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.

• N = 24
• KEY DISEASE CHARACTERISTICS: Patients with gastrointestinal carcinoma 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients receiving varying irinotecan-based regimens 

• SITE: Multi-site
• LOCATION: Four Spanish community practice settings

• Experimental, interventional, prospective study
  • No control

• Diarrhea grade, although no mention of which grading scale was used

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.

• Uncontrolled trial
• Small numbers

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.

• N = 40   
• AGE = 18 years and older
• FEMALES: 100%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: Woman diagnosed with breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Participants were aged 18 years or older, planned for mastectomy with or without axillary dissection, and were able to understand and follow protocol. Exclusions: contraindications for memantine and hypertension, severe cardiac insufficiency and/or diabetes, alcohol addiction, treatment with certain drugs, childbearing age, no use of effective contraceptive, pregnancy or lactation, involvement in another trial, inability to comply with protocol requirements

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: University Oncology Hospital, Clermont-Ferrand, France

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

• Randomized, single-blind, placebo controlled trial

• Numerical rating scale
• Brief Pain Inventory (BPI)
• McGill Pain Questionnaire (MPQ)
• Neuropathic Pain Diagnostic Questionnaire (DN4)
• Neuropathic Pain Symptom Inventory
• Trail Making Test (TMT)
• Digit symbol substitution test (DSST)
• Leeds Sleep Evaluation Questionnaire (LSEQ)
• Quality of life by the SF-36
• Surgical- and chemotherapy-induced neuropathic pain were differentiated.

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.

• Small sample (< 100)
• Findings not generalizable
• Not generalizable to all chemotherapy patients nor surgical patients for treating neuropathic pain

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.

• FINAL NUMBER STUDIES INCLUDED = 12
• TOTAL PATIENTS INCLUDED IN REVIEW = 442
• SAMPLE RANGE ACROSS STUDIES = 12–107 patients
• KEY SAMPLE CHARACTERISTICS: Although education status may influence neuropsychological test results, only half of the studies provided this information. Likewise, menopausal status may affect cognition, and this was only reported by two thirds of the studies.

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.

• A small number of studies (n = 12) were included in the review for multiple types of interventions.
• Only one study had a sample size greater than 100 (range = 12–107).
• Studies of low quality were included. 

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. 

To determine the effectiveness of a physician-centered communication skills training program on anxiety levels in patients with cancer. A three-phrase, multicenter, quasi-experimental study was used.

The intervention phase of the study invited physician participants in the treatment group to attend a skills program to improve communications knowledge and strategies. The intent of the communications training was to improve communication with patients with cancer and families. The training sessions, taught by psycho-oncologists, were held at each study center and were scheduled in three-hour sessions for three weeks to total nine hours of training. Each physician participant was emailed relevant scientific papers (two published, one unpublished) five days in advance of each three-hour session. The treatment group physician participants were asked to read the materials in preparation for sharing during the training. Each session included didactic, experiential learning, and group discussion including clinical cases and role play. There was no communications training for physician participants from the control group.

• N = 36 physicians (17 in the treatment group and 19 in the control group) and 339 patients (174 in the control group and 165 in the treatment group)    
• MEAN AGE = physician: 46.64 years (SD = 7.9), range = 38.74–53.64; patient: 61.2 years (SD = 13.61), range = 47.59–74.81
• MALES: physicians, 47%; patients, 45%; FEMALES: physicians, 53%; patients, 55%
• KEY DISEASE CHARACTERISTICS: None, intervention was focused on physicians. Patients seen by control and intervention physicians varied widely in age, cancer type and cancer stage/prognosis.
• OTHER KEY SAMPLE CHARACTERISTICS: Physicians were oncologists, hematologists, with a median of 15 years of professional experience, from northern, central and southern Italy, equally. Nineteen had no prescribed training in physician-centered communication; 17 attended training. There was no difference in pre-consultation anxiety scores between the 339 patients enrolled in the two groups. 

