• Patients were instructed to swish around crushed ice cubes in their oral cavity from 5 minutes before until 30 minutes after IV administration of 5-fluorouracil (5-FU).
• Physician evaluators were blinded.
• Patients received five consecutive days of leucovorin (20 mg/m² per day) plus 5-FU (600 mg/m² per day) administered over a few minutes (Mayo regimen).
• Patients were evaluated for three consecutive cycles.

• The cryotherapy group consisted of 36 patients. Mean age was 62.6 years, with a range of 50–82 years. 
• The control group consisted of 40 patients. Mean age was 61 years, with a range of 42–78 years.
• Patients with head and neck cancer were excluded.
• Nine patients were unwilling to join the cryotherapy group because of tolerance to oral ice.

• Patients were instructed to complete a questionnaire one month after cryotherapy prior to the following course.
• Two blinded otorhinolaryngologists graded patients on a 0–4 scale.

• The percentage of patients free from oral toxicity was significantly higher in the cryotherapy arm (p < 0.01) based on physician evaluations.
• The percentage of patients not suffering from mucositis was significantly higher in the cryotherapy arm following the first and third cycles (p < 0.05) but also after the second chemotherapy cycle (p < 0.01).

• Researchers were unable to double blind cryotherapy.
• The sample size was small.
• Results depended on assessment at completion of cycles, so some changes may have been missed. This study would have benefited from having additional, earlier assessment times.

Assess efficacy of gabapentin in controlling hot flashes in women with breast cancer

Patients were randomized to placebo, gabapentin 300 mg/day, or gabapentin 300 mg three times a day for eight weeks.

• Women with breast cancer having an average of two or more hot flashes per day (N = 420).
• Evaluable data for 371 patients at four weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at eight weeks (113 placebo, 114 gabapentin 300 mg, 120 gabapentin 900 mg).
• Mean age: 55 years old
• Inclusion: Adult women with history of breast cancer and were having an average of two or more hot flashes per day; adjuvant tamoxifen use was permitted
• Exclusion: Currently receiving chemotherapy; use of venlafaxine, clonidine, or anticonvulsants not permitted; pregnancy, breastfeeding, use of steroidal contraception, coronary insufficiency, recent history of myocardial infarction, symptomatic cardiac disease, peripheral or cerebrovascular disease, stroke, syncope, or symptomatic hypotension; hepatic dysfunction (aspartate aminotransferase concentration above twice the upper limit of normal or bilirubin concentration above the upper limit of normal), renal dysfunction (serum creatinine concentration above 1–25 times the upper limit of normal); allergy to gabapentin

University community clinic oncology program

Randomized, double-blind, placebo-controlled multi-institutional trial.

• Hot flash diary one week prior to study and during weeks 4 and 8 of treatment
• Symptom inventory pretreatment, weeks 4 and 8 of treatment.

Decreases in hot flash severity scores between baseline and weeks 4 and 8, respectively were: 21% and 15% in the placebo group; 33% and 31% in the group assigned gabapentin 300 mg; and 49% and 46% in the group assigned gabapentin 900 mg. The differences between the groups were significant (p = 0.0001 at four weeks and p = 0.007 at eight weeks by analysis of covariance for overall treatment effect).

Gabapentin was effective in control of hot flashes at a dose of 900 mg/day but not at a dose of 300 mg/day.

• Long-term use of gabapentin not assessed 
• Withdrawal rate of 12% at four weeks and 17% at eight weeks

The study evaluated oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes.

Participants received oral clonidine hydrochloride 0.1 mg daily or placebo at bedtime for eight weeks.

The study enrolled 198 postmenopausal women (mean age 71 years) with breast cancer taking tamoxifen and stratified by time since menopause (less than three years, more than three years), duration of tamoxifen use (less than one year; longer than one year), and baseline frequency of hot flashes (less than 10 per day, more than 10 per/day). One hundred forty-nine (149) completed the study. Of the participants, 99 received clonidine and 99 received the placebo.

