Pachman, D., Ruddy, K., Lafky, J., Beutler, A., Loprinzi, C., Dockter, T., . . . Sikov, W.M. (2017). A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I. Supportive Care in Cancer, 25, 3407–3416.
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.
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.
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.
Argenta, P.A., Ballman, K.V., Geller, M.A., Carson, L.F., Ghebre, R., Mullany, S.A., . . . Erickson, B.K. (2017). The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: A randomized, sham-controlled clinical trial. Gynecologic Oncology, 144, 159–166.
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.
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.
Need for further research on this intervention and awareness of nonpharmacologic interventions which may impact neuropathy symptoms.
Zimmer, P., Trebing, S., Timmers-Trebing, U., Schenk, A., Paust, R., Bloch, W., . . . Baumann, F.T. (2017). Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves balance and strength in metastasized colorectal cancer patients: A randomized controlled trial. Supportive Care in Cancer, 26, 615–624.
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.
Randomized control trial
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.
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.
Kumar, S.K., Laubach, J.P., Giove, T.J., Quick, M., Neuwirth, R., Yung, G., . . . Richardson, P.G. (2017). Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. British Journal of Haematology, 178, 756–763.
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.
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.
Hanai, A., Ishiguro, H., Sozu, T., Tsuda, M., Yano, I., Nakagawa, T., . . . Tsuboyama, T. (2018). Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: Prospective self-controlled trial. Journal of the National Cancer Institute, 110, 141–148.
To investigate the effectiveness of cryotherapy to prevent paclitaxel-induced peripheral neuropathy.
Each patient wore frozen flexible gloves and socks on their dominant hand and foot (15 minutes before paclitaxel administration to 15 minutes after the infusion was complete: 90 minutes total). Gloves were replaced after the first 45 minutes.
PHASE OF CARE: Active antitumor treatment
Controlled clinical trial where patients served as their own controls
Symptoms were assessed before chemotherapy at baseline and before each subsequent cycle. Semmes-Weinstein monofilament test (PN, tactile disturbance), thermal simulator to measure thermosensory disturbance (objective symptoms), tuning form to measure vibration perception (objective symptoms), manipulative dexterity to measure performance speed (objective symptom), PROs (Japanese version of the PNQ a validated measure of neuropathy and activities of daily living), cryotherapy tolerability (ad hoc questions), electrophysiological signs (conduction velocity and action potential amplitude of the median nerve), and PKs36
No patients dropped out due to cold intolerance. Pain was reported in 8.2%, and feeling cold was reported in 4.2%. The primary endpoint was tactile deterioration, which was clinically and statistically significantly lower for the intervention side (hand = 27.8% versus 80.6%, OR = 20, p < 0.001; foot = 25% versus 63.9%, OR = infinite, p < 0.001). For secondary endpoints, CIPN occurred faster on the control side than on the intervention side (hand HR = 0.13; foot HR = 0.13). Additional secondary endpoints also reported.
Cryotherapy appears to have efficacy for the prevention of CIPN. In this study, the development of subjective CIPN symptoms was almost completely prevented at a cumulative dose of 960 mg/m2.
Cryotherapy is a promising intervention to prevent CIPN. Additional studies are needed to determine the long-term effects of this therapy on the development of CIPN symptoms in patients treated with paclitaxel.
Fu, X., Wu, H., Li, J., Wang, C., Li, M., Ma, Q., & Yang, W. (2017). Efficacy of drug interventions for chemotherapy-induced chronic peripheral neurotoxicity: A network meta-analysis. Frontiers in Neurology, 8, 223.
