To assess the effectiveness of a combination of Ayurvedic drugs in alleviating cancer- and treatment-related symptoms

Patients initially were divided into two groups. Group 1 did not receive any Ayurvedic drugs. Patients in group 2 received Ayurvedic herbal combinations at various time points during chemotherapy. Within group 2, arm 1 received the same drugs and a full course of chemotherapy while arm 2 received the same drugs at the start of the sixth chemotherapy cycle and arm 3 received them after completing the sixth cycle. Treatment was continued for 16 weeks. Drugs used were maukitkyukta kamdudha (MKD) and mauktikyukta praval panchamruta (MPP) in all treatment arms. Arm 3 also received suvarnabhasmadi (SBD) according to clinician preference based on Eastern Cooperative Oncology Group scores. MKD and MPP at 250 mg each were given orally twice daily. SBD was given orally at a dose of 395 mg twice daily in cow’s ghee. Patients were followed for six months. Outcomes were measured after the first cycle of chemotherapy, after the sixth cycle of chemotherapy, and one month after the sixth cycle.

• N = 64
• AGE: Not provided
• MALES (%): Not provided, FEMALES (%): Not provided
• KEY DISEASE CHARACTERISTICS: Patients with various tumor types receiving different chemotherapy agents including highly emetogenic agents
• OTHER KEY SAMPLE CHARACTERISTICS: None were receiving radiation therapy 

• SITE: Single site 
• SETTING TYPE: Not specified
• LOCATION: India

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

Prospective study

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
• Eastern Cooperative Oncology Group (ECOG) score to reflect symptoms such as pain

Patients in arm 1 of the treatment group showed the least symptom severity of all groups. However, there were no statistically significant differences between the groups in any outcome measure. Symptoms declined in all patients after the first chemotherapy cycle. There were no significant differences in other chemotherapy-related toxicities.

This study showed some interesting but insignificant differences in chemotherapy-associated symptoms between patients receiving Ayurvedic drugs throughout chemotherapy, patients receiving the experimental drugs at difference time points, and patients who did not receive any of these drugs. This study's findings did not show that Ayurvedic drugs were effective in reducing symptoms compared to controls overall. This report had numerous design and reporting limitations.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: The report states that patients who were lost to follow-up were not included in the analysis, but it provides no information on those patients or how many there were. There was no ITT analysis. Measurements such as ECOG scores were insufficient as measures of symptom severity. This report does not provide demographic information about participants and those lost to follow-up. Some interventions were at the physician's discretion, and there was no related subgroup analysis. There was no information about any other interventions for symptom management. No information was provided regarding the actual contents of the drugs used.

Little research has been done on the effects of Ayurvedic drug combinations among patients with cancer as a form of complementary and alternative medicine to manage treatment-related symptoms. This study did not demonstrate the efficacy of the particullar combination tested, and the study had several design and reporting flaws. Additional well-designed and clearly reported research for this type of intervention is needed to determine what role, if any, Ayurvedic drugs have for symptom management in cancer care.

The intervention was a 12-minute cancer orientation program video and an orientation booklet. The video provided an overview of the cancer center, a welcome statement, an introduction to the clinic’s philosophy of care, locations of treatment centers, and identified staff members. The orientation booklet provided more detail and information about various resources and services:

• Welcome statement
• Clinic philosophy
• Introduction to the cancer care center
• What is cancer
• Preparing for your visit
• Cancer center resources and services
• Clinical trials
• Frequently asked questions
• Summary
• Glossary of cancer terms
• Telephone numbers

Measurements done at baseline included questionnaires regarding awareness of cancer resources and services, demographic information, and state and trait anxiety. Postintervention questionnaires three weeks later measured awareness, use of and satisfaction with services and resources, and state and trait anxiety. Before their first MD appointment, patients were consented and randomized to one of four arms:

• Arm 1: Class—A facilitator showed the video and provided the booklet in class (n = 6).
• Arm 2: Drop-in—Patients were invited to view the video at their convenience and pick up a booklet, without staff teaching (n = 7).
• Arm 3: Mailed home—An orientation package containing the video and booklet was mailed to patients’ homes, without staff teaching (n = 23).
• Arm 4: Control group—An invitation was mailed with preintervention questionnaires and instructions. No video or booklet was provided. Information provided to patients and caregivers was part of routine care (n = 18).