• Inclusion criteria:
  • Postmenopausal women who had been receiving adjuvant tamoxifen therapy for breast cancer for at least one month and reported at least one hot flash per day
  • Normal hepatic and renal function
• Exclusion criteria:
  • Premenopausal women 
  • Women receiving concurrent chemotherapy or endocrine therapy for breast cancer, hypertension therapy or concurrent treatment with monoamine oxidase inhibitors; L-dopa, piribedil, tricyclic antidepressants, or sedatives
  • Coronary insufficiency, recent history of myocardial infarction (within three months), symptomatic cardiac disease, peripheral or cerebrovascular disease, syncope, or symptomatic hypotension
  • Allergy or adverse reaction to clonidine

A community oncology clinic conducted the study.

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

Measures included:

• Daily hot flash diary for one week at baseline, during the weeks 4 and 8 during treatment, and four weeks after the end of treatment
• Symptom checklist

One hundred forty-nine (149) of 198 completed 12 weeks of follow-up (73 in clonidine group and 76 in placebo group.) Oral clonidine was shown to be effective. The mean decrease in hot flash frequency was greater in the clonidine group after week 4 (37% to 20%) and week 8 (38% to 24%). The clonidine group had more difficulty with sleep (41%–21%). A significant difference was seen in the mean change in QOL scale (p = 0.02) at 8 weeks.

Limitations included:

• Evaluation for eight weeks
• No evaluation of long-term effectiveness

To prepare and evaluate an allopurinol mouth rinse for prophylaxis of fluorouracil-induced mucositis  

Allopurinol mouthwash (1 mg/ml) or placebo was administered 1, 2, and 3 hours after chemotherapy and three consecutive nights for 30 seconds. Patients were instructed to neither wash their mouths nor to eat and drink for 15 minutes afterward.

• The study reported on 30 patients, with a mean age of 56.9 years (SD = 10.3 years) for the allopurinol group and 49.5 years (SD = 13.8 years) for the placebo group.
• The percentage of males was not mentioned in the study. The allopurinol group was 60% female and the placebo group was 66.7% female.
• Cancer diagnoses were breast (n = 13), colon (n = 12), rectum (n = 2), gastric (n = 3), pancreas (n = 2), and esophageal (n = 1).
• All patients with malignant disorders, who were going to receive 5-FU-containing chemotherapy in the outpatient setting, were analyzed.

This was a single-site, outpatient study conducted in a clinic in Sari, Iran.

• All patients were undergoing the active treatment phase of care.
• The study has clinical applicability for end of life and palliative care, elderly care, late effects and survivorship.

This was a placebo-controlled, double-blinded, randomized clinical trial.

An independent physician completed questionnaires consisting of demographic parameters, medical status, quality-of-life survey, and mucosal injury scoring table (based on World Health Organization [WHO] scales for mucositis).

• In the allopurinol arm, 11 of 15 patients (73.3%) did not have mucositis, four (26.6%) had grade 1 (mild), and none had mucositis at a higher grade.
• In the placebo arm, 8 of 15 patients (53.3%) showed no mucositis, five (33.3%) had grade 1, and two (13.3%) developed grade 2 mucositis.

No significant differences were found between the groups with regard to occurrence and severity of mucositis.

• The sample size was small with fewer than 30 patients.
• The time period for treatment and follow up was very short.
• The rationale for timing of the intervention was not  clear.
• Substantial differences existed between groups in the type of chemotherapy given, which would be likely to affect mucositis development.
• No information was provided regarding patient compliance with the protocol for oral rinsing.
• The study was not blinded.

Because of compliance issues with the mouth rinse regimen, low concentration of the allopurinol in the rinse, and a small sample size, the treatment was deemed ineffective in prevention and severity of mucositis. Further studies are needed once the limitations are removed.

To evaluate the effects of ginger on acute and delayed chemotherapy-induced nausea and vomiting (CINV) in women being treated for breast cancer

Consecutive patients were alternatively assigned to the treatment or control group. Those in the treatment group were given 1.5 g ginger per day in addition to a standard antimetic regimen. The standard regimen consisted of graniestron plus dexamethasone. Treatment was given for four days.

