Chemotherapy-induced Peripheral Neuropathy In Patients Research Articles

Acupuncture combined with methylcobalamin for the treatment of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) seriously affects the quality of life of patients with multiple myeloma (MM) as well as the response rate to chemotherapy. Acupuncture has a potential role in the treatment of CIPN, but at present there have been no randomized clinical research studies to analyze the effectiveness of acupuncture for the treatment of CIPN, particularly in MM patients.MethodsThe MM patients (104 individuals) who met the inclusion criteria were randomly assigned into a solely methylcobalamin therapy group (500 μg intramuscular methylcobalamin injections every other day for 20 days; ten injections) followed by 2 months of 500 μg oral methylcobalamin administration, three times per day) and an acupuncture combined with methylcobalamin (Met + Acu) group (methylcobalamin used the same way as above accompanied by three cycles of acupuncture). Of the patients, 98 out of 104 completed the treatment and follow-ups. There were 49 patients in each group. The evaluating parameters included the visual analogue scale (VAS) pain score, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire scores, and electromyographic (EMG) nerve conduction velocity (NCV) determinations. We evaluated the changes of the parameters in each group before and after the therapies and made a comparison between the two groups.ResultsAfter 84 days (three cycles) of therapy, the pain was significantly alleviated in both groups, with a significantly higher decrease in the acupuncture treated group (P < 0.01). The patients’ daily activity evaluated by Fact/GOG-Ntx questionnaires significantly improved in the Met + Acu group (P < 0.001). The NCV in the Met + Acu group improved significantly while amelioration in the control group was not observed.ConclusionsThe present study suggests that acupuncture combined with methylcobalamin in the treatment of CIPN showed a better outcome than methylcobalamin administration alone.Trial registrationChina Clinical Trials Register (registration no. ChiCTR-INR-16009079, registration date August 24, 2016).

Effect of the CEP72 Genotype and CYP3A5-Mediated Metabolism in Predicting Vincristine-Associated Peripheral Neuropathy

Introduction:Chemotherapy induced peripheral neuropathy (CIPN) is a recognized clinical outcome of vinca alkaloid based therapy that frequently results in dose reduction or therapy discontinuation, but the determinants of interpatient variability remain unpredictable.Previous pharmacogenetics studies have demonstrated that vincristine is metabolized through the CYP3A system with the CYP3A5*3 variant (GG allele at rs776746) having the least efficacy in metabolizing vincristine to its inactive metabolite M1 and conferring higher risk of neurotoxicity. Similarly, a single nucleotide polymorphism (SNP) in the promoter of the CEP72 gene (TT allele at rs924607) has been described as being significantly associated with increased risk and severity of vincristine-associated peripheral neuropathy in the pediatric population. Our recent studies have further studied the incidence of this risk allele and its correspondence with CIPN in the adult population treated with vincristine. This study aimed to investigate if an additive SNP analysis, both for CYP3A5*3 and CEP72, would determine increased predictability of CIPN in patients treated with vinca alkaloids.Methods:A retrospective case-control study of patients was completed in patients that were exposed to vinca alkaloids (vincristine, vinorelbine, and vinblastine) at Geisinger Medical Center from 2007-2015. Available samples of these patients were identified in the Geisinger MyCode bio banking project and the SNP of interest was genotyped using the TaqMan® SNP Genotyping Assay, with genotypic discrimination performed using SDS software (Applied Biosystems). Cases of CIPN were confirmed with retrospective chart review. Statistical analysis was conducted using SAS (SAS Institute Inc.) software, version 9.4. All genotyping and chart review was conducted by personnel blinded to sample identity.Results:A total of 121 patients had genotype mapping completed, of which 60 patients received vincristine, 33 received vinblastine, and 28 received vinorelbine. CIPN was detected in 35.5% of the study population. The CEP72 risk allele (TT) was detected in 14.9% (n=18) of the cohort and the CYP3A5*3 risk allele (GG) was detected in 89.2% (n=108) of the cohort, with similar incidence in each drug class. The median age of this population was 61 years of age with 52.9% (n=64) being males.Multivariate logistic regression analysis, controlling for age and sex, did not demonstrate a significant model for the recessive genetic model of both SNPs with all vinca alkaloids (p=0.33), vincristine alone (p=0.26), vinorelbine alone (p=0.98), or vinblastine alone (p=0.97). The incidence of the inactive G/G allele for CYP3A5*3 was seen in 87.5% (n=21) of the vincristine cohort with neuropathy,The incidence of neuropathy was higher in patients with the TT genotype (75%) in patients receiving vincristine therapy than with the CT or CC genotype (35.7%). As consistent with prior findings, a similar dominant effect was not detected in vinorelbine or vinblastine groups. In the vincristine population (n=60), diseases that were treated included diffuse large B-cell lymphoma (n=29), acute lymphoblastic leukemia (n=6), oligoastrocytoma (n=5), and Ewing's sarcoma (n=2). No disease specific variation in neuropathy incidence and association with TT genotype was detected. Patients received a median three doses of vincristine at 2 mg each (total 6 mg) before detection of CIPN. Four patients (6.67%) of the patients required dose adjustment of chemotherapy, including dose reduction (n=2) or early discontinuation (n=2).Conclusions:This study demonstrates that the CEP72 genotype confers predictive modeling for patients receiving vincristine-based therapy and that including CYP3A5*3 analysis in an additive model is not associated with an increased predictive model for CIPN in patients receiving vinca alkaloid based therapy. In our population, the high incidence of the inactive G/G allele of CYP3A5*3 made it difficult to discern a significant effect in patients that experienced neuropathy. Larger studies are needed to include a more diverse population to confirm this predictive association and to understand if this can help guide precision-based chemotherapy administration and favorably impact disease prognosis. DisclosuresNo relevant conflicts of interest to declare.