• The study reported on a sample of 54 newly diagnosed patients with cancer and their caregivers.
• Patients were receiving care at a medical oncology clinic.
• Most participants were Caucasian, male, and married.
• Patients had a variety of cancer types; 30% had lung cancers.

Medical oncology clinic

A randomized controlled trial design was used.

• Profile of Mood States (POMS)
• State-Trait Anxiety Inventory (STAI)
• Three tools created by the authors and pilot tested: (a) Awareness and Use of Resources, (b) Coping, and (c) Understanding of the Cancer Center
• T test and Fisher exact tests
• 10% difference to determine clinical significance

• The class arm and drop-in arm had less than 10 participants, and their results were not reported.
• Analyses of effect size (partial eta squared) were conducted to further determine the magnitude of associations rather than only relying on null hypothesis significance testing.
• Exact p values reported: The mailed intervention arm was successful in improving patient outcomes, which was most helpful with high trait anxiety (p = 0.005). Baseline state anxiety of the mail arm was p = 0.003, with follow-up of p = 0.18. Baseline state anxiety of the control group was p = 0.02, with follow-up of p = 0.005.
• Fewer benefits for caregivers were noted.

The study had a small sample size.

STUDY PURPOSE: To evaluate the safety and effectiveness of adjunctive or alternative agents to platelet transfusions in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation to prevent bleeding

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 10 trials
• TOTAL PATIENTS INCLUDED IN REVIEW = 554
• SAMPLE RANGE ACROSS STUDIES: Sample size ranged from 18 to 120.
• KEY SAMPLE CHARACTERISTICS: Six trials (n = 336) included patients with acute myeloid leukemia (AML) receiving intensive chemotherapy; two trials (n = 38) included patients with lymphoma undergoing chemotherapy; two trials (n = 180) included participants undergoing allogeneic stem cell transplantation. In nine trials, a thrombopoetin (TPO) mimetic was compared to placebo or standard of care; in one trial, platelet-poor plasma was compared to platelet transfusion. All trials were conducted in high-income countries, and were equally well represented by men and women.

PHASE OF CARE: Active antitumor treatment

The authors concluded that the available evidence does not allow a determination of the effect of TPO or platelet-poor plasma on the prevention of bleeding in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation. This conclusion is attributed to the quality of evidence (very low quality) and the lack of adequate power to detect a clinically significant decrease in bleeding. No trials identified which evaluated agents, such as artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII, or desmopressin, in this population.

Sufficient, high quality evidence does not exist with which to determine the safety or efficacy of adjunctive or alternative agents to platelet transfusions in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation in the prevention of bleeding.

• Mostly low quality/high risk of bias studies
• Low sample sizes
• Studies were underpowered to detect a clinically significant difference in bleeding; in addition, eight trials were funded by the manufacturer of the agent being studied.

Additional studies are needed to evaluate adjunctive or alternative agents in the prevention of bleeding. Neither TPO nor plasma-poor platelets can be substituted for platelet transfusions given the current state of knowledge.

• RESOURCE TYPE: Evidence-based guideline

• PHASE OF CARE: Active antitumor treatment

No information is provided regarding the volume of evidence retrieved or quality ratings of studies included.

• Oral hygiene
• Pretreatment control of preexisting periodontal and dental disease with professional cleaning
• Routine use of palifermin is not recommended.

• Regular oral care with use of nonalcohol-containing mouthwashes
• At least weekly assessment

All specific interventions had either recommendations against use or no ability to provide a recommendation. Cryotherapy even with bolus 5-FU was not recommended due to lack of evidence in the setting of RT for patients with head and neck cancer. The guideline provides a listing of numerous interventions that have been examined with no recommendations for use.

• Limited search and no clear study quality rating
• Unclear if the panel reviewed all the evidence or just statements created by an individual facilitator

This review provides a comprehensive list of interventions, none of which can be recommended for practice. This article does provide a good overview of assessment instruments and provides some information on probable risk factors.