• SITE: Multi-site    
• SETTING TYPE: Multiple settings  
• LOCATION: Italian oncology practices

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics, elder care, palliative care 

Multi-center, quasi-experimental, three-phase study. Of note, the phases of the study, as described, are not phases as used in North American scientific study. Rather, they are components of the methodology. Specifically, the authors describe phase 1 as recruitment, phase 2 as intervention, and phase 3 is evaluation.

• Physician demographics and professional training
• Patient demographics and communication documentation (physician self-report)
• Anxiety in patients was measured by the Psychological Distress Inventory (PDI) and completed before the consultation.
• STAI-S (State-Trait Anxiety Inventory-State) was completed before and after the consultation.

Suggestion of effectiveness of a communication skills training program with reference to patient anxiety levels.  Further research needed.

• Small sample (less than 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Needing to train physicians, expensive, time constraints. Patients were blinded to physician group allocation. Physician communication performance may be skewed (possible Hawthorne effect) because of tendency to improve on each subsequent patient communication encounter when the evaluation form was completed.

Implications were difficult to ascertain because the intervention was physician-based. The authors indicated a need to explore if nurse training in communication would be beneficial.  Also discussed was the difference in communication styles between oncologists and oncology nurses and the effect on anxiety.

Examined efficacy and toxicity of gabapentin when taken for additional 8 weeks after previous study, where it was compared 3 different doses of gabapentin with placebo for treatment of hot flashes due to androgen deprivation therapy

Self completed report by participants

• N :  Evaluable 147, data for 117 
• AGE: Mean 69.4 years old
• MALES: (%) 100% males    FEMALES: (%) NO
• KEY DISEASE CHARACTERISTICS: Prostate cancer  
• OTHER KEY SAMPLE CHARACTERISTICS:  
  • Men with history of prostate cancer, on stable androgen deprivation therapy,  experiencing troublesome hot flashes
  • No renal insufficiency or previous used of gabapentin or concurrent use of any other chemotherapy or hormone treatment
     

SITE: Mutli-site    
 

PHASE OF CARE: Transition phase after initial treatment

APPLICATIONS: Late Effects & Survivorship; End of Life and Palliative Care
 

Observational, open label, and uncontrolled design continuation of randomized study

• Patients received a booklet containing instructions     
• Patients received a set of hot flash diaries to be completed daily
• Patients received symptoms experience diaries to be completed weekly, addressing adverse effects: decreased appetite, nausea, dry mouth, dizziness, fatigue, trouble walking or balance problems, muscle pain, difficulty with concentration, constipation, sleepiness/sleep problems, blurred vision, anxiety, and mood changes; also included quality of life and satisfaction with hot flash control (0 none to 10 worst)
• Quality of Life measured by the Profile of Mood States-Brief (POMS-B)- baseline week and after he 4 weeks of treatment
   

 600 mg/d  of gabapentin moderately decreased the hot flash score without substantial toxicities.  All groups decreased hot flash scores and frequency at similar levels. Appetite loss and constipation were not increased. Troubled sleeping and nervousness scores were better in the placebo group.

• Gabapentin moderately decreases hot flash scores and frequencies without important toxicities over 8 weeks. 
• Doses of 600-900 mg/d of gabapentin show better results for treating hot flashes than 300 mg/d.

•  Continuation phase:  observational, open label, and uncontrolled

• Results from the study should be cautiously generalized because of patient subjective ratings.
• The study was not controlled or randomized.
• There was some possible recruitment bias for those patients with better adherence to medical instructions.

To evaluate the efficacy of long-acting methylphenidate in alleviating cancer-related fatigue (CRF), assess tolerability, and determine the effects on quality of life (QOL) in patients with CRF. Prior studies of methylphenidate have yielded mixed results. The drug used here was a mixture of d and l isomers of methylphenidate.

