GMCSF subcutaneously
(4 mcg/kg) from days 6-10 during cycle following the cycle Grade ≥ 2 mucositis was reported.

Also received “standard” anti-mucositis treatment

The study was comprised of 31 patients, age 39-77 years with a median age of 68.
Three stage phase II trial
Colorectal cancer treated with 5FU plus leucovorin and reporting mucositis ≥ Grade 2.
 

Chen design
WHO Mucositis – 3x/wk:

Grade 0 = none

I = painless ulcers, erythema, or mild soreness
2 = painful erythema, edema, or ulcers
3 = can’t eat solids
4 = TPN or enteral support
 

77 GM-CSF cycles were administered (median/pt = 3).

Success claimed based on reduction of at least one grade of mucositis.

9 of 20 responders mucositis disappeared – 64.5%

45% with mucositis responded, 12.9% failure, 3.2% stopped treatment
3.2 % (1 patient) with mucositis plus diarrhea responded, 3.2% treatment failure, 3.2% stopped treatment

Toxicity in 7 of 20 patients

 

Claim results are rationale for well-designed trial

No control group
Small N
No P values stated percentages hard to follow.

To evaluate the effectiveness of gabapentin for cancer-related neuropathic pain

Gabapentin was administered at a dose of 300 mg/day up to 1.8 g/day over 15 days. Final doses were taken in three divided doses. Two parallel groups were recruited with either treatment-related (n = 25) or tumor-related (n = 37) neuropathic pain. Gabapentin was dose-escalated from 300 mg/day to 1.8 g/day. Median dose was 1,200 mg/day. Patient selection was nonrandomized.

• The study reported on 62 patients: 16 males and 46 females, 21 of whom had had breast cancer.
• A total of 41 patients completed to day 15.
• Patients were excluded from the study if they had started treatment that was likely to affect their neuropathic pain, such as anticonvulsants (< one month), antidepressants or steroids (< seven days), and anesthetic interventions, such as nerve blocks (< two weeks).

Patients were selected from inpatient and outpatient settings in a U.K. tertiary referral center.

Prospective, open-label studies of inpatients and outpatients

Patients completed pain and side-effect scores and were evaluated by a clinician on days 0, 8, and 15. In addition, pain scores were obtained on day 4. Pain was assessed using the modified Brief Pain Inventory (BPI) to measure pain on a 0–10 scale. Patient descriptors of pain and scores of activities of daily living (0–10 scale) were collated together with demographic data. Toxicity scores ranged from “not at all” to “a little,” “quite a bit,” or “very much.”

Baseline and final pain scores were not significantly different between the tumor-related and treatment-related groups. In addition, ANOVA did not show etiology to be a significant predictor of response to gabapentin. Data from both groups were pooled into the primary analysis. A total of 41 patients completed the study, with the median-range dose of gabapentin to be 1,200 mg/day. A total of 28 of 62 patients achieved at least a one-third reduction in their pain score (95% CI); the number needed to treat to obtain this benefit was 2.2. There was a significant reduction in all scores measuring the impact of pain on daily living (p < 0.003). ANOVA suggested that gender and cancer diagnosis, but not etiology of neuropathic pain or type of neuropathic pain, were independent predictors of change in average pain score. There was suggestion that beneficial effect was only in women, not men; men with bowel or lung cancer showed no benefit. This may be a chance subgroup finding. There was significant reduction in worst, average, and current pain scores (p < 0.002), but not in least pain scores. The tumor group described pain as shooting, pins and needles, and the treatment group described pain as hot, burning sensations. There was no significant difference in pain scores on day 8 compared to day 15. No further pain relief was reported from day 8 to day 15—if improvement is not seen in one week, this suggests that an alternative drug should be started. Six patients (10%) discontinued study because of probable drug-related side effects, 14% reported mild/moderate side effects, and 45% were already taking steroids or antidepressants, although doses did not change during the study.

Gabapentin is an effective treatment for cancer-related neuropathic pain from both tumor and treatment.

