Griffiths, C., Kwon, N., Beaumont, J.L., & Paice, J.A. (2018). Cold therapy to prevent paclitaxel-induced peripheral neuropathy. Supportive Care in Cancer, 26, 3461–3469.
Evaluate the effectiveness of cold therapy on prevention of CIPN in those receiving paclitaxel-based therapy for breast cancer.
Patients wore glycerine-containing Elasto-Gel glove and sock on one extremity and nothing on the other extremity. Elasto-Gel glove/sock were cooled to -25 to -30 C in a freezer for at least three hours prior to administration; was worn for a total of 210 minutes, and changed every 45-50 minutes during infusion. A total of nine data points were collected.
PHASE OF CARE: Active anti-tumor treatment
Randomized controlled study of taxane-naïve patients receiving dose dense anthracycline plus paclitaxel therapy. Patients were own paired control.
Symptoms of neuropathic pain, including pain severity and sensory severity. Measured with NPSI, BPI, and QST for measurement of pain, pain severity, and sensory severity, respectively).
No significant difference in pain as measured by NPSI; all measurements of pain severity were increased with the BPI, including interference with daily activity, worst pain in the last 24 hours, average pain in 24 hours, and pain currently experienced. No significant difference in any of the five QSTs used for sensory severity, including sensitivity to innocuous touch, sensitivity to noxious stimuli, sensitivity to vibration, manual dexterity, and fine motor dexterity.
Study was stopped early at time point 6 due to high dropout rate from discomfort related to intervention; when stopped, no evidence of decreased CIPN was seen.
Education about current therapies. Further research needed on cryotherapy for prevention of CIPN.
Han, X., Wang, L., Shi, H., Zheng, G., He, J., Wu, W., . . . Wei, G. (2017). Acupuncture combined with methylcobalamin for the treatment of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma. BMC Cancer, 17, 40.
To investigate if acupuncture plus methlycobalamin is an effective treatment compared to methlycobalamin alone in reducing CIPN in patients with multiple myeloma.
Acupuncture plus methylcobalamin (Met + Acu) was compared with methylcobalamin alone to evaluate effectiveness on CIPN as measured by VAS, FACT-GOG-NTX (functional assessment of neurotoxicity) and nerve conduction velocity compared to methlycobalamin (Met) alone in patients with multiple myeloma.
Patients with multiple myeloma randomized to treatment group (Met+Acu) or control group (Met). Intervention duration for both groups was 84 days
Methylcobalamin administration protocol x 3 cycles/84 days: 1 cycle = 500 mcg IM qod x 20 days(10 injections) then two months oral met 500 mcg tid
Acu administration of protocol x 3 cycles: 1 cycle = bilateral acupuncture needles at designated acupoints (aseptic adm by senior physician (15 years of experience) at depth 0.3-1 inches x 30 minutes; initially in prone position with needle retention then administered to same acupoints in supine position x 3 days then qod x 10 days
Prospective randomized controlled trial to investigate effect of Met + Acu versus Met on CIPN, sx neurotoxicity and nerve conduction
VAS pain score (neuropathic pain); FACT/GOG-NTX questionnaire (functional assessment of neurotoxicity); EMG (nerve conduction velocity)
Evaluated outcome measures before and after treatments within and between Met + Acu and Met groups:
In 98 patients with multiple myeloma with grade 2 or higher CIPN, there was significant reduction in PN pain in Met + Acu and Met groups but more significant relief with Met + Acu. Only Met + Acu group had significant improvement in functional assessment of neurotoxicity symptoms and nerve conduction; no improvement in Met control group
Acupuncture plus methylcobalamin may relieve CIPN-related pain, function, and nerve conduction in patients with multiple myeloma. Large multi-center, randomized controledl trials are needed to validate these findings and investigate their effects related to pharmacotherapies specific to MM utilizing rigorous measurement tools and validated instruments specific to patients with MM.
Noh, H., Yoon, S.W., & Park, B. (2018). A systematic review of herbal medicine for chemotherapy induced peripheral neuropathy. Evidence-Based Complementary and Alternative Medicine, 2018, 6194184.
STUDY PURPOSE: To evaluate the evidence related to use of herbal medicine for prevention and treatment of chemotherapy-induced peripheral neuropathy
TYPE OF STUDY: Systematic review
DATABASES USED: 13 electronic databases including Medline, CENTRAL, EMBASE, AMED, China National Knowledge Infrastructure, Wanfang Database, CQVIP database, Korean Studies Information, DBPIA, Korea Institute of Science Technology Information, Research Information Center for Health Database, Korean Traditional Knowledge Portal, KoreaMed
YEARS INCLUDED: (Overall for all databases) through May 2017, no other limitations on publication date
INCLUSION CRITERIA: Randomized controlled trials that tested herbal medicine for preventing or treating CIPN. Participants in the studies were at least 18 years old, diagnosed with cancer, had received chemotherapy, and had CIPN diagnosed by clinical assessment.