Patients were stratified according to disease stage, baseline fatigue scores, and whether they were receiving concomitant cancer treatment. They were then randomized to receive methylphenidate or placebo for four weeks. Patients took one tablet (18 mg of long-acting methylphenidate) on days 1 to 7, two tablets (36 mg) on days 8 to 14, and three tablets (54 mg) on days 15 to 28. Tablets were to be taken in the morning. A standard dose modification procedure was used in case of adverse effects attributed to the study drug.

• The final evaluable sample included 125 patients (57%–60% female). 
• Patients had a history of CRF defined by a score of 4 or more on a 10-point fatigue screening scale.
• Mean age was 59.2 years (standard deviation [SD] = 11.23 years) in the methylphenidate arm and 60.6 years (SD = 13.82 years) in the placebo arm. 
• Of the patients, 29% to 38% had breast cancer across the study groups. Other diagnoses included lung, colon, prostate, and mixed cancers.
• Patients had an Eastern Cooperative Group (ECOG) performance status of 0 to 2. 
• Patients had a life expectancy of at least six months. 
• Patients were excluded if they had any other cause of fatigue, brain tumor or metastases, and psychiatric disorders, among other exclusions.

• Multisite
• Collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic

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

• Brief Fatigue Inventory (BFI), completed weekly
• Short Form 36 Health Survey (SF-36) Vitality subscale
• Weekly linear analog self-assessment items used in North Central Cancer Treatment Group (NCCTG) clinical trials for QOL measures
• Pittsburgh Sleep Quality Index (PSQI), completed at study entry and week 4
• Subject Global Impression of Change (SGIC) was completed at the end of week 4 to measure patients’ perceived improvements in QOL, physical condition, and emotional state.
• Adverse events and drug toleration were assessed with symptom experience diaries completed at baseline and weekly by patients.
• Common Terminology Criteria (CTC) v3.0 was used by providers to grade adverse events at baseline and at each weekly evaluation via weekly telephone calls.

In advanced stage disease (stage III–IV), mean improvement in fatigue was 19.7 with methylphenidate and 2.1 with placebo (p = 0.02) Early stage patients had less improvement with methylphenidate than those receiving placebo. Similar trends were seen in SF-36 measures; however, differences between groups were not statistically significant. Self-reported adverse events showed a significant increase in nervousness (p = 0.003) and appetite loss (p = 0.034) in the methylphenidate arm. Individuals in the placebo arm reported improvements in self-reported adverse effects in nervousness, shakiness, appetite loss, abdominal pain, and sex drive. Both study groups were similar in terms of gender distribution, age, disease stage, and other baseline measures.

The study demonstrated benefit for d-methylphenidate compared with placebo in alleviating CRF. Methylphenidate appeared to have some benefit in patients with advanced stage of disease.

There appeared to be some benefit of long-acting methylphenidate in patients with more advanced disease; however, these patients also experienced adverse effects. For use in these patients, benefits in terms of fatigue would need to be weighed against the adverse effects for individual patients from the patient's perspective.

The study findings suggest that further research on effectiveness, particularly in patients with more advanced disease, is warranted.

Patients with chronic lymphocytic leukemia (CLL) were assessed.

No process development or search strategy were stated.

Information was provided by the authors in regards to current trends in CLL treatment and the risk of infection that is present with the most common current treatments, such as fludarabine, rituximab, alemtuzumab, and steroids. Specific bacterial and fungal infections that are most commonly associated with treatment were discussed as well as the prevention and management of these infections. A table was provided that had the most commonly occurring infections; chemotherapy treatment most commonly associated with each infection, prophylaxis, treatment options for the infection with duration and side effects; and nursing interventions. Discussion also was included on monoclonal antibodies and risk of opportunistic infection due to immune incompetency from these agents.

