STUDY PURPOSE: To evaluate the efficacy and safety of Goshajinkigan for prevention of CIPN

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: SCOPUS, Ovid, Medline, Cochrane Central Register of Controlled Trials, ICHUSHI, Google Scholar 

YEARS INCLUDED: Not specified

INCLUSION CRITERIA: Randomized controlled trials, cluster-randomized, crossover, and quasi-randomized trials evaluating goshajinigan for CIPN; studies needed to include adult patients (aged 18 years or older) receiving hospital-based chemotherapy

EXCLUSION CRITERIA: Articles that did not meet this criteria

TOTAL REFERENCES RETRIEVED: 1,345 originally; 9 selected for full-text review; 5 included in the final analysis

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Potential biases were evaluated for each study using methods described in the Cochrane Handbook for Systematic Reviews of Interventions

FINAL NUMBER STUDIES INCLUDED: 5

TOTAL PATIENTS INCLUDED IN REVIEW: 386

SAMPLE RANGE ACROSS STUDIES: 10-182

KEY SAMPLE CHARACTERISTICS: Three of the studies were in colorectal cancer and two in breast cancer; three focused on oxaliplatin, one on paclitaxel, and one on docetaxel; two studies did not include a comparison, two compared goshajinigan to placebo, and one compared goshajinigan to Vitamin B12

PHASE OF CARE: Active anti-tumor treatment

Goshajinkigan did not reduce the incidence of grade 2 or 3 CIPN in studies that reported CTCAE results.

The article reports trends toward decreased risk of developing grade 2 or 3 CIPN in studies using neurotoxicity criteria of debiopharm; however, these findings were not statistically significant. 

No severe adverse events seen with Goshajinkigan.

Goshajinkigan did not influence the response to chemotherapy.

This article does not provide evidence to support the use of Goshajinkigan for prevention of CIPN

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

Based on this meta-analysis, Goshajinkigan should not be recommended to patients. Further study, using rigorous, randomized, double blinded methods and large sample sizes are needed.

To explore the effect of a moderate-intensity, home-based, six-week progressive walking and resistance exercise program on chemotherapy-induced peripheral neuropathy (CIPN) symptoms, and factors that predict CIPN and moderate the effects of exercise on CIPN, in patients with cancer receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy, compared to standard of care.

Control condition: Standard care wait list control. Received the same number of follow-up visits as the exercise group.

Exercise for Cancer Patients (EXCAP) intervention: Moderate-intensity, home-based, six-week progressive walking and resistance exercise program developed by the American College of Sports Medicine.

• Walking dose: Low/moderate-intensity (60%-85% heart rate reserve) daily. Tailored based on individual’s baseline steps per day; increase steps per day by 5%-20% each week
• Resistance training dose: Theraband (resistance at 3-5 rating of perceived exertion [RPE]) daily. Ten required and four optional upper and lower extremity exercises (e.g., squats, biceps curl). Tailored progression up to four sets of 15 reps and in theraband resistance each week 
• Duration: Six weeks
• Materials provided to the patient: Pedometer, three resistance bands, and manual
• Visits: One 60-minute intervention orientation session in the clinic on the patient’s first day of chemotherapy
• Interventionist: Clinical research associates who had no professional exercise qualifications but received brief training in the EXCAP by an ACSM-certified exercise professional

• N = 355   
• AGE: Mean age = 55.8 years (SD = 10.8; range = 28-79 years)
• MALES: 7.32%  
• FEMALES: 92.68%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Stages I-IV of primarily breast (79%) but also lymphoma, colon, lung, and other types of cancer; receiving taxanes (61.4%), platinums (11%), and/or vinca alkaloids (5%), but chemotherapy naïve at baseline. Mean baseline neuropathy on 0-10 NRS was 0.9 (SD = 1.9) (numbness and tingling) and 0.8 (SD = 1.9) (hot/coldness in hands/feet); 29.6% of patients reported any numbness and tingling in hands/feet.
• OTHER KEY SAMPLE CHARACTERISTICS: Inactive (in precontemplation, contemplation, or preparation per the Exercise Stages of Change) at baseline. Karnofsky performance status ≥ 70% (mean = 94.6, SD = 7); 85.91% received prior surgery; less than 3% received XRT and/or hormone therapy; 67% were employed and 64.22% were married.