Characteristics of chemotherapy-induced peripheral neuropathy in patients with breast cancer.

85 Background: In Brazil, breast cancer has the second highest incidence of neoplasms, the most common among women. It is expected there will be 57,120 new cases and a risk 56.09 cases per 100 thousand women. For its treatment, neurotoxic chemotherapeutics that can cause chemotherapy-induced peripheral neuropathy (CIPN) are used. Methods: This is an exploratory descriptive study developed in a cancer treatment reference hospital in the city of Sao Paulo, Brazil. Aim: To search the patients with breast cancer during treatment with neurotoxic agents and evaluate the presence of CIPN with application of Chemotherapy-Induced Peripheral Neuropathy Assessment Tool questionnaire (CIPNAT). Results: The sample was 44 women with a mean age of 52 years (SD = 10.54), 47.7% had local disease, 72.7% were treating with taxanes neurotoxic agents. The main neuropathic symptoms measured at CIPNAT: 75% had motor symptom weakness with an average score for severity of 6.45 causing an average of distress 5.36; 65.9% muscle and joint pain average severity of 6.31 causing an average of 5.59 distress; and 56.8% sensitive symptom numbness in the hands average severity of 4.76 causing an average of 3.52 distress. These symptoms had a negative impact in the activities of daily living (ADL) such as physical exercise (mean score = 5.32), enjoyment of life (mean score = 4.77) and leisure activities (mean score = 4, 03). Although few (13.6%) reported that suffered some injury or accident due to CIPN. Discussion: The results are consistent with those presented in the scientific literature, but measured with other assessment tools such as the NCI CTCAE, WHO and EORTC QLQ-C30 and CIPN20, which also showed that motor disorders (weakness, muscle cramps and loss of strength in the hands) and sensory (numbness and tingling in the hands and feet). Conclusions: The study explores the relationship between CIPN and ADL affected during treatment for breast cancer. Through the motor and sensory symptoms reported by CIPNAT, nursing will have grant to develop educational strategies to prevent and minimize negative impacts on the quality of life of women with breast cancer undergoing treatment with neurotoxic agents.

Assessment of chemotherapy-induced peripheral neuropathy using the LDIFLARE technique: a novel technique to detect neural small fiber dysfunction.