• The study consisted of 78 patients.
• The mean age of patients was not reported.
• All of the patients were female.
• All of the patients had been diagnosed with  breast cancer; the majority were receiving docetaxel, epirubicin, and cyclophosphamide.

The study was conducted at a single site in Iran.

All patients were in active antitumor treatment.

This was a randomized, open-label comparison.

The Rhodes index of nausea, vomiting, and retching was used to measure CINV.

The authors reported that patients in the treatment group had significantly less nausea in the first six hours of the study; however, no differences were found between groups at any other time point, and no differences were found between groups in terms of vomiting.

No significant differences were found between groups in CINV other than less nausea in the first six hours after chemotherapy with ginger.

• The sample size was small with fewer than 100 participants.
• A risk of bias exists because no blinding or random assignment was used.
• The measurement methods were not well described. The timing and exact use of CINV measurement was not described. 
• The randomization of group assignment was questionable.
• No demographic information was reported. Evaluation of demographic differences between the groups, which could have influenced CINV, was not included.
• The authors suggested that ginger had positive effects, despite the lack of major significant findings, suggesting study bias. 
• The study period was short.
• Patient experience with previous chemotherapy courses or prior CINV was not reported.

These findings did not provide strong support for the efficacy of ginger in the management or prevention of acute or delayed CINV in patients receiving moderately emetogenic chemotherapy.

• FINAL NUMBER STUDIES INCLUDED = 8
• TOTAL PATIENTS INCLUDED IN REVIEW = 950
• SAMPLE RANGE ACROSS STUDIES: 14–134 patients
• KEY SAMPLE CHARACTERISTICS: All received surgery; studies were done at various phases of care

PHASE OF CARE: Multiple phases of care

Studies included those with combined exercise and massage, support and massage for lymphedema, reflexology, foot massage, and aquatherapy. Eight randomized, controlled trials (RCTs) assessed effects on anxiety, and a meta-analysis showed no significant effect of massage on anxiety. Three RCTs looked at effects on fatigue, and a meta-analysis showed improvements in fatigue (SMD = -0.61, p = 0.01). Four RCTs looked at pain, and a meta-analysis showed improvement in pain (SMD = -0.33, p = 0.07, 95% CI -0.69,-0.03).

The evidence from this meta-analysis suggested that massage interventions may be beneficial in the management of fatigue and pain for women with breast cancer. The results did not suggest effectiveness for anxiety.

The specific effects of massage alone were difficult to identify because most studies included other interventions along with massage. The types of massages used were different, and there was no accommodation for the use of medications. There was high heterogeneity among the studies that examined effects on fatigue. The studies included had multiple methodologic flaws. Several studies were counted twice or more in the meta-analysis. Although different outcomes were reported, it was clear from the data that the study sample was the same in different publications.

Massage is a low-risk intervention that may be beneficial in combating fatigue among patients with cancer. This analysis provided evidence in support of massage; however, this was particularly strong given the study design flaws, the variability in types of massage, and the other interventions that were included in the analysis at various phases of cancer care. Additional well-designed research on massage would be helpful to clarify clinical applicability.

To determine if a decrease in the amount of anesthesia and a decrease in recovery time would occur in either of the treatment groups receiving music therapy compared to the usual care or control group.

Patients who met inclusion criteria were randomly assigned to a five-minute intervention or usual care in one of three groups: patient-selected live music (LM) with therapist-selected recorded music during the operative procedure; patient-selected recorded music (RM) preoperatively with therapist-selected recorded music during the operative procedure; or usual care (UC) preoperatively with noise-blocking earmuffs during the surgical procedure.

• N = 207 (LM = 69, RM = 70, UC = 68) 
• AGE: Range = 18-94 years
• FEMALES:  100 %
• KEY DISEASE CHARACTERISTICS: Breast cancer or suspected breast cancer biopsy, lumpectomy, and re-excision
• OTHER KEY SAMPLE CHARACTERISTICS: English-speaking women undergoing known or suspected breast cancer surgery; aged 18-years or older; ASA classification I–III; all were given fentanyl 1 mcg/kg and versed 0.02 mg/kg followed by adherence of a monitor sensor to the forehead and a propofol drip. 