• SITE: Multi-site   
• SETTING TYPE: Home    
• LOCATION: James P. Wilmot Cancer Center at University of Rochester Medical Center, NY, and 20 NCORP community oncology practice sites throughout the United States.

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

Secondary data analysis of a multi-site non-blinded randomized controlled trial (originally designed to evaluate the effects of the intervention on fatigue)

Collected at baseline and after the intervention (at six weeks):

• CIPN symptoms: 0-10 NRS of (a) numbness/tingling, and (b) hot/coldness in hands/feet in the past seven days
• Exercise adherence: Daily exercise diary self-reported pedometer steps, minutes of resistance exercise, and RPE rated on 1-10 scale

CIPN symptoms (NRS) progressed in both groups throughout chemotherapy (all p ≤ 0.027). However, NRS of numbness/tingling (p = 0.061; β = 0.42, CI [-0.85, 0.02]) and hotness/coldness in the hands/feet (p = 0.045; β = -0.46; CI [-0.01, -0.91]) were less severe in the intervention group at six weeks; 36.5% of intervention group participants and 49.2% of control group participants reported some numbness/tingling (NRS > 0) at six weeks. 

Baseline neuropathy (NRS), female sex, and non-breast cancer predicted greater increase in CIPN (p < 0.05). Male participants responded better to the exercise intervention than female participants (p = 0.028)

Intervention group participants increased their mean daily steps by 649 (0.32 mi) to a mean of 4,820 steps per day, and the control group participants decreased in daily steps to 4,285 steps per day. The intervention participants’ steps per day were significantly higher than the control group’s at six weeks (p = 0.019). Intervention participants performed significantly more days of resistance band exercise (~ 3.5 days per week) than controls (p < 0.001).

This study provides preliminary evidence, suggesting that progressive light/moderate-intensity walking (prescribed based on step counts) and elastic band resistance training daily may reduce CIPN progression during the first six weeks of neurotoxic chemotherapy treatment.

• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Secondary analysis originally aimed to evaluate effects of exercise intervention on physical activity, fatigue, cognitive impairment, and inflammation in 619 patients receiving chemothearpy. Although the 0-10 NRS is a gold-standard measure of pain, its one-item validity and reliability in measuring CIPN is questionable. No control/stratification for comorbidities that could influence CIPN, such as diabetes and the type and cumulative dose of neurotoxic chemotherapy received. Participants who withdrew from the study were older, and had greater fatigue and a lower education level at baseline (all p ≤ 0.019). More participants in exercise group withdrew compared to control group participants (p = 0.01). Questionable interpretation of the results; the authors frequently described the results as significant when the p was > 0.05 (their two-tailed significance α).

Light/moderate-intensity aerobic and strength training exercise is safe and may be beneficial for reducing CIPN in individuals receiving chemotherapy treatment; however, further research is needed to rigorously test the effect of various dosages of specific types of exercise on CIPN and evaluate the most feasible interventions that result in maximum adherence.

STUDY PURPOSE: To evaluate current research evidence for exercise protocols effect on CIPN symptoms, balance control, physical function, and QOL

TYPE OF STUDY: Systematic review (no meta-analysis conducted)

DATABASES USED: Medline, Scopus, Bandolier, PEDpro, and Web of Science

YEARS INCLUDED: (Overall for all databases) This was not specified

INCLUSION CRITERIA: Studies that had physical exercise intervention and QOL or a balance evaluation, structured exercise protocol for patients with cancer with CIPN was preferable, English peer-reviewed and indexed manuscripts, comparisons of pre-/postintervention of cancer diagnosis, one or both genders, and all races/ages. 