IntroductionThe diagnosis and quantification of chemotherapy-induced peripheral neuropathy (CIPN) remains a challenge. Conventional methods including quantitative sensory testing (QST), nerve conduction tests, and biopsy are unable to detect subclinical changes, and do not consistently correlate with severity of patients' symptoms and functional impairment. This study aims to determine the utility of the LDI (laser Doppler imager) FLARE technique in the diagnosis of CIPN and whether it correlates with symptom severity.Materials and MethodsWe assessed 24 patients with established CIPN [12 due to platinum analogs (PA) and 12 to Taxanes (TX)] and 24 matched healthy controls (HC). All underwent neurophysiological examination including vibration perception threshold (VPT), sural nerve amplitude (SNAP) and conduction velocity (SNCV), LDIFLARE, and fasting biochemistry. The QLQ-CIPN20 questionnaire was used to assess symptom severity.ResultsHC, combined chemotherapy (CG), PA, and TX groups were matched for age, sex, BMI, and blood pressure. The LDIFLARE was significantly reduced in CG compared to HC (P =< 0.0001), whereas SNAP (P = 0.058) and SNCV (P = 0.054) were not. The LDIFLARE correlated with the QLQ-CIPN20 symptom scores in all three categories namely, CG (P =< 0.0001), PA (P = 0.001) and TX (P = 0.027) whilst, VPT, SNAP, and SNCV did not.ConclusionOur findings suggest that the LDIFLARE technique is more helpful in confirming the diagnosis of CIPN in patients with distal sensory symptoms than current commonly used methods. Moreover, this novel test fulfils the unmet need for a diagnostic test that relates to the severity of symptoms. This may be useful in quantifying early changes in small fibre function indicating early CIPN.

Review: Quality of life and resilience related to chemotherapy-induced peripheral neuropathy in patients post treatment with platinums and taxanes

Review of: Egan, M., Burke, E., Meskell, P., MacNeela, P. and Dowling, M. (2015) Quality of life and resilience related to chemotherapy-induced peripheral neuropathy in patients post treatment with platinums and taxanes. Journal of Research in Nursing 20(5), pp. 385-398.

Chemotherapy-induced peripheral neuropathy in the adult

This review focuses on the newest data on mechanistic aspects of chemotherapy-induced peripheral neuropathy (CIPN), its assessment and the current status of neuroprotection and treatment options. Several anticancer drugs are associated with CIPN. Rodent models showed that axons, dorsal root ganglia and terminal trees are affected, whereas myelin remains unaffected. Oxidative stress and mitochondrial damage, as well as the role of nerve growth factor, have been highlighted in CIPN. Candidate genes, single nucleotide polymorphisms, were correlated with a higher incidence of CIPN in patients receiving a combination of chemotherapies. CIPN assessment mainly relies on patient-oriented questionnaires, nevertheless an international effort is ongoing to access reliable and objective means to assess small and large fiber impairment.To date, dose modification is the most effective strategy to prevent CIPN, whereas duloxetine is recommended for patients with painful CIPN. CIPN is a common, potentially severe and dose-limiting adverse effect of cancer treatment. Chemotherapies mainly target axons, dorsal root ganglia and terminal trees of intraepidermal nerve fibers. A quick and noninvasive method allowing the assessment of CIPN should be developed, although no treatment prevents CIPN or improves its long-term course. Furthermore, symptomatic therapy is often largely ineffective in reducing CIPN symptoms.

Chemotherapy induced peripheral neuropathy: the modified total neuropathy score in clinical practice

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, potentially reversible side effect of some chemotherapeutic agents. CIPN is associated with decreased balance, function and quality of life (QoL). This association has to date been under-investigated. To profile patients presenting with CIPN using the modified Total Neuropathy Score (mTNS) in this cross-sectional study and to examine the relationship between CIPN (measured by mTNS) and indices of balance, quality of life (QoL) and function. Patients receiving neurotoxic chemotherapy regimens were identified using hospital databases. Those who did not have a pre-existing neuropathy were invited to complete mTNS, Berg Balance Scale (BBS), timed up and go (TUG), and FACT-G QoL questionnaire. mTNS scores were profiled and also correlated with BBS, TUG and FACT-G using Spearmans correlation coefficient. A total of 29 patients undergoing neurotoxic chemotherapy regimens were tested. The patients mTNS scores ranged between 1 and 12 (median = 5), indicating that all patients had clinical evidence of neuropathy on mTNS. No significant correlations were found between mTNS and BERG (r = -0.29), TUG (r = 0.14), or FACT-G (r = 0.05). This study found a high prevalence of CIPN in patients treated with neurotoxic chemotherapy regimens. The mTNS provided a clinically applicable, sensitive screening tool for CIPN which could prove useful in clinical practice. mTNS did not correlate with BBS, TUG or FACT-G in this sample, possibly due to relatively mild levels of CIPN and consequent subtle impairments which were not adequately captured by gross functional assessments.