STUDY PURPOSE: To evaluate status of research on pharmacologic interventions for CIPN
TYPE OF STUDY: Meta-analysis and systematic review
DATABASES USED: Medline, Embase, and China National Knowledge Internet
YEARS INCLUDED: (Overall for all databases) Information for dates of search not provided, articles included were from 1995 to 2014
INCLUSION CRITERIA: The study (a) assessed CIPN in patients with cancer, (b) compared two or more drugs or placebo, (c) provided sufficient data to assess differences, and (c) assessed incidence or severity of CIPN
EXCLUSION CRITERIA: None listed
TOTAL REFERENCES RETRIEVED: 1,839
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No description of quality evaluation
FINAL NUMBER STUDIES INCLUDED: 23
TOTAL PATIENTS INCLUDED IN REVIEW: 2,298
SAMPLE RANGE ACROSS STUDIES: 20-732
KEY SAMPLE CHARACTERISTICS: All but one of the studies focused on patients getting platinum-based chemotherapy and 12 of 23 only included people with colorectal cancer.
PHASE OF CARE: Active antitumor treatment
Contrary to the title, this article does not include any commonly prescribed prescription drugs, including gabapentin, pregabalin, or duloxetine. This review included studies of amifostine, Vitamin E, calcium and magnesium infusions, and glutathione. Eighteen studies had a placebo control group and had no control group. Neither blinding nor control were needed for inclusion. Findings indicate that Vitamin E and amifostine reduce incidence of CIPN, while glutathione and amifostine reduced severity of CIPN. There was one study (n = 20) included that had patients getting amifostine who all had cervical cancer and were receiving cisplatin with radiation therapy. The authors of this original study (Gallardo et al., 1999) found no statistically significant difference in neurotoxicity between those getting amifostine and those who did not. It is therefore unclear how the authors of the meta-analysis found otherwise. There was also only a single study of glutathione versus placebo versus calcium/magnesium (n = 93, 33 of whom received glutathione) included. The original study (Dong et al., 2010) showed no significant differences in CIPN incidence or severity between the three groups. Four studies of Vitamin E, two which were placebo controlled and two with no control group.
The limitations, including lack of quality control, small sample sizes, focus on platinum use, and GI malignancies, limit the generalizability of the findings from this meta-analysis.
Findings from this study suggest that amifostine, glutathione, and Vitamin E may be helpful for CIPN but no recommendations for practice can be made at this time due to limitations of this meta-analysis.
Bernstein, L.J., McCreath, G.A., Nyhof-Young, J., Dissanayake, D., & Rich, J.B. (2018). A brief psychoeducational intervention improves memory contentment in breast cancer survivors with cognitive concerns: Results of a single-arm prospective study. Supportive Care in Cancer, 26, 2851–2859.
To assess the impact of a brief, individualized, psychoeducational intervention on the self-management of cancer-related cognitive dysfunction (CRCD) for survivors of breast cancer. Primary endpoint: memory contentment; secondary endpoints: knowledge, attitudes, and behaviors related to CRCD.
Participants received a one-hour individualized psychoeducational intervention delivered by a clinical neuropsychologist that was tailored specifically to their level of knowledge and specific complaints related to CRCD. Content included information on CRCD, strategies to reduce frustration and normalize the experience, as well as specific strategies to improve memory. Strategies were not practiced during the session; however, participants selected one or two specific goals to regularly practice between assessment timepoints.
PHASE OF CARE: Multiple phases of care
Single-arm, prospective, longitudinal study
Memory contentment improved from T1 to T2 (p < 0.001, Cohen’s d = 0.58) and T1 to T3 (p < 0.001, d = 0.77).
Reliable Change Index (RCI) indicated statistically reliable change for 32% following the intervention. Reliable change was durable at six weeks postintervention for 38%.
Participants’ statistically significant improvement in memory contentment after the intervention remained lower than published norms at six weeks follow-up (p < 0.001, d = -0.93).
Lower baseline memory contentment predicted increased improvement postintervention (T1-T2: b = -0.18, p = 0.004; T1-T3: b = -0.18, p = -0.023). Change in memory contentment from baseline to six weeks postintervention was positively associated with compensatory strategy effectiveness (b = 3.73, p = 0.011).