EXCLUSION CRITERIA: Cross-sectional studies, case reports, published abstracts, dissertation materials, conference presentations

TOTAL REFERENCES RETRIEVED: N = 2221

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Literature search was clearly outlined but did not use standardized methodology (i.e., PRISMA); two reviewers independently examined abstracts, full manuscripts analyzed for eligibility and independently used the modified Cochrane Collaboration Back Review Group checklist to evaluate quality of studies on nine criteria and strength of evidence; high quality was determined if study met at least 5 out of 9 criteria, low quality was less than 5 out of 9; final quality score discussed between both reviewers for final determination of quality score, third researcher consulted for any discrepancies; extraction of data based on categorization for this study outcomes: CIPN symptoms, static balance control, dynamic balance control and quality of life and physical function

FINAL NUMBER STUDIES INCLUDED: N (studies) = 5 (2 of 5 were randomized studies, of high quality, three non-randomized and low quality) 

TOTAL PATIENTS INCLUDED IN REVIEW: 147 (25 dropouts) (n = 122)

SAMPLE RANGE ACROSS STUDIES: 14-56 years

KEY SAMPLE CHARACTERISTICS: All participants with a diagnosis of malignancy; all had peripheral neuropathy before starting the intervention; age range = 44-71.82 years (one study of older adults, four studies of mid adult); 84 females and 63 males; 131 participants were undergoing chemotherapy out of 147 before dropouts. In three studies, 100% of participants were actively undergoing chemotherapy; in two studies, 54% of participants were undergoing chemotherapy. Three studies evaluated CIPN supervised training intervention and two studies evaluated home-based intervention. Exercise types included aerobic walking/cycling, strength/elastic band training, calisthenics, core stability, sensory motor, and specific balance training alone or in combination. Exercise dosages ranged from 30 to 60 minutes per sessions, two to five times per week, for 3 to 36 weeks.

PHASE OF CARE: Multiple phases of care

APPLICATIONS: Elder care; palliative care

Three of four studies showed some modest improvement in CIPN with exercise; some small improvements found with exercise for static balance in all four studies; dynamic balance control evaluated in two studies, only one showed improvement with exercise; three of four studies showed improvements in QOL.

This systematic review of a small sample of five studies showed varying exercise interventions, with differing dose and duration of therapy, enhanced QOL and improved balance. However, this evidence synthesis is scant and drawing conclusions for practice would be premature as the majority of studies are of low quality. This systematic review highlights that more research is needed to determine specific exercise interventions targeted to specific cancer populations to understand the full benefit of exercise as an intervention strategy to reduce CIPN symptoms and related quality-of-life issues.

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

Other: poor choice and limited list of key terms in search strategy; literature search strategy and inclusion criteria did not specify year of studies, CIPN symptom outcome was not an inclusion criteria; study design and methodologies differed, control conditions of studies not adequately explained; different exercise interventions and time frames, different instruments across studies for outcome measures, including CIPN six, static/dynamic balance control, and QOL, some data does not fully represent the construct/categorization of study outcome measures. One study measured fear of falling substituting this as a QOL measure; one study did not measure QOL at all, one study did not evaluate CIPN symptoms as an outcome; cancer diagnoses/stage and type or number of chemotherapy regimens not specified; no effect sizes reported; only one study using intent to treat analysis; no data extraction or study reporting of adverse events of exercise interventions; selection bias in three of five studies

Exercise is a promising strategy in the management of CIPN; however, it is an understudied intervention. Large multi-center RCTs are needed to investigate specific types, doses and duration of exercise interventions tailored to specific cancer populations for CIPN, and related QOL outcome measures to identify best practices that can improve CIPN and related QOL needs.

To evaluate a nursing care model (automated symptom-monitoring and coaching system including NP follow-up of moderate to severe symptoms) to reduce CIPN symptoms.

Patients on taxane/platin therapies called an automated telephone symptom-monitoring system (SCH) daily to report symptoms of numbness and tingling. The system recorded severity, distress, and activity interference on a 0-10 scale. Patients in the telephone-monitoring group received automated self-care strategies and an NP-provided guideline-based care for symptoms rated as 4 or greater. Patients in the usual care group were instructed to call their oncologist for symptom management.