Symptom and Interference of Activities of Daily Living of Chemotherapy-Induced Peripheral Neuropathy in Patients Receiving Taxanes and Platinums

Purpose: The purpose of this study was to identify the symptoms and interference of activities of daily living (ADL) of chemotherapy induced peripheral neuropathy (CIPN) in patients receiving taxane and platinums. Methods: 141 cancer patients were recruited in the cross-sectional survey design. The instruments used in the study was the Chemotherapy-induced Peripheral Neuropathy Assessment Tool (CIPNAT) developed by Tofthagen and colleagues. Results: The patients experienced the symptom and interference of ADL of CIPN moderately. The most common symptom was nerve pain (70.2%) and the patients with high cumulative doses showed a significant of tingling sensation in the feet. Symptom severity increased substantially with cumulative dose of chemotherapeutic agents. Conclusion: The results of this study suggest that chemotherapy-induced peripheral neuropathy increase due to repeated chemotherapy and nursing intervention is necessary to reduce symptom severity and interference of ADL of CIPN.

Nurse self-evaluation of assessment of chemotherapy-induced peripheral neuropathy in patients with cancer.

The focus of this study was to assess the feasibility and clinical implementation of a standardized assessment for chemotherapy-induced peripheral neuropathy (CIPN) by registered nurses in patients undergoing neurotoxic chemotherapy. A total of 24 registered nurses from 4 different institutions were enrolled into the study. A pre- and posttest design was used to assess changes in nurses' attitudes, knowledge, and perceived skill in CIPN assessment. Using selected data collection instruments, nurses performed standardized assessments during the course of chemotherapy treatments. Patient-reported symptoms, vibratory sensation, deep-tendon reflexes, and touch were collected at three time points during chemotherapy treatment. Results indicated there was no statistically significant change in knowledge of chemotherapy-induced peripheral neuropathy from baseline to the end of the study. However, this finding may be due to poor internal consistency noted among the items of the Nurse Knowledge and Attitudes CIPN Assessment. Implementation of a standardized subjective and objective nursing assessment of CIPN was feasible with a total mean feasibility score of 3.76 (range 0-5) with each individual item scoring between 3.35 and 3.91. The intervention did improve pretest and posttest confidence in performing assessment for CIPN (p = .003).

1592P - Chemotherapy Induced Peripheral Neuropathy: The Role of the Modified Total Neuropathy Score.

ABSTRACT Background Chemotherapy induced peripheral neuropathy (CIPN) is a common, potentially reversible side-effect of some chemotherapeutic agents. Common toxicity scales used in clinical practice are subjective, insensitive to change, and may underreport this phenomenon. The use of nerve conduction studies is invasive and impractical in routine practice. The modified total neuropathy score (mTNS) provides a comprehensive non-invasive measure of CIPN. CIPN is associated with decreased balance, function and quality of life (QoL). This association has to date been under-investigated. Methods All patients receiving neurotoxic chemotherapy regimes over a seven week period during July / August 2011 were identified using the hospital pharmacy database and once screened for inclusion/exclusion criteria, were invited to complete the mTNS, Berg Balance Scale (BBS), Timed Up and Go (TUG), and the FACT-G QoL questionnaire. mTNS scores were profiled and correlated with BBS, TUG and FACT-G using Spearmans correlation coefficient. All assessments were carried out under the supervision of a Senior Physiotherapist. Results A total of 29 patients undergoing a variety of neurotoxic chemotherapy regimes (taxanes n = 9, vinca-alkaloids n = 3, platinums n = 13, combination platinum/taxane regimes n = 4) were assessed. The patients mTNS scores ranged between 1 and 12 (median score = 5), indicating that all patients had some signs of neuropathy on mTNS, and 93% (n = 27) had scores indicative of CIPN. No significant correlations were found between mTNS and BERG (r = -.289; p = 0.05), TUG (r = .136; p = 0.05), or FACT-G (r = 0.050; p = 0.05). Conclusion This study found a high prevalence of CIPN in patients treated with neurotoxic chemotherapy regimes as assessed by the mTNS. The mTNS provided a clinically applicable, sensitive screening tool for CIPN which could prove useful in clinical practice. mTNS did not correlate with BERG, TUG or FACT-G in this study, which may be due to relatively mild levels of CIPN and consequent subtle impairments which were not adequately captured by gross functional assessments. Disclosure All authors have declared no conflicts of interest.