The researchers concluded that the brief one-hour, individualized psychoeducational intervention appeared to be effective and durable in relieving distress from CRCD and improving memory contentment and self-efficacy for managing CRCD. They also concluded that the results supported generalizability of the intervention effectiveness to survivors currently on treatment.
Individually tailored psychoeducational interventions for CRCD may be efficacious for facilitating self-efficacy in coping strategies and improvement of memory contentment for survivors of breast cancer. Future study with a randomized controlled design is needed for further validation and investigation of the intervention.
Myers, J.S., Erickson, K.I., Sereika, S.M., & Bender, C.M. (2018). Exercise as an intervention to mitigate decreased cognitive function from cancer and cancer treatment: An integrative review. Cancer Nursing, 41, 327–343.
STUDY PURPOSE: To determine the effectiveness of exercise for minimizing cognitive impairment related to cancer and/or cancer-treatment.
TYPE OF STUDY: Systematic integrative review
DATABASES USED: PsycINFO, PubMed, CINAHL
YEARS INCLUDED: (Overall for all databases) though January 2016
INCLUSION CRITERIA: Quantitative studies evaluating effectiveness of exercise for maintaining cognitive functioning in adult patients with cancer with objective and/or subjective assessments
EXCLUSION CRITERIA: Studies published in a language other than English.
TOTAL REFERENCES RETRIEVED: 232 citations screened, but only 26 met study eligibility criteria.
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Grading of Recommendations Assessment, Development and Evaluating tool was used to appraise the quality of evidence for study outcomes.
FINAL NUMBER STUDIES INCLUDED: 26
TOTAL PATIENTS INCLUDED IN REVIEW: 2,145
SAMPLE RANGE ACROSS STUDIES: 4 to 658 participants.
KEY SAMPLE CHARACTERISTICS: 85% of studies included breast cancer survivors, 77% of all participants received chemotherapy and 31% received radiation therapy.
PHASE OF CARE: Late effects and survivorship
Twenty-six studies evaluated the effectiveness of exercise on improving various cognitive functions (CF) (i.e., memory [M], attention/concentration [AC], executive function [EF], information processing speed [IPS], language [L]) or perceived cognitive function (PCF). Forty-two percent of the studies were randomized controlled trials (n = 11), 42% were quasiexperimental (n = 11), 11.5% were observational (n = 3), and one case study. Interventions included aerobic exercise (n = 4), resistance exercise (n = 3), combination of aerobic and resistance exercise (n = 7), aerobic exercise with another modality (e.g., methylphenidate, psycho-education, behavioral intervention) (n = 4), and mindfulness-based exercise (i.e., yoga, Tai chi, Qigong) (n = 8). Of note, 15% of studies did not have an intervention but, rather, relied on patient self-report regarding exercise.
Eighty-one percent of studies used subjective measures, but only 35% included objective measures of CF. In addition, there was a great deal of variability between instruments used as well the frequency or timing of evaluation. Eighty-eight percent of studies were longitudinal and assessed patients at baseline until less than three months (26%), three months (52%), or six months (22%). While some studies found significant improvements in PCF and/or various cognitive domains (e.g., IPS, AC, EF, L, M), these results were not consistent across studies.
Findings from this study revealed that there is insufficient good quality evidence to determine whether exercise may improve cognitive functioning in cancer survivors. Although exercise may be beneficial in improving cognitive functioning, there is insufficient evidence to determine the type of exercise, including duration and frequency, that would be recommended. Additional research, including multi-site studies with large sample sizes and higher quality evidence, are needed to determine the effectiveness that specific types of exercise might have a role in alleviating cognitive impairment.
Study findings do not support recommending exercise for improving cognitive impairment in cancer survivors. However additional research using these interventions are recommended to further determine their effectiveness.
Larkey, L.K., Roe, D.J., Smith, L., & Millstine, D. (2016). Exploratory outcome assessment of Qigong/Tai Chi Easy on breast cancer survivors. Complementary Therapies in Medicine, 29, 196–203.
Explore whether meditative movement improves cognitive function, quality of life, physical activity, and body mass index (BMI) in postmenopausal women with breast cancer who report clinically significant fatigue.