• N = 252 (238 completed the study)
• AGE: Mean age = 55.1 years (SD = 11.3)
• MALES: 51  (21.4%)
• FEMALES: 187 (78.6%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Treatment plan of a minimum three cycles of chemotherapy–any disease
• OTHER KEY SAMPLE CHARACTERISTICS: Must be receiving taxane- or platin-based chemotherapy

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Utah and Vermont

PHASE OF CARE: Active anti-tumor treatment

Secondary sub-analysis of a randomized controlled trial

Symptom severity measured daily on a 1-10 scale with 10 being most severe. SF-36 and a detailed chemotherapy treatment data sheet were updated monthly. Secondary outcomes were distress associated with numbness and tingling, interference with activities of daily living, and helpfulness of self-care strategies–all scored on a 1-10 scale. Associated symptoms and use of other services were also measured.

The SCH group experienced significantly less symptoms of numbness and tingling and the number of days with neuropathic symptoms of any severity was lower in the SCH group (10.3 versus 17.8, p = 0.02). In addition, the SCH group had less moderate symptom days and less severe days (p < 0.001 and p = 0.006, respectively). Similar trend was seen in distress related to numbness and tingling. NPs called 3.2% of days in the SCH group. For the usual care group, despite 11% of days reporting symptoms 4 or greater, no participants called their HCP for symptom management.

This proactive symptom monitoring intervention was effective in monitoring and intervening for symptoms related to CIPN. Automated self-care strategies for all intervention patients and guideline-based intervention by an NP led to less moderate and severe symptom days in the intervention group. Despite reporting 11% of days with moderate or severe symptoms, no patients in the usual care group called their healthcare provider for symptom management.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Other limitations/explanation: Due to the large number of women with breast cancer, the study was predominately female which limits generalizability to men. Specific strategies patients used to manage symptoms were not collected.

Routine monitoring of symptoms using PROs can be completed in a variety of ways and is an actionable tool to improve patient outcomes. This study highlights that patients do not frequently call their HCP when experiencing symptoms and that a proactive approach using a phone-based automated symptom assessment intervention holds promise in symptom management.

Evaluate the effect on pregabalin given three days prior and three days after each oxaliplatin dose on oxaliplatin-induced peripheral neuropathy

Pregabalin versus placebo given three days prior to and three days after oxaliplatin infusion on weeks 1, 3, and 5 of an 8-week cycle.

• N = 199 enrolled, 143 in the final analysis (56 participants did not receive at least one full cycle of FOLFOX 
• AGE: Median = 57 years (mean = 57.13, SD = 10.51)
• MALES: 99 patients (49.7%)  
• FEMALES: 100 (50.3%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: CRC, newly diagnosed stage III/IV
• OTHER KEY SAMPLE CHARACTERISTICS: Dose of pregabalin was 150-600 mg daily; placebo was also 150-600 mg daily with drug 1 and 150 mg  dose for drug 2.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Multiple sites; Sao Paulo, Brazil

PHASE OF CARE: Active anti-tumor treatment

Randomized, placebo controlled trial

Main outcome was pain level based on the visual analog scale (rating 0-10) and the brief pain inventory (BPI). Secondary endpoints  were the presence of pain from neuropathy as well the severity of pain based on the Douleur Neuropathique–4 (DN-4), the short-form McGill Pain Questionnaire (MPQ), the Neuropathic Pain Symptom Inventory (NPSI), and any changes in the nerve conduction studies as well as subjective side effect profile.

The pain intensity level of the pregabalin group was 1.03 (95% CI [0.76, 1.26]) and was 0.85 in the placebo group (95% CI [0.64, 1.06]). Quality-of-life scores did not differ between the two groups (placebo QOL was 76.9 [SD = 23.1] and the pregabalin QOL was 79.4 [SD = 20.6]). There were no significant differences in any of the outcome measures.