Statistical identification of predictors for peripheral neuropathy associated with administration of bortezomib, taxanes, oxaliplatin or vincristine using ordered logistic regression analysis

Chemotherapy-induced peripheral neuropathy (CIPN) is a major drug-induced adverse reaction that becomes a dose-limiting toxicity. However, effective strategies for preventing or treating CIPN are lacking. Accordingly, this study aimed to statistically identify predictors for CIPN. Retrospective analysis was carried out for 190 patients who had been treated with bortezomib (n=28), taxanes (paclitaxel or docetaxel; n=58), oxaliplatin (n=52) or vincristine (n=52) at our hospital between April 2005 and December 2008. The severity of CIPN was assessed at the time of chemotherapy completion, graded as grade 0-5 in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Multivariate ordered logistic regression analysis was used to investigate predictors for CIPN. Predictors for CIPN in patients that were administered bortezomib were no co-administration of dexamethasone [odds ratio (OR), 0.455; confidence interval (CI), 0.208-0.955; P=0.0376] and sex (male) (OR, 3.035; CI, 1.356-6.793; P=0.0069). For taxanes (paclitaxel or docetaxel), the predictor for CIPN was a large number of chemotherapy cycles (OR, 2.379; CI, 1.035-5.466; P=0.0412). For oxaliplatin, the predictors for CIPN were a large number of chemotherapy cycles (OR, 3.089; CI, 1.598-5.972; P=0.0008) and no co-administration of non-steroidal anti-inflammatory drugs (OR, 0.393; CI, 0.197-0.785; P=0.0082). For vincristine, predictors for CIPN were a large number of chemotherapy cycles (OR, 6.015; CI, 1.880-19.248; P=0.0025) and co-administration of an analgesic adjuvant (OR, 3.907; CI, 1.383-11.031; P=0.0101). In conclusion, our study indicates that CIPN will be alleviated by the co-administration of dexamethasone with bortezomib and non-steroidal anti-inflammatory drugs with oxaliplatin.

The Reliability and Validity of a Modified Total Neuropathy Score-Reduced and Neuropathic Pain Severity Items When Used to Measure Chemotherapy-Induced Peripheral Neuropathy in Patients Receiving Taxanes and Platinums

Assessment of chemotherapy-induced peripheral neuropathy signs and symptoms has been hampered because of the lack of simple, reliable, and valid measures. The study objective was to examine the internal consistency and interrater reliability as well as the structural validity of a 5-component total neuropathy score-reduced (TNSr) variant and a chemotherapy-induced neuropathy-specific Neuropathic Pain Scale. One hundred seventeen outpatients receiving taxanes or platinums were assessed by a consistent nurse practitioner using the 2 instruments. Ten subjects participated in interrater reliability testing. Mean scores and SDs for individual items were low. The strength item was deleted because of low interitem correlations and a floor effect. The reflex item was deleted because of low interitem correlations and its negative influence on Cronbach alpha. Pin sensibility was deleted because of low factor loadings. The TNSr-short form and the chemotherapy-induced neuropathy-specific Neuropathic Pain Scale formed 2 distinct factors, providing evidence of structural validity. Cronbach alpha's for the 2 instruments were .80 and .96, respectively. The TNSr interrater reliability results suggested acceptable rater concordance, but minor revisions could further improve scoring precision. Clinimetric evidence supports the use of 2 new instruments when monitoring taxane- and platinum-related neuropathy and pain. Further instrument modifications are recommended, followed by additional testing in diverse populations. With these new instruments, nurses can more easily incorporate prospective neuropathy assessment into daily clinical practice. The outcome will be improved symptom awareness by oncology clinicians and patients, leading to fewer chemotherapy-induced peripheral neuropathy-related devastating effects on functionality and quality of life.