To determine the effects of yoga on self-reported cognitive function

Certified yoga instructors led two 90-minute yoga group classes per week for 12 weeks. Each group contained 4–20 participants. Hatha yoga poses targeting relaxation, mindful breathing, chest opening, spinal extension, upper-body strength, and mobility were predetermined for each of the 24 sessions, and protocol drift was monitored. Pamphlets describing the poses from the classes and a yoga DVD were provided for home practice. Participants recorded weekly home and class time to determine dose effects. Participants who missed a class were called to improve adherence. Waitlist control participants continued regular activities and were directed not to begin yoga practice until after their final assessments. Measures were assessed before the behavioral intervention, immediately after the 12-week intervention, and three months after the intervention.

• N = 200  
• MEAN AGE = 51.6 years (SD = 9.2 years) 
• FEMALES (%): 100
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors in stages 0-IIIA between two months and three years after the completion of primary and adjuvant treatment (except for antiestrogen therapy).
• OTHER KEY SAMPLE CHARACTERISTICS: The sample was an average of 17.3 (SD = 8.1) months since diagnosis and 10.9 ( SD = 7.9) months since treatment. The sample was highly educated; 69.5% of participants were college graduates or had postgraduate education. 81% of participants were postmenopausal.

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Ohio State University Cancer Center in Columbus, Ohio, a yoga studio, and participants’ homes

• PHASE OF CARE: Late effects and survivorship

Randomized, waitlist-controlled trial

• Breast Cancer Prevention Trial (BCPT) Symptom Checklist–Cognitive Problems subscale
• Center for Epidemiological Studies–Depression (CES-D) scale
• Beck Anxiety Inventory (BAI)
• Pittsburgh Sleep Quality Index (PSQI)
• Medical Outcomes Study Short-Form survey (SF-36) Energy Subscale
• Community Healthy Activities Model Program for Seniors questionnaire (CHAMPS) (physical activity)
• Fasting blood samples for lipopolysaccharide-stimulated cytokine levels (IL-6, IL-1 beta, TNF-alpha)

At baseline, the average self-reported cognitive impairment was slight to moderate and did not differ between groups. Overall group and group-by-time effects were found (p < .05, both). Although no differences were found immediately after the 12-week intervention, the intervention group reported significantly less cognitive impairment than controls three months after the intervention ended (p < .01). However, these effects did not remain after controlling for symptom covariates (e.g., anxiety, depression, fatigue, sleep quality). Participants with more daily yoga practice (mean of 29 minutes) reported less cognitive impairment postintervention through three months (p = .011), and participants with less daily yoga practice (mean of 18 minutes) or no daily yoga practice did not report these changes. This dose response remained when controlling for symptom covariates. At three months, the intervention group reported more physical activity than controls (p = .032). Cytokine levels did not predict changes in self-reported cognitive impairment.

A 12-week, group Hatha yoga intervention provided by a trained instructor may improve self-reported cognitive impairment in breast cancer survivors. This effect may be mediated by improvements in co-occurring symptoms. Practicing yoga for at least 30 minutes per day may be required for a significant improvement over time in cognitive impairment.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Participants were not blinded to their group assignment. The nonspecific effects of social support or attention may have been responsible for improvements in symptoms given the lack of a control group. It was unknown what component of the intervention (e.g., physical activity, mindfulness) was active. The sample was mostly white and well-educated, limiting generalizability. The intervention would require training for facilitators to maintain fidelity. Cognitive function was measured only with self-report instruments. The duration of the intervention effect is unknown because of the lack of long-term (> 3 months) follow-up assessments.

A group Hatha yoga class delivered by a trained facilitator may improve cognitive impairment for breast cancer survivors. However, more research with a longer follow-up period is warranted to determine whether the intervention is effective, what component of the intervention is active, and whether yoga is practical for implementation in practice.

To investigate whether nurse monitoring and protocol management of physical symptoms alleviates fatigue

Patients were randomized to receive either usual care or nurse management patient-tailored treatment using treatment management protocols. In the experimental group, nurse specialists recorded interventions for multiple physical symptoms. During outpatient meetings with the nurse, symptom severity was monitored. When any symptoms were rated ≥ 4 on an 11-point scale, the nurse referred the patient to the oncologist for further assessment and initiation of treatment according to palliative care guidelines, such as medication adjustment, other referrals, or other interventions. Nurses managed as many symptoms independently as possible. Highly specific interventions for pain, nausea, vomiting, constipation, diarrhea, anorexia, dyspnea, cough, and dry mouth were used. No specific interventions aimed at fatigue were identified. Patients met with the nurse at 1, 2–4, 5–7, and 8–10 weeks. Study assessments were done via mail at baseline and one, two, and three months.