The intervention was safe, but did not decrease the pain severity or incidence of oxaliplatin-induced peripheral neuropathy.

• Findings not generalizable
• Other limitations/explanation: Only relevant to oxaliplatin

Pregabalin may be safe to take, but does not prevent neuropathy in those receiving oxaliplatin.

To explore the long-term effects of electroencephalographic neurofeedback (NFB) to treat CIPN and other symptoms in cancer survivors.

NFB was given in 20 sessions over a maximum of 10 weeks with rewards for voluntary changes in electroencephalography. For the NFB, sensors were placed on participants scalp in areas deemed important via the EEG assessment. During the sessions, the participants were seated in a comfortable chair and instructed to watch a computer monitor. Feedback occurred when patricians were able to keep the amplitude of a desired EEG waveform above a certain threshold, while inhibiting amplitude of other less-desired waveforms, resulting in emotionally neutral pictures. When thresholds did not match, the game paused, and no feedback was given. Over time, the brain learns to modify its activity under the sensors without input from the NFB system.

• N = 71 (62 with final data for analysis)
• AGE: Mean age = 62.5 years (SD = 10.3)
• MALES: 13%  
• FEMALES: 87%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Any cancer type was eligible
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had at least grade 3 neuropathy rating based on the NCI grading criteria or had severe pain without grade 3 neuropathy but had symptoms of neuropathy for a minimum of three months after chemotherapy completion. All post treatment.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Houston, TX

PHASE OF CARE: Late effects and survivorship

Randomized controlled trial

Symptom measurements were assessed at baseline, end of treatment, and 1 and 4 months later. They included the BPI-SF, pain quality assessment scale, MDASI, MOS-SF, BFI, Pittsburgh Sleep Quality Index. Each patient had an EEG at baseline and end of treatment.

The NFB group had greater improvement in worst pain and symptoms such as numbness, cancer-related symptom severity, symptom interference, physical functioning, general health and fatigue compared to patients in the wait list control group. There was a significant difference in pain at end of treatment (p < 0.05) and 1 month (p < 0.05) for the NFB group, no significance at 4 months. NFG group reported significant improvement in physical component subscale (p = 0.035); physical functioning (p = 0.037); and general health (p = 0.04) by the end of treatment, no difference at 1 or 4 months. There was also a significant group difference in fatigue at the end of treatment (p = 0.005). There was no effect of NFB on sleep at any timepoint. Large and moderate effect sizes were seen in neuropathic symptoms and QOL measures.

NFB has the potential to have lasting effects on CIPN symptoms as well as symptom burden, QOL, fatigue, and symptom interference.

• Small sample (< 100)
• Risk of bias (no control group)
• Intervention expensive, impractical, or training needs
• Missing data in both groups

NFB can significantly reduce symptoms without the adverse effects that medications may have. These results are promising and warrant further research.

To investigate the efficacy of minocycline for the prevention of CIPN and acute pain syndrome in patients receiving paclitaxel.

Minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo during 12 weeks of paclitaxel therapy. Treatment with minocycline/placebo stopped one week after paclitaxel.

• N = 47 (45 with final data)
• AGE: Mean age was 54.9 years (SD = 10.9)
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: 13 sites, including Mayo in Minnesota, North Carolina, North Dakota, Illinois, and Rhode Island. Authors are from these locations. Not specified in the article exact location of sites.

PHASE OF CARE: Active anti-tumor treatment

Randomized controlled trial

Patients completed a symptom pain measure and potential minocycline toxicities measure at baseline. APS symptoms were measured with a daily log of 10 items regarding pain symptoms and the use of pain medications on days 2-7 following each paclitaxel dose. On the eighth day, a 15-item questionnaire regarding symptoms was administered. CIPN was measured using the EORTC CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and then monthly after treatment ended for six months.