• The study time period was short and therefore may not have given enough time for patients to gain confidence and reduce the amount of opioid use. Further, patients were not randomized, so the placebo effect is not clear.
• Breakthrough medications were available, but their use was not documented.
• Women had a better response, which may be a chance subgroup finding or related to diagnosis (21 of 46 female patients had breast cancer).
• Gabapentin was not used prophylactically.
• Dose escalation was limited by side effects. Side effects were not clear; 10% left study due to side effects, and 14% had mild/moderate side effects.
• Of 62 patients, 41 completed study to day 15.
• Patients in the tumor group were more likely to be on steroids, and patients in the treatment group were more likely to be on antidepressants.
• This was a single-site study; there was no comparison between methods employed at different radiation centers.

Side effects included drowsiness, unsteadiness, dizziness, nausea, headache, and others. There was no change in opioids during study—one might question whether there could there be a synergistic effect between gabapentin and opioids. Studies need to be performed to determine if the escalation of a dose greater than 1,800 mg/day is beneficial between men and women and different cancer diagnoses.

To compare the efficacy of two dose levels of octreotide long-acting release (LAR) in preventing chemotherapy-induced diarrhea (CID) in patients with active or prior CID

A sample of 124 evaluable patients were assigned randomly to either the 30-mg or 40-mg octreotide dose group. The first dose of ocreotide was given intramuscularly 7–14 days prior to day 1 of the patient's next chemotherapy cycle. The second dose coincided with the chemotherapy cycle. Subsequent cycles were given every 28 days up to a total of 6 doses on a schedule independent of the chemotherapy cycles. Prior to initiation of octreotide LAR, patients were given a 100-mcg test dose of octreotide subcutaneously to determine potential intolerance.

• The two treatment groups were similar in current chemotherapy regimens, severity of most recent diarrhea episode, body weight, primary tumor type, and proportion of patients with colostomy prior to study entry.
• More than half (57%) of patients were receiving regimens with 5-fluorouracil (5-FU) with or without irinotecan, leucovoran, or oxaliplatin; 25% were receiving irinotecan regimens with or without 5-FU, leucovoran, or oxaliplatin.
• Primary tumor types were colorectal (75%), breast (7%), lung (6%), hematologic (1%), other (10%).

This was an open label, randomized, multicenter study with a parallel-group design.

• Patient diaries were collected on a monthly basis to obtain data for diarrhea assessment, concomitant medications, adverse events, and use of healthcare resources.
• Health-related quality of life (QOL) was assessed at baseline and at the end of each study visit using a modified Functional Assessment of Chronic Illness Therapy-Diarrhea (FACIT_D) scale.
• Investigators collected data from the Treatment Satisfaction Questionnare for Medication for Chemotherapy Induced Diarrhea (TSQM-CID), a version of the previously validated TSQM, at baseline for loperamide and diphenoxylate and at the end of study visit for octreotide LAR.
• The primary study endpoint was the proportion of patients experiencing severe diarrhea (National Cancer Institute [NCI] grade 3 or 4).
• Secondary study endpoints were the proportion of patients requiring IV fluids, unscheduled provider visits, and changes in primary therapy because of diarrhea as well as treatment satisfaction and QOL.

• The proportion of patients who experienced severe diarrhea (grade 3 or 4) during the study was 61.7% in the 30-mg group and 48.4% in the 40-mg group (p = 0.14).
• Fewer patients in the 40-mg group experienced severe diarrhea, required IV fluid (p = 0.11), or had unscheduled diarrhea-related healthcare visits (p = 0.11).
• The percentage of patients in the 30-mg group who had changes in their primary therapy as a result of diarrhea was 61.7%, and the percentage in the 40-mg group was 64.1% (p = 0.78).

• No comparison was made between daily and three times per day octreotide and octreotide LAR.
• The 30-mg group contained a significantly greater proportion of females because sensitivity analysis showed no need to adjust for gender.

No specific recommendations regarding the superiority of 30 mg or 40 mg octreotide in the management of CID can be made based on this study.

To evaluate the effects of yoga, massage, and Reiki therapies on stress, pain, anxiety, mood, overall health, and quality of life (QOL)

Data were collected from patients who self-enrolled in yoga, Reiki, and massage services during a six-month period. Patients completed study questionnaires before and after participating in one of these services, within one to three minutes before and after participation.