• The study reported on a sample of 137 patients.
• Mean patient age was 58 years.
• The sample was 59% female and 41% male.
• Multiple solid tumor types were represented, with breast, gastrointestinal, and urogenital being the most common.
• Seventy-eight percent of patients were married or living with a partner, with more intervention group patients in this group.
• All patients were Caucasian.
• Average time since cancer diagnosis was 57 months.
• Patients were not eligible if they had a level of anxiety or depression requiring referral for psychiatric care or cognitive impairment.

• Single site
• Outpatient setting
• The Netherlands

A randomized controlled trial design was used.

• Numeric rating scale (NRS) to assess symptoms on 0–10 scale
• Multidimensional Fatigue Inventory (MFI)
• EORTC Quality of Life Questionnaire (QLC-30)
• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)

Patients reported that the most troublesome symptoms were pain, dyspnea, and anorexia. Patients had a median of two symptoms with NRS scores of at least 4 at baseline. MFI scores for general fatigue declined significantly over time in the intervention group compared to controls, with effect size ranging from 0.26 to 0.35 (p = 0.01). NRS fatigue scores also demonstrated decline compared to usual care controls (p < 0.001). BFI scores were not reported. Overall symptom burden was reported to decrease over time in the intervention group, while there was no change in controls (maximal effect size = 0.64, p = 0.002). Anxiety decreased in the intervention group compared to controls (maximal effect size = 0.32, p < 0.001).

Findings suggest that comprehensive management and monitoring for symptom control by nurse specialists was effective in reducing anxiety and fatigue in patients with cancer.

• The study had baseline sample/group differences of import.
• The study had risk of bias due to no blinding and no appropriate attentional control condition.
• Unintended interventions or applicable interventions were not described that would influence results.
• The study used selective outcomes reporting.
• Measurement/methods were not well described.
• Participant withdrawals were ≥ 10%.
• At baseline, fewer control patients were married or partnered, and there was no analysis of significance of baseline differences. This support difference could have influenced results.
• BFI measures were not reported, causing one to question if findings were not consistent for changes in fatigue.
• Calculation of “total symptom burden” was not described.
• Patients who withdrew were more anxious and depressed than those who remained in the study.

Findings suggest that continued symptom management and monitoring with a protocol approach can be effective for reducing symptoms overall, and reducing fatigue and anxiety. There were no specific intervention approaches identified that were used for fatigue, so the suggestion is that reducing other symptoms can have a positive impact on fatigue. There were also no specific interventions identified for anxiety, but anxiety also declined over time. These results suggest that ongoing monitoring and attention to patients alone may positively impact these symptoms.

To evaluate the efficacy of doxycycline in the prevention of erlotinib-induced rash (folliculitis) in patients with non-small cell lung cancer (NSCLC)

Patients were randomized via a computer website to receive either erlotinib 150 mg/d per os or erlotinib 150 mg/d per os plus 100 mg/d of doxycycline. Doxycycline began on day 0 (day of randomization) and was continued for four months and as long as 12 months at the primary investigator's discretion. Erlotinib began on day 1 and was administered for as long as 12 months or beyond or until disease progression or intolerable toxicity. Patients were evaluated on days 14 and 28 and at months 2, 4, 7, 10, and 12. Patients with grade 2 or higher folliculitis received treatment as appropriate.

