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.
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.