The intervention included two groups: meditative movement (consisting of Qigong and Tai Chi Easy movements) versus sham Qigong (consisting of similar movements without meditative components), both of which were referred to as rejuvenating movement to blind participants. Participants completed 14 one-hour sessions over 12 weeks with interventionists and were asked to complete 30-minute DVD-guided sessions at home five days per week. Study assessments were done before groups began, at the end of the groups (i.e., 12 weeks post-baseline), and three months after the groups ended.
PHASE OF CARE: Late effects and survivorship
Double-blind randomized controlled trial of meditative movement versus sham control with repeated measures
Feasibility: 86% completed the study, adherence to intervention sessions and home practice not reported; no adverse events
Cognitive impairment: No group differences at baseline. Both groups improved in self-reported cognitive function and attention/working memory tests (time effects, p < 0.05), but no differences were found between the groups (no group by time effect).
Other outcomes: No group differences at baseline. BMI decreased in the meditative movement group but increased in the sham control group (p = 0.0048). All other outcomes showed similar pattern to cognitive impairment (i.e., significant time effects for both groups, but no group by time effects).
This exploratory pilot study suggests that meditative movement does not improve cognitive function more than gentle movement without mindfulness. Although both types of movement may improve cognitive impairment, it is unclear if improvement was due simply to participating in groups.
Study findings do not support suggesting meditative movement exercises such as Qigong or Tai Chi over other types of gentle physical activity to improve cognitive impairment reported by postmenopausal women with breast cancer. The findings do support future well-powered studies using these types of interventions.
Bray, V.J., Dhillon, H.M., Bell, M.L., Kabourakis, M., Fiero, M.H., Yip, D., . . . Vardy, J.L. (2017). Evaluation of a web-based cognitive rehabilitation program in cancer survivors reporting cognitive symptoms after chemotherapy. Journal of Clinical Oncology, 35, 217–225.
The purpose was to compare results of a cognitive rehabilitation program to standard care in patients reporting cognitive symptoms.
All subjects participated in a 30-minute telephone consultation outlining cognitive compensatory strategies prior to study group assignment. Patients were randomly assigned to intervention and control groups. The intervention was a computerized neurocognitive program targeting visual precision, divided attention, working memory, and visual processing speed, which was provided as a CD. Patients were to use training for four 40-minute sessions per week for 15 weeks. The program had an automated measure of compliance. Study assessments were completed by patients at baseline, after 15 weeks, and 6 months later.
PHASE OF CARE: Late effects and survivorship
Longitudinal randomized clinical trial
Only 86% of those in the intervention group used the program. Average total training time was 25 hours of the recommended 40 hours. Patients in the intervention group had better outcomes on the FACT-Cog compared to controls at 15 weeks on all subscales with better perceived cognitive abilities (p < 0.001), less perceived cognitive impairment (p < 0.001) with less impact on quality of life (p = 0.02), and less comments from others regarding cognitive functioning (p = 0.04). However, these differences were sustained at six months only for perceived cognitive impairment (p = 0.001) and perceived cognitive abilities (p < 0.001) but not for the other subscales. Similarly, those in the intervention group had less anxiety and depression (p = 0.02), fatigue (p = 0.03), and perceived stress (p = 0.03) at 15 months. Differences remained only for perceived stress (p = 0.01) at six months. There were no differences between groups in Cogstate measures of neuropsychological function. There was no evidence of dose response for training time and patient outcomes.
The computerized cognitive rehabilitation program tested here showed benefit in terms of patient-reported outcomes of cognitive function but no effect on objective measures of neuropsychological function. There were short-term improvements in anxiety, depression, and fatigue with the intervention that were not sustained.
Findings suggest that computerized cognitive rehabilitation may improve patient perceptions of cognitive functioning; however, these findings were not consistent with objective measures. Actual benefit of computerized cognitive training for cancer treatment-related cognitive impairment remains unclear.