EXCLUSION CRITERIA: Only the first treatment period data was analyzed for crossover trials. If the authors could not separate the results of the first and second periods in the crossover trial, they excluded the study. RCTs with unreliable or unavailable methods or results
TOTAL REFERENCES RETRIEVED: 819
FINAL NUMBER STUDIES INCLUDED: 28
TOTAL PATIENTS INCLUDED IN REVIEW: 2,174
SAMPLE RANGE ACROSS STUDIES: 31-186
KEY SAMPLE CHARACTERISTICS: Various solid tumors and one study in multiple myeloma, studies investigated oral herbals foot baths, IV, and fumigation. Oxaliplatin was used in 20 studies, paclitaxel was used in two, docetaxel was used in one, and various chemotherapy regimens were used in four studies.
PHASE OF CARE: Active anti-tumor treatment
The authors were unable to perform planned meta-analysis because of the heterogenicity of herbal treatments, doses, outcome measures, and small sample sizes.
Unable to draw any conclusions about the efficacy of herbal treatments for prevention or treatment of CIPN
No changes to clinical practice can be recommended based on this article.
Kuriyama, A., & Endo, K. (2018). Goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Supportive Care in Cancer, 26, 1051–1059.
STUDY PURPOSE: Examine whether goshajinkagin prevents CIPN in patients receiving neurotoxic chemotherapy.
TYPE OF STUDY: Meta analysis and systematic review
DATABASES USED: PubMed, EMBASE, Ichushi, Cochrane Central Register of Controlled Trials
YEARS INCLUDED: (Overall for all databases) inception through August, 2017
INCLUSION CRITERIA: Randomized controlled trials that assessed efficacy and safety of goshajinkagin in preventing CIPN; patients had to be undergoing neurotoxic chemotherapy (taxanes, vinca alkaloids, platinum agents); adult patients older than age 18 years ; prophylactic doses of goshajinkagin (7.5 g per day)
EXCLUSION CRITERIA: Patients that had already developed CIPN; dosing of goshajinkagin that was given as treatment for CIPN rather than prophylaxis
TOTAL REFERENCES RETRIEVED: 234 articles retrieved; five articles evaluable after inclusion/exclusion applied
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Five trials with 397 total patients; 3 colon cancer, 2 breast cancer
FINAL NUMBER STUDIES INCLUDED: 5
TOTAL PATIENTS INCLUDED IN REVIEW: 397
SAMPLE RANGE ACROSS STUDIES: Included patients with breast cancer or colon cancer, receiving FOLFOX 4 or FOLFOX 6, and weekly paclitaxel- or docetaxel-based chemotherapy. Studies ranged from 18-186 patients; studies ranged from 12-26 weeks in duration. Two trials with placebo comparator; two trials with no interventions for control; one trial administered mecobalamin for comparison; one trial terminated early due to incidence of increased CIPN. Two different definitions of CIPN used, those from NCI-CTCAE in four studies (measuring severity) and that from the Neurotoxicity Criteria of Debiopharm (DEB-NTC) in one study (measuring duration)
KEY SAMPLE CHARACTERISTICS: 35-88 years old; breast cancer and colon cancer
PHASE OF CARE: Active anti-tumor treatment
Overall, the use of goshajinkagin was not related to a decreased incidence of CIPN; though in the one study there was reduced incidence of grade 1 and grade 3 CIPN, but no difference in grade 2 CIPN. One study with increased incidence of CIPN (stopped early).
No evidence to support the use of goshajinkagin for prevention of CIPN.
Further research on use of the medication may be warranted. Education of patients about the inconsistent results.
Hoshino, N., Ganeko, R., Hida, K., & Sakai, Y. (2018). Goshajinkigan for reducing chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. International Journal of Clinical Oncology, 23, 434–442.
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
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.
Kleckner, I.R., Kamen, C., Gewandter, J.S., Mohile, N.A., Heckler, C.E., Culakova, E., . . . Mustian, K.M. (2018). Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: A multicenter, randomized controlled trial. Supportive Care in Cancer, 26, 1019–1028.
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.
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 (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.
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.
Duregon, F., Vendramin, B., Bullo, V., Gobbo, S., Cugusi, L., Di Blasio, A., . . . Ermolao, A. (2018). Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review. Critical Reviews in Oncology/Hematology, 121, 90–100.
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.
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.
Kolb, N.A., Smith, A.G., Singleton, J.R., Beck, S.L., Howard, D., Dittus, K., . . . Mooney, K. (2018). Chemotherapy-related neuropathic symptom management: A randomized trial of an automated symptom-monitoring system paired with nurse practitioner follow-up. Supportive Care in Cancer, 26, 1607–1615.
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.
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.
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.
de Andrade, D.C., Jacobsen Teixeira, M., Galhardoni, R., Ferreira, K.S.L., Braz Mileno, P., Scisci, N., . . . de Souza, A.M. (2017). Pregabalin for the prevention of oxaliplatin-induced painful neuropathy: A randomized, double-blind trial. Oncologist, 22, 1154–1155, e99–e105.
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.
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.
Pregabalin may be safe to take, but does not prevent neuropathy in those receiving oxaliplatin.
Prinsloo, S., Novy, D., Driver, L., Lyle, R., Ramondetta, L., Eng, C., . . . Cohen, L. (2018). The long-term impact of neurofeedback on symptom burden and interference in patients with chronic chemotherapy-induced neuropathy: Analysis of a randomized controlled trial. Journal of Pain and Symptom Management, 55, 1276–1285.
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.
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.
NFB can significantly reduce symptoms without the adverse effects that medications may have. These results are promising and warrant further research.