Prospective assessment of chemotherapy-induced peripheral neuropathy due to weekly paclitaxel in patients with advanced or metastatic breast cancer (CSP-HOR 02 study)

The aim of this study was to prospectively evaluate chemotherapy-induced peripheral neuropathy (CIPN) using a patient-based instrument, the Patient Neurotoxicity Questionnaire (PNQ) and a physician-based instrument, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) in patients with advanced or metastatic breast cancer who were treated with weekly paclitaxel. CIPN symptoms were prospectively assessed in 35 patients using the PNQ, NCI-CTC, and the Functional Assessment of Cancer Therapy (FACT)-Taxane including neurotoxicity component (Ntx) at the baseline, and 8 and 16 weeks after starting chemotherapy. For sensory neuropathy symptoms, the reported incidence of CIPN was significantly increased during active treatment in terms of both the PNQ and NCI-CTC assessments. In contrast, there was a notable increase of patient motor neuropathy symptoms that were elucidated only by the PNQ. The PNQ grades of CIPN were widely distributed in the patient population as compared with the NCI-CTC grades for both sensory and motor neuropathy. The sensory PNQ grade was correlated with sensory NCI-CTC grade (r = 0.58) and Ntx (r = 0.51), and the motor PNQ grade was correlated with Ntx (r = 0.57). The PNQ appears to be more sensitive and responsive than the NCI-CTC for CIPN; the PNQ appears to have diagnostic validity for evaluating CIPN in patients who are receiving neurotoxic chemotherapy.

A Questionnaire Survey of Physicians' Perspectives Regarding the Assessment of Chemotherapy-induced Peripheral Neuropathy in Patients with Breast Cancer

Since there is now growing interest in the incorporation of patient-reported outcome measures in cancer clinical trials, a patient-based questionnaire, the Patient Neurotoxicity Questionnaire (PNQ) was developed to quantify the symptoms and severity of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to evaluate the physicians' perspectives regarding the utility and diagnostic value of PNQ. A questionnaire was sent to 61 physicians who participated in a Phase III randomized trial of adjuvant chemotherapy in breast cancer (AC followed by taxane versus taxane alone) that used the PNQ to assess CIPN. Forty-seven out of 61 physicians (77%) responded. The majority considered neurosensory symptoms the diagnostic hallmark for CIPN and most regarded interference with activities of daily living (ADLs) as definite justification for treatment modifications. For neurosensory disturbance, the majority of physicians indicated that Grade D severity (moderate to severe symptoms interfering with ADLs) should result in treatment postponement and Grade E severity (severe symptoms preventing most ADLs) should result in treatment discontinuation. Similarly, for neuromotor disturbance, over half of the physicians replied that Grade C (moderate symptoms not interfering with ADLs), D and E severity should result in dose reduction, treatment postponement and treatment discontinuation, respectively. Eighty-four percentage of the physicians reported that the use of the PNQ was helpful in the diagnosis and assessment of patients at risk of CIPN. The PNQ appears to be a useful instrument for the diagnosis and grading of CIPN, as well as for clinical decision-making regarding treatment modifications secondary to CIPN.

Oral Glutamine for the Prevention of Chemotherapy-Induced Peripheral Neuropathy

To evaluate the role of glutamine in the reduction of peripheral neuropathy associated with neurotoxic chemotherapy. Relevant literature was accessed through PubMed (1990-May 2008), using the search terms glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkaloids. References in the identified articles were also reviewed for pertinent information. Studies evaluating the role of oral glutamine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) were included. Studies regarding the role of glutamine in the reduction of other radiation- and chemotherapy-related toxicities, such as mucositis, cardiotoxicity, diarrhea, and cachexia, were excluded. CIPN is a significant adverse effect associated with neurotoxic chemotherapy, particularly with taxanes, platinum compounds, and vinca alkaloids. There is no standard therapy for the treatment of this dose-limiting reaction. Glutamine is a nonessential amino acid that is thought to have a neuroprotective role, possibly due to the upregulation of nerve growth factor. Two studies revealed that oral glutamine was effective in reducing peripheral neuropathy associated with high-dose paclitaxel, as evidenced by a reduction in numbness, dysesthesias, and motor weakness, as well as a smaller loss of vibratory sensation. Another study found that glutamine effectively reduced peripheral neuropathy in patients with colorectal cancer being treated with oxaliplatin, thereby decreasing the need for an oxaliplatin dose reduction. However, data are limited by small sample sizes in these studies and the lack of placebo-controlled, randomized clinical trials. Larger, well-designed, placebo-controlled trials assessing both safety and efficacy of oral glutamine are warranted before this agent can be definitively recommended for the prevention of CIPN in patients treated with high-dose paclitaxel or oxaliplatin.