Significant difference in daily average pain score favoring the minocycline group (median = 96 versus 84.3, p = 0.02) and also a trend toward improvement in the daily worst pain score over the 12 cycles (p = 0.06). Also, aches and pains were less distressing (p  =0.02) and there was a trend toward less use of opioids (p = 0.05) in the minocycline group. There was no difference in the overall CIPN sensory subscale between groups or any difference in tingling, numbness, shooting/burning pain during treatment or for six months after treatment. No reports of minocycline toxicity. Patients who took minocycline reported significantly less fatigue (p = 0.02).

Minocycline in this study decreased APS symptoms but did not impact CIPN symptoms. An incidental finding was that the minocycline group had significantly less fatigue. Symptoms of APS have been reported in up to 71% of patients on 70-90 mg/m² of paclitaxel, and no agent has previously been shown to decrease these symptoms; however, analgesics are effective in alleviating the pain.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Measurement/methods not well described
• Other limitations/explanation: No report on adherence to minocycline. Sample consisted of women with breast cancer

Minocycline may be effective in reducing the symptoms of acute pain syndrome in women receiving paclitaxel therapy for breast cancer. No difference was seen in CIPN symptoms between the intervention and placebo group. Additional research is needed on women receiving higher doses of paclitaxel and to identify the impact of minocycline on treatment-related fatigue.

Investigate whether photobiomodulation (PBM) reduced peripheral neuropathy symptoms in patients with CIPN and determine if the addition of physical therapy to PBM would improve results.

Treatments of PBM, administered three times per week for six weeks, 30 minutes per visit, with treatments administered via handheld wand at a distance of 1 cm from the skin for 1-12 minutes over any of the up to 36 specified areas on the body. The sham group were exposed to a laser which generates a sense of warmth. The PBM+PT group received PBM plus physiotherapy of manual soft tissue mobilization at each treatment visit for 15 minutes along with instructions for home stretches to be performed twice daily.

• N = 70   
• AGE: No mean age noted in the study; largest percentage of participants were aged 61-70 years (45.7%)
• FEMALES (%): 100
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Sample is primarily patients with breast or gynecologic cancer treated with chemotherapy not within the last 30 days
• OTHER KEY SAMPLE CHARACTERISTICS: Primarily Caucasian

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: University of Minnesota

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

Prospective, double-blind, randomized, sham-controlled

Data collected via modified total neuropathy score (mTNS) to measure change in overall score from baseline, 4, 8, and 16 weeks.

PBM group had statistically significant improvement in mTNS score (-6.8 points; -52.6%) from pretreatment to eight weeks after initiation of treatment (p < 0.001). Sham group had no evidence of improvement in mTNS score. Thirty-eight of the sham group patients crossed over to the PBM+PT group. This group experienced a significant improvement (-6.9 points; -50.9%) in mTNS score (p < 0.001) from baseline. The difference in mean mTNS reductions between PBM and PBM+PT was 0.1 (p = 0.85), indicating the addition of PT to PBM did not improve neuropathy symptoms more than PBM alone. Both the PBM and PBM+PT group experienced modest regression in mTNS scores by week 16. Only one complication was observed with one patient experiencing a second-degree burn in the sham control group. There were no complications noted in patients receiving PBM.

PBM was shown to be an effective intervention for CIPN, with 90% of patients experiencing significant improvement in mTNS scores. This is a positive result in the sample population. There was a high compliance rate and low dropout rate in this study, contributing to the validity of the findings. Long-term benefits beyond 16 weeks are not known.

• Small sample (< 100)
• Risk of bias (sample characteristics): all females, primarily breast/gynecologic cancers, primarily Caucasian
• Other limitations/explanation: Impact of other concurrent treatments for CIPN were not considered; optimization of treatment algorithm. Treatment must be administered by a certified laser technician, which may not be available in all settings.

Need for further research on this intervention and awareness of nonpharmacologic interventions which may impact neuropathy symptoms.

This study investigates the connection of providing an eight-week guided multimodal exercise class twice a week to patients with metastatic colorectal cancer in hopes of influencing their chemotherapy-induced peripheral neuropathy.