• N = 150   
• AGE = Not provided
• MALES: 9%, FEMALES: 91%
• CURRENT TREATMENT: Chemotherapy, radiation therapy, other
• KEY DISEASE CHARACTERISTICS: Patients involved were at varied points in the care trajectory, and 75% were either newly diagnosed or had completed initial treatment. Disease types were not reported.

• SITE: Single site   
• SETTING TYPE: Other    
• LOCATION: Community center in Illinois

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

• Quasi-experimental

• 10-point rating scales for all outcome measures

The time patients had been participating in the service ranges from one month to more than three years. Significant changes in pain levels pre- and postservice provision were reported (p < 0.001). Individuals receiving Reiki had higher preservice pain levels. Center staff encouraged patients with pain to enroll in Reiki. No significant postservice differences in pain across the intervention types were reported. All patients reported lower anxiety scores after receiving the service (p < 0.001) with no differences between groups.

Integrative therapies such as Reiki, massage, and yoga may be helpful for management of symptoms such as pain and anxiety.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Author states that this was a repeated measures design and used repeated measures ANOVA, but description of methods looks as if each patient completed study assessment only immediately pre and post a single service. 
• Measurements were at a time point immediately before and after a service—it is unclear how meaningful this timing is in terms of looking at ongoing symptom management.
• Validity of the instrument for measurement and interpretation of anxiety and mood is questionable.
• Pain levels overall were low,suggesting potential floor effects in measurement in non-Reiki patients.
• No information is provided about chronicity, type, etc., for pain, or any other interventions being used for pain.

This study has numerous limitations and high risk of bias, so no firm conclusions can be drawn about the actual efficacy of the interventions being evaluated.

Palifermin was administered at 40 mcg/kg IV for three consecutive days before each of two chemotherapy cycles with fluorouracil (5-FU) or leucovorin (LV).

The study reported on patients with metastatic colorectal cancer receiving 5-FU or LV. The group receiving palifermin had 28 patients, and the group receiving placebo had 36 patients.

This was a phase I and II randomized double-blind, placebo-controlled study.

• The World Health Organization (WHO) Oral Toxicity scale was used.
• Patients were assessed on days 1, 4, 8,12, 15, and at the end of both cycles on day 28.
• Patients also were assessed with the Oral Mucositis Daily Questionnaire, which consists of 10 questions on overall health, mouth and throat soreness, and diarrhea.
• Incidence and severity of mucositis and diarrhea were recorded.

• Statistically significant differences in grade 2 or higher mucositis were observed during the first cycle (p = 0.002).
• Lower incidence of mucositis was observed during the second cycle (still statistically significant for palifermin group) (p = 0.003).
• Fewer patients receiving palifermin required a chemotherapy dose reduction of 10% or more.
• Disease outcomes were similar for the two groups; the authors concluded that palifermin had no effect on the disease in this clinical setting.

• A researcher had relationships with Amgen.
• The study involved the IV formulation.
• Expense was not addressed.
• Palifermin currently is not U.S. Food and Drug Administration (FDA) approved for nonhematologic malignancies.

To evaluate whether cognitive behavioral therapy for insomnia (CBT-I) in combination with a wakefulness-promoting agent, armodafinil, results in better insomnia outcomes in cancer survivors compared to CBTI-I alone

• N = 73  
• MEAN AGE = 56 years
• MALES: 12.5%, FEMALES: 87.5%
• KEY DISEASE CHARACTERISTICS: Self-reported insomnia for at least three months that was caused or worsened by any cancer and its treatment; chemotherapy or radiation therapy completed greater than one month prior and no measurable disease; no sleep aids one week before baseline and throughout 11-week study
• OTHER KEY SAMPLE CHARACTERISTICS: 68% breast cancer; original protocol called for only breast cancer but was broadened to include any cancers

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
• LOCATION: Two northeastern cities in the United States

• PHASE OF CARE: Late effects, survivorship

Randomized, placebo-controlled trial

• Insomnia Severity Index (ISI)
• Pittsburgh Sleep Quality Index (PSQI)
• Demographics, clinical information, and sleep history

Analyses controlling for baseline differences showed that both the CBT-I plus armodafinil (p = 0.001) and CBT-I plus placebo (p = 0.010) groups experienced significantly greater reductions in insomnia severity postintervention than the placebo group with effect sizes of 1.31 and 1.02, respectively. Similar improvements were seen for sleep quality. Gains on both measures persisted three months later. CBT-I plus armodafinil was not significantly different from CBT-I plus a placebo (p = 0.421), and armodafinil alone was not significantly different from a placebo alone (p = 0.584).

