprays within a two-hour period following chemotherapy administration. If no signs of intoxication were seen after the first spray, a second and third were given after 30 minutes and 120 minutes.
• Patients were advised to increase home dose until day four, with up to 8 sprays within any four-hour period, every 24 hours.
• Blood samples were collected at several time points for the pharmacokinetic analysis.

• The study consisted of 16 participants.
• Median age was 50 with a range of range 34–76 years.
• The majority of participants were female (94%).
• Most patients had breast cancer.
• All patients had received one cycle of chemotherapy and were enrolled in the following cycle that included MEC agents. All had good performance status.
• Exclusion criteria were current use of illicit drugs or alcohol abuse, radiation therapy to abdomen or pelvis within one week, or cannabinoid use within 30 days prior to enrollment.

They study was conducted at multiple outpatient settings in Barcelona, Spain.

All patients were in active treatment.

This was a randomized, double-blind, placebo-controlled, parallel, phase-II trial.

Complete response was defined as no vomiting and a mean nausea score of ≤ 10 mm.

Partial response was defined as vomiting 1-4 times daily and a mean nausea score of ≤ 25 mm on a 100-mm visual analogue scale (VAS).

The following additional measurement instruments were used.

• Morrow Assessment of Nausea and Vomiting (MANE) questionnaire for frequency and duration of nausea and vomiting
• Functional Living Index-Emesis (FOIE) patient daily diary for recording of adverse events
• Daily structured telephone interview

• The mean number of daily sprays during the four days after chemotherapy was 4.81 in the CBM group, equivalent to 12.9 mg of THC.
• In the CBM group, 6 out of 7 patients tolerated dose titration. One patient discontinued treatment because of anxiety, somnolence, visual hallucinations, and confusion. These symptoms disappeared after three hours.
• Somnolence, dry mouth, and fatigue were the most common adverse events in both groups.
• In the delayed period, complete response was higher in the CBM group (71.4%) than in the placebo group (22.2%).
• In the acute period, no difference was found between the groups.
• A larger percentage of patients in the CBM group had no delayed emesis (71.4%) or nausea (57.1%) than in the placebo group (22.2%).
• Plasma concentrations showed a wide variability across subjects and suggested that patients following a repeat-administration schedule accumulate CBM active compound over time, despite the relatively short half-life of the active compounds.

The addition of this formulation of Cannabis to standard antiemetic treatment appears to improve control of delayed nausea and vomiting with MEC.

• The sample size was extremely small.
• The standard antiemetic regimen was less than what is currently recommended; however, it did follow recommendations at the time of the study.
• No discussion of the use of or need for rescue medications was provided.

• Other research has shown effectiveness of Cannabis compounds for CINV.
• The addition of Cannabis compounds to other antiemetic regimens may be specifically helpful in patients with refractory CINV, and it may be most helpful with delayed nausea and vomiting.
• The delivery system of an oral spray provides an alternative that may be helpful. Further research in the use of this formulation is warranted.

DOI Link: doi: 10.1093/annonc/mdr045

The aim of the study was to evaluate the efficacy of venlafaxine for the prevention and treatment of oxaliplatin-induced peripheral neuropathy.

Patients who reported distressing acute neurotoxicity after oxaliplatin-based chemotherapy were randomly assigned to receive either placebo or venlafaxine hydrochloride 50 mg one hour prior to chemotherapy infusion and venlafaxine extended release 37.5 mg twice daily from day 2 to day 11. Placebo was given with the same timing. From day 12 on, no venlafaxine extended release was given. Study treatment continued as long as the oxaliplatin treatment lasted. Study evaluation and data collection was conducted pretreatment, daily on day 1 through 5 of chemotherapy treatment, and at three months after study completion.

• A total of 42 patients were studied (21 women, 21 men)
• The median age was 67.4 years with a range of 32–84.4 years.
• Patients had multiple tumor types,
• Most patients were receiving FOLFOX. The median number of cycles at study inclusion was 4.5.

The study was conducted at a single outpatient setting in France.

Phase of care

• Active antitumor treatment

The study had a double blind, placebo-controlled, randomized trial design.

• Neuropathic pain symptom inventory
• Numeric rating scale for functional impairment
   

The proportion of patients reporting full relief of acute neurotoxic symptoms was 31.3% compared to 5.3% in the placebo group (p = 0.03).  In the venlafaxine group, 68.8% reported more than 50% symptom relief compared to 26.3% on placebo (p = 0.02). There were no grade 3 or 4 adverse events related to venlafaxine. Among those receiving venlafaxine, the most common adverse events were nausea and vomiting, asthenia, orthostatic hypotension, and somnolence. These side effects occurred more frequently in the venlafaxine group (p < 0.03).

The findings suggest that venlafaxine as studied here is effective in reducing acute neurotoxic symptoms associated with oxiplatin chemotherapy.

A small sample size (less than 100 participants)

The findings provide support for the efficacy of venlafaxine to prevent acute oxiplatin-related neurotoxicity. The study is limited by sample size, so the results are inconclusive. Additional research in this area is warranted.