30 outpatients with metastatic colorectal cancer and with a history of chemotherapy treatment were recruited to participate in a randomized control trial. The intervention group participated in an eight-week supervised multimodal exercise class twice a week/60 min. This class included endurance, resistance, and balance training. The control group was given written recommendations to complete physical activity. Chemotherapy-induced peripheral neuropathy was measured using the FACT/COC-NTX questionnaire. Endurance capacity, strength, and balance were also measured at three separate intervals: before, after, and four weeks post-study.

• N: 30  (24 completed the study) 
• AGE: The mean age of the intervention group was 68.53 years. The mean age of the control group was 70 years (NS)
• MALES: 21 (70%) 
• FEMALES: 9 (30%) 
• CURRENT TREATMENT: Chemotherapy, other
• KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Germany

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

Randomized control trial

• FACT/GOG-NTX questionnaire for chemotherapy-induced peripheral neuropathy
• 6MWT for endurance measurement
• H1RM for strength measurement
• GGT-Rehab for balance measure

The study showed significant improvement in neuropathic symptoms in the intervention group compared to worsening symptoms in the control group (p = 0.023). Increase of balance was noted between groups (p = 0.048) along with static balance (TOI, p = 0.022; NXT, p = 0.006). The intervention group noted an increase in strength from baseline: bench press (p = 0.006), leg press (p = 0.002), and lat pull down (p < 0.001)

The implementation of a multimodal, supervised exercise program showed significance in counteracting the neuropathic symptoms related to chemotherapy, increasing muscle strength and increasing balance in patients with metastatic colorectal cancer.

• Small sample (< 30)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Unclear which exercise modality is responsible for the positive results.

Patients at risk for chemotherapy-induced peripheral neuropathy (CINP) could benefit from a supervised multimodality exercise class to counteract the worsening effects of CINP. Providing your patients with written instruction for exercise might not be enough of an intervention to combat the worsening of this side effect.

STUDY PURPOSE: Evaluate different methods of dexamethasone dosing with bortezomib on severity of peripheral neuropathy

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed from 2002 to June 14, 2015 and ASCO annual meeting abstracts from 2008 to June 14, 2015

YEARS INCLUDED: (Overall for all databases) as above

INCLUSION CRITERIA: (a) IV bortezomib, (b) at least 20 untreated participants with myeloma, and (c) reported grade of neuropathy

EXCLUSION CRITERIA: Not a clinical trial; studies focusing on bortezomib maintenance rather than initial treatment; retrospective studies

TOTAL REFERENCES RETRIEVED: Not included

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Studies were categorized as dexamethasone partnered with bortezomib, weekly dosing, or other dosing schedule; only clinical trials used; no other evaluation of quality mentioned

FINAL NUMBER STUDIES INCLUDED: 32

TOTAL PATIENTS INCLUDED IN REVIEW: 2,697

SAMPLE RANGE ACROSS STUDIES: Varying dexamethasone dosing schedules, 14 partnered, 6 weekly

KEY SAMPLE CHARACTERISTICS: All had multiple myeloma and were receiving initial treatment with bortezomib and dexamethasone.

PHASE OF CARE: Active antitumor treatment     

APPLICATIONS: Palliative care

Pooled grade 3 or higher PN for partnered, weekly, or other schedules were 5.3%, 11%, and 9.6%, respectively. Patients on weekly or other schedules had higher rates of grade 3 or higher PN. Overall, all grade PN for partnered, weekly, or other schedules were 45.5%, 63.9%, and 47.5%, respectively. When studies including thalidomide were omitted from the analysis, the lower incidence of grade 3 or higher PN in partnered dexamethasone dosing was still present.

Partnered dexamethasone dosing schedule (day of and day after) may result in less severe PN. There was consistently lower all grade and grade 3 or higher PN with partnered dosing when compared to other dosing schedules.

• Low sample sizes
• Only multiple myeloma included; possible investigator bias

Nurses should be aware that, in patients undergoing initial treatment with bortezomib and dexamethasone, partnered dexamethasone may be preferred due to potentially less severe neuropathy.