• N = 147   
• MEAN AGE = 64 years (SD = 11)
• MALES: 67%, FEMALES: 33% 
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Patients with NSCLC 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients being treated with erlotinib, patients aged 18 years or older, patients with histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC, patients who had failed first-line platinum-based chemotherapy, measurable disease was according to response Evaluation Criteria in Solid Tumors, patients who had an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2 (e.g., scale from 0 [fully active] to 4 [completely disabled]), patients who had adequate organ function and an estimated life expectancy of 12 weeks or longer

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Lausanne, Switzerland, and 23 sites in France

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

Open-label, randomized, prospective, phase II trial

• Skin efficacy—anonymous photographs were analyzed by a committee of blinded expert dermatologist using Common Terminology Criteria for Adverse Events (CTCAE) grading.
• Tumor response—Response Evaluation Criteria in Solid Tumors (RECIST)
• Quality of life—Dermatology Life Quality Index (DLQI)
• Compliance—daily doses of erlotinib and doxycycline were collected at each study time point.
• Adverse events—graded according to CTCAE, version 3.0

FOLLICULITIS: During the first four months of treatment, 52 patients (71%) in the doxycycline arm and 59 patients (81%) in the control arm developed folliculitis (p = 0.18). The mean duration of folliculitis was similar in both treatment arms (no p value given). Sixty-two percent of patients in the intervention arm developed grade 1 folliculitis compared to 19% in the control arm. Grade 3 folliculitis developed in 4% of patients in the intervention arm and 19% in the control arm (p < 0.001).

Doxycycline did not reduce the incidence of erlotinib-induced folliculitis but significantly reduced its severity. In fact, more patients in the intervention arm developed grade 1 folliculitis compared to the control arm. The duration of folliculitis was similar in both the intervention and control arm in this study. Compliance with erlotinib was higher in the doxycycline arm during the whole treatment period.

• Risk of bias (sample characteristics)
• Risk of bias (due to open label)
• More males than females in study
• The authors did not report on possible statistical differences in sample characteristics.

Nurses can collaborate with physicians to verify that doxycycline is combined with erlotinib treatment to improve the level of toxicity of folliculitis. Doxycycline has the potential to decrease the severity of folliculitis in patients with NSCLC who are receiving erlotinib. It does not, however, reduce the incidence of folliculitis in these patients during the first four months of treatment with erlotinib, nor does it reduce the duration of folliculitis.

STUDY PURPOSE: To evaluate if a dose response effect of exercise on inflammation and fatigue in cancer survivors exists

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED =  31 included in meta-regression 
• TOTAL PATIENTS INCLUDED IN REVIEW = 3,816
• SAMPLE RANGE ACROSS STUDIES: 16–500
• KEY SAMPLE CHARACTERISTICS: Participants had various tumor types, and the study included individuals in and post active treatment with chemotherapy and/or radiotherapy and/or surgery.

PHASE OF CARE: Multiple phases of care

Exercise interventions included aerobic, resistance, flexibility, and combinations of these. Interventions included supervised, unsupervised, home-based, hospital- or other setting–based, and group or individual exercise sessions. Moderate quality evidence that exercise had a positive effect on fatigue compared to usual care existed (standard mean deviation = 0.32, 95% confidence interval [0.13, 0.52]). A combination of aerobic and resistance provided the largest treatment effect. Aerobic intensity was negatively related to treatment effect. No relationships existed between resistance exercise and treatment effect.

Exercise has a beneficial effect on fatigue. Moderate intensity exercise appears to be most beneficial.

Varied study quality and sample sizes

This analysis adds to the body of evidence that exercise has a beneficial effect on fatigue among patients with cancer. This study suggests that moderate level aerobic exercise is more beneficial than more intense exercise. This information can be used to guide patient counseling and teaching to incorporate moderate exercise into daily routines.

A uniform NCCN consensus determined that recommendations were appropriate (NCCN Category of Evidence and Consensus = 2A).

Some interventions that may be useful to improve or maintain cognitive function might not be included in these guidelines because this manuscript did not detail search strategies, inclusions and exclusions, or the number of articles included in the recommendations.

The NCCN cognitive function algorithm aids healthcare professionals considering the assessment and treatment of cancer-related cognitive function. Nonpharmacologic interventions should be recommended to oncology survivors experiencing cognitive issues. Pharmacologic interventions may be considered when medical conditions permit and potential contributing factors are ruled out or managed.