• Patients with CLL that are being treated should have appropriate surveillance and examination in regard to assessing for infection, related to their specific treatment therapy. A patient with CLL with a fever should always be considered infected until proven otherwise.
• Patients receiving frontline fludarabine therapy should receive antiviral prophylaxis with famciclovir 500 mg PO BID, valacyclovir 500 mg PO qid or acyclovir 400 mg PO BID during therapy and for up to six months after therapy. Prophylactic antibiotic or antifungal therapy is not currently recommended for patients receiving fludarabine.
• Routine anti-infective prophylaxis is not recommended for patients receiving rituximab monotherapy.
• Routine anti-infective prophylaxis for patients receiving alemtuzumab is recommended, specifically trimethoprim/sulfamethoxazole (TMP/SMX) DS, TIW forprophylaxis against PCP and famciclovir, acyclovir, valacyclovir,or equivalent for antiviral prophylaxis. This therapy should continue for at least two months after treatment ends or until CD4 count recovers to 200 cells/mcl or greater. Patients should also be monitored weekly for CMV using CMV PCR serum assays.
• Patients who have an absolute neutrophil count (ANC) less than 500 and receiving alemtuzumab should receive G-CSF as prophylaxis.
• For patients with relapsed or refractory CLL receiving chemo-immunotherapy combination medications, routine incorporation of anti-infective prophylaxis may be necessary to minimize severe infection.
• If a CLL patient has a history of hepatitis B, prophylaxis with lamivudine 100 mg PO qid should begin four weeks prior to therapy, continue during therapy, and up to six months following therapy.
• No routine antifungal prophylaxis is recommended for patients with CLL.
• Patients with CLL should receive PCP prophylaxis with TMP/SMX DS TIW (alternatives are dapsone 100 mg PO five days per week), nebulized pentamadine 300 mg PO, or atovaquone 750 mg PO BID) beginning at the start of therapy and continuing for 6–12 months after therapy or until CD4 count is greater than 250 cells/mcl.
• Patients with CLL should receive vaccinations with attenuated vaccines.

No conflicts of interest were identified.

Combinations of antibacterial, antiviral, and antifungal prophylactic medications may be appropriate in patients with CLL being treated with various chemotherapy regimens to prevent a life threatening infection from occurring and the type and duration is dependent on the agents they are receiving.

Nevasic, a medical device, is an audio program that generates an antiemetic reaction. Nevasic is thought to work by emitting specific constructed tones, frequencies, and pulses that disrupt the normal auditory signal chain at the vestibular level, affecting the experience of nausea and vomiting.

This study was a pilot, multicenter, randomized, controlled trial with three parallel arms (intervention, attention, and control) in Mashhad, Iran. After randomization, all participants were given the treatment progression questionnaire. Those in the intervention and attention groups also were issued a CD player and headphones with the Nevasic program or music files. Patients could keep the equipment at the end of the study. The procedure for the intervention and attention groups were identical except that those in the Nevasic intervention group listened to the active intervention of Nevasic, and those in the attention group listened to preselected music. Participants were given clear instructions on the use of the Nevasic program or the music, which included: only listening through the headphones provided; listening to Nevasic or the music immediately once they started feeling nauseous or vomiting during or after chemotherapy administration; listening to the Nevasic or music program all the way through the 27 minutes or till they felt symptoms diminished; and not skipping any part of the Nevasic or music program. They were instructed to repeat these stages if their symptoms returned. The duration of the intervention or attention was six days. Participants in all three groups were told to take their antiemetics after chemotherapy as prescribed. The participants were instructed in the completion of the measures and follow-up questionnaire. They were asked to return the measures and questionnaires using prepaid, selfaddressed envelopes.

• N = 99 (Nevasic Arm: 34, Music Arm: 32, Control Arm; 33)  
• MEAN AGE RANGE = 46–51 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer

• SITE: Single site
• SETTING TYPE: Not specified    
• LOCATION: Mashhad, Iran

• PHASE OF CARE: Active antitumor treatment

Pilot, multicenter, randomized, controlled trial with three parallel arms (intervention, attention, and control)

• The frequency and duration of nausea and the amount of vomiting was measured using the translated (Persian) version of Rhodes Index of Nausea, Vomiting, and Retching (INVR).
• Health-related quality of life (HR-QOL) was measured with the validated Iranian version of the European Organization Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ-BR23 (Safaee and Dehkordi, 2007).