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: University Hospitals Case Medical Center in Cleveland, OH; University Hospitals Richmond Medical Center in Richmond Heights, OH

• PHASE OF CARE: Diagnostic

• Randomized, controlled trial using three groups

• Global Anxiety-Visual Analog Scale (GA-VAS): before and after the five-minute music intervention or control condition
• Bispectral Index (BIS) monitor sensor: an intraoperative measure of sedative effects on the brain corresponding to alertness (goal of BIS 70 was target for recording amount of propofol administered)
• Recovery time: the interval between the end of surgery and the time the recovery nurse determined that d/c criteria was met
• Patient satisfaction: five-item questionnaire administered before discharge with questions based on the CAHPS Surgical Care Survey of the Consumer Assessment of Health Providers and Systems (CHAPS) program

No significant baseline differences in the three groups nor in amount of propofol used to achieve sedation level of BIS 70. Intervention groups showed significantly decreased levels of anxiety compared to control group; no significant difference in changes between the two groups were noted. Greater changes in anxiety level were seen when baseline anxiety scores were high: (i.e., the higher the pretreatment anxiety, the greater the change [reduced anxiety] in anxiety level after treatment). The amount of change (slope) in the LM group and RM groups were not different from each other, but were different from the amount of change (slope) in the control group. Recovery time, or time to discharge readiness determined by the recovery nurse, was not different for the intervention groups compared to the control group, but was shorter in the LM group compared to the RM group. Patient satisfaction scores revealed no differences among the three groups.

Noise-blocking earmuffs and music therapy were not found to reduce the amount of anesthesia required as measured by the BIS monitor. Satisfaction scores were high with and without music therapy. Music therapy was found to reduce anxiety more when initial anxiety scores were high.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: Blinding was not possible in busy preoperative or operative setting. Completing a questionnaire about anxiety may stimulate anxious thoughts. There were no attentional control as usual care in preoperative setting involves caring personnel. The BIS monitor may not provide the sensitivity for measuring changes based on music therapy in these types of patients undergoing these types of operative procedures.

Patients felt cared for and cared about with or without music therapy; anxiety levels were lowered with either type of music therapy when baseline anxiety levels scored high. Nurses may conduct anxiety screening and offer music therapy to reduce anxiety scores as part of the usual care environment.

To evaluate the efficacy of acupuncture for the relief of cancer-related pain in adults

Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Allied and Complementary Medicine Database (AMED), SPORTDiscus, and PsycINFO.

Search keywords included acupuncture therapy, Medicine East Asian traditional, acupressure or acupoint*, traditional Chinese medicine, pain, neoplasm or cancer. All databases were searched from their inception to October 2010. Authors provided an extensive list of search terms and the strategy per database. In addition, to identify further references for analysis, investigators searched the reference lists of eligible studies as well as lists associated with previous systematic reviews.

Studies were included if they

• Were randomized controlled trials (RCTs).
• Evaluated any type of invasive acupuncture. (Both Western-style and traditional Chinese acupuncture were included in the search.)
• Involved patients who had cancer-related pain as defined by commonly used rating scales or questionnaires.
• Involved patients 18 years of age or older.

Studies were excluded if they were not RCTs or if they involved pain due to preexisting noncancer pathology or treatments (e.g., chemotherapy), neuropathic pain, or procedures such as surgery.

The initial search retrieved 253 articles. Of these, only three RCTs were appropriate for inclusion. None provided extractable data for meta-analysis. Investigators evaluated study quality by using the Jadad scale. Two of the three studies had low-quality scores (2 points out of 5).

The three studies included a total of 204 patients. Across studies, sample size range was 48–90. Authors reported no other sample characteristics.