• Small sample (< 100)
• Baseline sample/group differences of import
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Patients were told of their random assignment to CBT-I (or another group) after the completion of the two-week baseline period. All study personnel and patients were blinded to medications (armodafinil or the placebo) but not to CBT-I assignment.

Considering the prevalence of insomnia in patients with cancer and survivors, the potential for poorer outcomes if insomnia remains untreated, and the efficacy of CBT-I in treating chronic insomnia, it is desirable that providers and patients obtain increased access to evidence-based nonpharmacologic sleep interventions as an integral part of comprehensive cancer care. The findings of this study demonstrated that the addition of armodafinil to CBT-I treatment did not improve results for sleep.

The intervention involved polarity therapy for a 60- to 70-minute session. A trained therapist used anatomical hand positions (connectors) to examine energy flow, discover trigger points, and restore homeostatic energy flow. Polarity therapy promotes healing, relaxation, and well-being by unblocking and balancing energy flow and reestablishing homeostasis within the human energy field.

• The sample included 15 women older than 18 years in the third week of radiotherapy for breast cancer with a fatigue level greater than 2.
• Average age was 52.5 years (range 35–72).
• Fourteen of 15 patients were Caucasian.

Single radiotherapy center

Patients were undergoing the active treatment phase of care.

This was a pilot study with three arms:

• Arm 1:  standard care
• Arm 2:  one polarity therapy treatment
• Arm 3:  two polarity therapy treatments one week apart.

• Brief Fatigue Inventory (BFI)
• Functional Assessment of Cancer Therapy–Fatigue (FACIT-F)

A statistically significant improvement was observed in fatigue and health-related quality of life in 10 patients who received polarity therapy versus five who did not. There may have been a dose effect. Eight of 10 patients reported improvement.

• The study had a very small sample.
• Certification was required.

Patients were given oral paroxetine 20 mg daily beginning seven days after the initiation of the first cycle of chemotherapy for newly diagnosed breast cancer and continued until seven days following their fourth cycle of chemotherapy or placebo. Randomization was stratified by type of chemotherapy regimen to achieve a balanced design.

• The sample was comprised of 94 women with breast cancer initiating at least four cycles of chemotherapy for breast cancer.
• Mean age was 51.2 years (range 31–79). 
• Of the patients, 89% were Caucasian, 28% were significantly depressed at baseline, and 5% had a hemoglobin less than 11 g/dL.
• There were no significant differences between the intervention and placebo control groups in age, mean baseline measures of fatigue, depression, or general health status.
• The difference in baseline hemoglobin between the intervention group (12.3 g/dL) and the placebo control group (12.9 g/dL) was statistically significant (p < 0.05).

Patients were recruited from a university medical center and two of its affiliated hospitals.

Patients were undergoing the active treatment phase of care.

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

• Fatigue Symptom Checklist (FSCL)
• Multidimensional Assessment of Fatigue (MAF) Fatigue Inteference subscale, Question 1
• Profile of Mood States (POMS) Short Form Fatigue/Inertia subscale 

Controlling for baseline fatigue scores, there were no statistically significant differences in fatigue or fatigue interference between the treatment and control groups. There was no relationship between anemia and fatigue at baseline, although changes in anemia over the course of the study were modestly but significantly correlated with one measure of fatigue.

• No power analysis was provided; it was unclear if the study was appropriately powered to detect a difference in fatigue.
• Anemia was not included as a covariate in the analyses.
• Six patients withdrew due to side effects, such as nausea and headache.

There were costs related to drug acquisition.