Based on these study results, Nevasic is not an effective treatment in the management of CINV. The researchers stated that the findings from the trial highlight the need for several modifications to the design and the mode of intervention delivery.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Other limitations/explanation: First, this feasibility trial was not powered to detect statistically significant differences between groups. Second, no blinding was used for this study, and participants were aware of which arm they were in.

Based on these study results, Nevasic is not an effective nonpharmacologic treatment technique to control or manage CINV.

To determine the proportion of women who experience significant treatment-induced peripheral neuropathy

Women with gynecologic cancer received combination chemotherapy consisting of cisplatin and paclitaxel via IV 175 mg/m² over three hours, followed by amifostine 740 mg/m² and cisplatin 75 mg/m² administered over 90 minutes beginning 15 minutes after amifostine administration.

• N = 29 enrolled in this limited-access study; 21 completed all six cycles of therapy plus the three-month evaluations
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Women with ovarian, primary peritoneal, fallopian tube, endometrial, cervical, or uterine sarcoma
• OTHER KEY SAMPLE CHARACTERISTICS: Proposed treatment included both cisplatin and paclitaxel chemotherapy.
• EXCLUSION CRITERIA: Prior chemotherapy or radiation or history of neuropathy

• Phase II study

• Measures were done at baseline, before each chemotherapy cycle, and three months after completion of treatment.
• Chemotherapy-induced peripheral neuropathy (CIPN) was measured using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale, neurotoxicity subscale of the Functional Assessment of Cancer Therapy and Gynecologic Oncology Group, and vibration perception threshold (VPT) testing using the Vibratron II device.

Four of 27 assessable patients experienced dose-limiting toxicity grade 2 or higher CIPN as measured by clinical assessment and NCI CTCAE grading. The number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed.

Amifostine’s level of activity was insufficient to warrant further study in a phase III trial.

• The study contained a relatively small sample size (n = 29) and used a one-group design.
• Frequent evaluations of CIPN were performed by different professionals, but a detection bias may have been present.
• Although VPT testing is considered to be the gold standard, it can be inaccurate if the same digits are not used at each assessment.
• Low inter-observer agreement (46%) was found using the NCI CTCAE.

The researchers' aim was to determine the proportion of women who experience significant treatment-induced peripheral neuropathy.

Women with gynecologic cancer received combination chemotherapy consisting of cisplatin and paclitaxel via IV 175 mg/m² over three hours followed by amifostine 740 mg/m² and cisplatin 75 mg/m² administered over 90 minutes beginning 15 minutes after amifostine administration.

Twenty-nine women enrolled in the limited-access study and 21 completed all six cycles of therapy plus the three-month evaluations. The eligibility criteria for this phase II study included having ovarian cancer and primary peritoneal, fallopian tube, endometrial, cervical, or uterine sarcoma. Exclusion criteria include prior chemotherapy or radiation therapy and having a history of neuropathy.

Measures were conducted at baseline, before each chemotherapy cycle, and three months after completion of treatment. Chemotherapy-induced peripheral neuropathy (CIPN) was measured using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) toxicity scale, the neurotoxicity subscale of the Functional Assessment of Cancer Therapy–Gynecologic Oncology Group (FACT-GOG), and vibration perception threshold (VPT) was tested using the Vibratron II device.

Four of the 27 assessable patients experienced dose-limiting toxicity (greater than grade 2 CIPN) as measured by clinical assessment and the NCI-CTCAE. The number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed. The level of activity for amifostine was insufficient to warrant additional study in a phase III trial.

The study contained a relatively small sample size (29 participants) and used a one-group design. Frequent evaluations of CIPN were performed by different professionals, but a detection bias may have been present. Although VPT testing is considered to be the gold standard, it can be inaccurate if the same digits are not used at each assessment. Low interobserver agreement (46%) was found using the NCI-CTCAE.