STUDY PURPOSE: To conduct a systematic review of the research evidence for the effects of Radix Astragali (RA)–based Chinese herbal medicine in the prevention and treatment of oxaliplatin-induced peripheral neuropathy (PN)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 24 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,552
• SAMPLE RANGE ACROSS STUDIES: 40–135; average size = 66
• KEY SAMPLE CHARACTERISTICS: 11 trials inpatients (n = 689); no setting identified for the other 13 trials (n = 863); 24 trials = 58.63% were male; colorectal cancer (n = 1,033); gastric cancer (n = 399); lung/breast/other cancers (n = 52), not specified (n = 68); range for total OXALI dose in all studies = 130 mg/m²–800 mg/m²; range for total OXALI dose in 11 trials 260–600 mg/m²

PHASE OF CARE: Not specified or not applicable; cannot determine if studies were in palliative care setting

APPLICATIONS: Elder care

• Fifteen RCTs comparing RA-based combined remedies to no intervention significantly reduced CIPN occurrence (n = 993 patients, odds ratio [OR] = 0.19, 95% CI confidence interval [0.14, 0.25], p < 0.01).
• One RCT comparing RA-based prescription to mecobalamin reduced CIPN occurrence (n = 42 patients, OR = 0.17, 95% CI [0.03, 0.94], p < 0.05).
• Two RCTs comparing RA-based prescription in addition to reduced glutathione versus calcium/magnesium infusions with the same conventional medications reduced CIPN occurrence (n = 120 patients, OR = 0.42, 95% CI [0.18, 0.97], p < 0.05).
• Fourteen RCTs comparing RA-based intervention versus no intervention significantly reduced the incidence of high-grade PN (11 trials used Levi’s grading) (n = 931 patients, OR = 0.17, 95% CI [0.09, 0.31], p < 0.01). No significant difference was found in the two trials comparing RA to mecobalamin or the two trials comparing RA to reduced glutathione or calcium/magnesium infusion with the same conventional medications. 
• Three RCTs comparing RA-based prescriptions and mecobalamin to mecobalamin alone found significant effect for RA-based prescription and mecobalamin in relieving CIPN (n = 213 patients, OR = 4.84, 95% CI [2.38, 9.83], p < 0.01).
• Six RCTs reported that the TA-based intervention significantly improved sensory nerve conduction velocity (MD = 4.42 m/s, 95% CI [3.27, 5.57], p < 0.01). No difference existed in motor nerve conduction velocity.
• No adverse events were reported in the 24 included studies for RA-based interventions. No consistent data was reported for quality of life, with only two trials including quality of life improvement after RA-based interventions.
• Funnel plots did not indicate publication bias.
• Effect sizes were not reported.

This meta-analysis indicated that RA-based interventions may provide potential benefit for oxaliplatin-induced PN. Although this meta-analysis did not show significant heterogeneity for different trial results, it did show considerable heterogeneity in the variables, treatments, and outcome measures studied. Studies included RA-based interventions with no reliable measures of drug composition, varied drug doses, self-made drug preparations, or RA combined with herbal compositions with variation in drug delivery methods. Therefore, it is premature to interpret these results as beneficial because of the substantial limitations for reliability and validity of the study results.

• Limited search
• High heterogeneity
• Low sample sizes
• Predominant yield of studies from only two databases: CNKI and Wanfang
• Safety, adverse event, or quality of life not used in search terms
• Twenty-four RCTs included three different CIPN grading scales.
• More than 50% of RA-based prescriptions included other herbal substances.
• No consistent reliable measure of drug composition
• Ten of the 24 RCTs had self-made prescriptions.
• Different RCT comparators (i.e., intervention, no intervention)
• More RCTs comparing RA-based prescription versus no intervention
• Doses/administration/duration of RA treatment different (oral = 10 RCTs, topical = 12 RCTs, IV = 1 RCT)
• Unclear phase of care or previous neurotoxic chemotherapy exposures
• Differences in duration of chemotherapy exposures and accumulated OXALI doses
• No multicenter large scale trials
• Effect sizes were not reported.

It remains unclear if RA provides benefit in alleviating oxaliplatin-induced PN. Additional RCTs are required to evaluate the reliable preparations of RA to investigate its full effects isolated in simple form versus its combined effect with other herbs. The effect of RA on the antitumor activity of oxaliplatin or other chemotherapeutic agents needs further study. Large multisite RCTs are needed to further evaluate drug safety in all phases of treatment and to identify the most effective dose, delivery method, duration of treatment, and quality of life.