To test whether providing information about the expected efficacy of acupressure bands would enhance their effectiveness in reducing nausea

• Chemotherapy naïve patients completed baseline questionnaires then received acupressure wristbands.
• Patients were randomized to the following groups.
  • 1: neutral handout and neutral compact disk (CD)
  • 2: acupressure-enhancing handout and neutral CD
  • 3: neutral handout and acupressure-enhancing CD
  • 4: acupressure-enhancing handout and acupressure-enhancing CD
• Patients were instructed to use the acupressure wristband and CD as needed during chemotherapy to prevent or alleviate nausea.
• Patients recorded antiemetic use, severity of nausea and vomiting, and wristband and CD usage in diaries.

• The study consisted of 74 participants.
• Mean age was 51.5 years with a range of 28–74.
• All participants were female patients with breast cancer.
• The majority of patients were White (93%), married (76%), had graduated from high school (99%), and had graduated or attended college (66%).
• The majority of patients were receiving doxorubicin-based chemotherapy (82%). The remaining were receiving docetaxel combined with either cyclophosphamide or carboplatin.

The study was conducted in a single outpatient setting. The location was not stated.

All patients were in active treatment.

This was a double-blind, four-arm, randomized, clinical intervention study.

• Patients reported their experiences in diaries.
• A nausea tool developed by Burish and Carey was used to measured nausea and vomiting on a 7-point Likert-type scale. No reliability or validity information was provided.
• Patients rated nausea expectancy on a 5-point Likert-type scale.
• Patients rated wristband effectiveness expectancy on a 5-point Likert-type scale.
• A study data questionnaire was used to gather demographic and clinical information.
• A feedback questionnaire evaluated the use of and recommendations for the acupressure wristband and CD.

• Results indicated that 15% of the sample experienced vomiting.
• The interaction of high-versus-low levels of nausea expectancy and neutral-versus-enhanced intervention showed a statistically significant difference for peak nausea (p = 0.030) but not for average nausea (p = 0.084).
• Patients who received the neutral materials took more antiemetic than patients who received the acupressure enhancing materials (p = 0.003).
• Expected nausea correlated with average nausea (p = 0.014) and peak nausea (p = 0.002).

Patients with enhanced information required less antiemetics and had less nausea than patients with neutral information. Managing expectations may facilitate chemotherapy-induced nausea and vomiting (CINV) management.

• The sample size was small with fewer than 100 patients.
• Differences in the types of chemotherapy and antiemetic medications and providers' discussion about nausea could have affected the study outcomes.
• The placebo effect of nausea intervention could have modified patients' expectations and response to the treatment.

This study illustrates the need for nurses to assess and be aware of patient’s nausea expectations during chemotherapy. Patients with high expectations may benefit from information or discussion of the expected benefits of interventions on reducing nausea.

Patients receiving doxorubicin and cyclophosphamide were randomized to one of three arms.

• Active acustimulation
• Sham acustimulation
• No acustimulation

Participants were told to wear the assigned band and adjust the acustimulation dial to increase or decrease the acustimulation; they could wear the band as frequently as desired over five days.

• The study consisted of 96 patients.
• All patients were women with breast cancer on the second cycle of chemotherapy.
• Patients’ mean age was 49.5 years.
• The majority of patients were white (n = 87).
• The majority of patients (93%) took some type of antiemetic following treatment.

All participants were treated at outpatient centers at one of four Rochester, NY, area cancer centers.

The study design was a randomized, three-arm trial.

• Demographic information and details of prior nausea and vomiting experience were recorded.
• Five-point Likert-type questions were assessed at the time of randomization following a one-minute trial of the band.
• Patient report diaries were used to measure nausea and emesis over the five-day period.
• The severity of nausea and vomiting episodes, as well as antiemetics, were recorded.
• Quality of life was measured with the Functional Assessment of Cancer Therapy Scale-General.

No significant differences were found in any study measures among the three treatment conditions.

The study does not support the use of acustimulation bands as an adjunct to antiemetics in female patients with breast cancer.

• Only women were included in the study.
• The band could be viewed as a reinforcer (negative conditioning effect) and reminder of an unpleasant state.
• Patients with brain metastases, bowel obstructions, or cardiac pacemakers, or those undergoing concurrent radiation therapy or interferon therapy were excluded.