• One study compared the effects of auricular acupuncture at acknowledged acupuncture points to acupuncture at placebo points. Compared to the placebo group, the acupuncture group reported a significant decrease in pain intensity (p < 0.0001), compared to baseline, at two months.
• One study concluded that the analgesic effect of acupuncture was greater than that of medication (p < 0.05). However, in this study researchers set a predetermined level of pain as the criterion for general effectiveness; researchers did not analyze actual pain data. The study did not report raw data or standard deviations.
• One study reported that long-term effects were similar in groups treated with acupuncture and medication. The study provided no explanation regarding pain measurement.
• The evidence from only one high-quality RCT was insufficient to provide the basis for a judgment about the efficacy of acupuncture. This study involved apparent inconsistencies in reporting and some inadequate acupuncture doses.

This study provided insufficient evidence to determine the effectiveness of acupuncture for the relief of cancer-related pain.

Available evidence is inconclusive or of low quality.

Acupuncture is being more widely used to treat cancer-related pain, but evidence is insufficient to support the effectiveness of this treatment. More well-designed studies of acupuncture are needed, and study designers should ensure adequate sample sizes, homogeneity of cancer pain conditions under study, consistent dosing of acupuncture, valid controls, and reliable pain outcomes measurement. The authors point out that guidelines for the use of acupuncture are available. They suggest that practitioners use such guidelines and remain aware of the limitations of acupuncture.

STUDY PURPOSE: To evaluate acupuncture for relief of cancer-related pain in adults with updated evidence

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED: Five studies, three from a prior systematic review
• TOTAL PATIENTS INCLUDED IN REVIEW: 285 
• SAMPLE RANGE ACROSS STUDIES: 21–90 patients

PHASE OF CARE: Not specified or not applicable

There was insufficient evidence to draw firm conclusions.

There is insufficient high-quality evidence in the area of acupuncture for cancer-related pain.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Low sample sizes

There is a current lack of evidence to appropriately evaluate the efficacy of any type of acupuncture for management of cancer-related pain.

To compare the effects of paroxetine to placebo on sleep problems in patients with cancer.

This study was a post hoc analysis of data from a randomized, controlled trial (RCT) previously implemented to examine the effects of paroxetine on fatigue. Patients seen between 1997 and 1999 with any type of cancer receiving chemotherapy were recruited and randomized to either 20 mg of paroxetine daily or placebo. Data were collected seven days after each chemotherapy cycle. Patients received follow-up and reminder telephone calls from the study nurse. For analysis purposes, patients were classified as those with sleep problems or good sleepers based on depression inventory scores. Those who reported sleep difficulties of any type at least one to two nights a week were classified as having sleep problems. Responses to single items regarding sleep on rating scales used in the study were used as primary outcome measures.

• The sample was comprised of 426 patients (23.9% male, 66.1% female).
• Mean age was 56.4 years.
• Multiple tumor types were included; the highest volumes were breast, lung, and hematologic cancers.
• Of the patients, 72% were married.
• At baseline, 80.8% of patients had sleep problems as defined in the study.

• Single site 
• Outpatient 
• University of Rochester

Patients were undergoing the active antitumor treatment phase of care.

The study was a secondary analysis of a double-blind, placebo-controlled RCT.

• Hamilton Depression Inventory (HDI)
• Hamilton Depression Rating Scale (HDRS)
• Center for Epidemiologic Studies Depression Scale (CESD)

At the end of cycle 4 of chemotherapy, there was a significant difference in the prevalence of patients with sleep problems between those on paroxetine (79.3%) versus placebo (88%) (p = 0.01; d = 0.23). Rates of severity of sleep problems were not significantly different between the groups.

The findings provide relatively weak evidence that paroxetine may help patients with cancer undergoing treatment to reduce the prevalence of mild sleep problems. Validated sleep quality measures were not used.

• Unintended interventions or applicable interventions not described would influence the results.
• Measurement validity/reliability was questionable.
• No other relevant interventions, or lack of these that could impact sleep, were described. 
• The method of measurement of sleep disturbance is questionable; selected items within depression scales were used, rather than validated measures designed to measure sleep. 
• The criterion for the definition of sleep problems sets a very low standard to represent sleep problems.

Further research on the effects of selective serotonin reuptake inhibitors (SSRIs) to improve sleep in patients with cancer who have sleep problems is needed. The positive findings are limited by the measurement of sleep problems and the fact that this analysis was performed from a study that was not designed to measure the outcome of sleep.