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IntroductionChemotherapy-induced peripheral neuropathy (CIPN) continues to be a major concern for oncological practise considering the increasing number of cancer survivors and the lack of standardised prevention or treatment [1]. The incidence of CIPN depends on the chemotherapy agent administered but is estimated to occur in one third of all pati...
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... blood pathology tests for this patient before chemothera- py was in the reference range, 107 pmol/L (ref range >35 pmol/L) presented in Table 2. After chemotherapy admin- istration (Table 3 documents the chemotherapy regime), the vitamin B12 status decreased and was deemed as deficient as presented in Table 2 and Fig. 1. After supplementation with a B group vitamin complex (equivalent to 1000 μg/day of vita- min B12) and receiving one intramuscular vitamin B12 injec- tion (dose 1000 μg), the blood vitamin B12 level reverted back to baseline (106 pmol/L). ...
Citations
... It occurs in approximately 30-80% of patients treated with antineoplastic drugs such as platinum compounds, taxanes, and vinca alkaloids [33,34]. Several studies have reported functional vitamin B12 deficiency, which manifests as a temporary decrease in vitamin B12 due to oxidative stress caused by chemotherapy, even if vitamin B12 levels are normal [35][36][37][38]. Because it is difficult to differentiate between vitamin B12 deficiency and chemotherapy-induced peripheral neuropathy in patients treated with chemotherapy, patients who received adjuvant or palliative chemotherapy were excluded from this analysis. ...
Simple Summary
The management of vitamin B12 deficiency in patients who underwent total gastrectomy remains unclear. This study evaluated the effect of vitamin B12 replacement intervals on the clinical symptoms and laboratory findings in gastric cancer patients with vitamin B12 deficiency after total gastrectomy. The vitamin B12 levels after replacement were significantly higher in the regular replacement group than in the lab-based replacement group. The post-replacement serum hemoglobin levels and symptoms were comparable between the two groups.
Abstract
The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients.
... A retrospective study showed vitamin B12 therapy improved neurologic symptoms in palliative care patients with CIPN and neuropathic pain [36]. Another RCT showed vitamin B12 reduced the onset and severity of CIPN, but had no statistical significance on the total neurological symptoms in patients on paclitaxel, vincristine, and taxo/carboplatin [37]. The same study also showed patients had reduced sensory CIPN on a B vitamin complex. ...
This review aims to discuss pathophysiology, diagnosis, clinical presentation, and treatment of chemotherapy-induced peripheral neuropathy. Agent-specific presentation and pathophysiology is also being discussed.
As new systemic oncological treatments continue to be developed, the number of cancer survivors continues to grow. Survivors are living longer with the long-term side effects of oncological treatments. We reviewed the pathophysiology of agent-specific chemotherapy-induced peripheral neuropathy and the updates in its treatment and preventative tools.
Chemotherapy-induced peripheral neuropathy is a debilitating long-term side effect that often impairs cancer survivors’ function and quality of life. The increasing life expectancy of cancer survivors has resulted in increased prevalence of this condition. Understanding its intricacies can provide physicians with better treatment tools and research opportunities to develop or identify new therapeutic agents.
... All these agents are supplement preparations but no natural or herbal products was found to be studied against TIPN alone. Among 13 relevant papers, we found 10 clinical trials (17)(18)(19)(20)(21)(22)(23)(24)(25)(26), one case study (27) and two animal studies on rat (28,29). Herein, details of each study were described according to the supplement that is used. ...
... Patient received vitamin B12 (1000 μg intramuscularly and 1000 μg orally daily) and B complex vitamins continued for two months. The patient TIPN reversed to grade 1 on NCI-CTC scales (27). ...
... Some patients with developed neuropathy in placebo group shows lower blood level of vitamin B12 than baseline (25). Blood level of vitamin B12 was lower than baseline after chemotherapy but other B vitamins blood level did not reduce (27). A case study also demonstrated that vitamin B12 can be effective against TIPN. ...
Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect of chemotherapy without any specific treatment. The aim of this paper is to evaluate the effects of natural products and supplements on TIPN. PubMed, Google Scholar and Web of Science databases were searched through August 2022 regarding TIPN and effects of natural products and supplement therapy. Data consists of preclinical studies, randomized controlled trials and case reports. After screening of 230 papers, we found 13 relevant animal and human studies regarding possible benefits of vitamin E, glutamine, omega-3, acetyl-L-carnitine and group of B vitamins on TIPN. Results demonstrated that vitamin E can be helpful on prevention and duration of TIPN. Glutamine and B vitamins showed hopeful results on reducing pain sensation. Omega-3 also shows promising results on incidence of TIPN. However, acetyl-L-carnitine might develop and worsen neuropathy. Although some supplements revealed promising effects on prevention and treatment of TIPN, researches are still limited and we need further long-term large sample size trials to confirm clinical efficacy of these supplements. J Pharm Care 2023; 40(53): 40-53.
... It is also of note that both metabolites (MMA and Hcy) were elevated along together in only 23% of patients among them both metabolites were measured, while isolated elevations of MMA (in 55% of patients) were signi cantly more frequent than isolated elevations in Hcy (in 22% of patients), p < 0.001[53]. Solomon et al. also reported that elevation of MMA and/or Hcy values, consistent with functional vitamin B12 de ciency, occurred in more than half of patients studied even when B12 values were markedly elevated (≥1500 pg/ml)[53].Our ndings of a signi cant difference in serum HoloTC, vitamin B6 and folate concentrations between at the baseline and after the completion of chemotherapy regimen is in agreement with a clinical study of a single breast cancer patient[54], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range >35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range[54]. ...
... Solomon et al. also reported that elevation of MMA and/or Hcy values, consistent with functional vitamin B12 de ciency, occurred in more than half of patients studied even when B12 values were markedly elevated (≥1500 pg/ml)[53].Our ndings of a signi cant difference in serum HoloTC, vitamin B6 and folate concentrations between at the baseline and after the completion of chemotherapy regimen is in agreement with a clinical study of a single breast cancer patient[54], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range >35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range[54]. ...
Purpose
Cancer treatment itself and particularly chemotherapy unavoidably affects host cells, often producing a variety of side effects e.g., nausea, vomiting, oral pain, diarrhea, fever and chills, and further decrease in appetite, physical activity, and body weight. These effects, together with biochemical and histological injuries to major organ systems, may leave the patient with a profound nutritional insufficiency. Early nutritional assessment can identify problems to help patients increase or maintain weight, improve their response to treatment, and reduce complications. This study aimed to determine the nutritional status of patients receiving chemotherapy.
Methods
A prospective study was conducted among 64 adults newly diagnosed cancer patients of various cancer sites, admitted to the Oncology Department at European Gaza Hospital (EGH) and scheduled for first cycle of chemotherapy. Nutritional status of each patient was assessed using Subjective global assessment (SGA) and anthropometry before the initiation of chemotherapy and after the completion of chemotherapy regimen. Forty-five patients out of a total of 64 patients were evaluated at baseline and after the completion of chemotherapy regimen for vitamin B12, holotranscobalamin (HoloTC), vitamin B6, Folate, methylmalonic acid (MMA), homocysteine (Hcy), albumin, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Dietary intake was assessed using 24-hour dietary recall (24HR).
Results: In this study, mean age of patients was 48.58 years. Males comprised 27(42.2%) of patients whereas female accounted for 37(57.8%). It has been found that 80.3% of subjects suffered from malnutrition (moderate and sever) after the completion of chemotherapy regimen based on SGA in comparison to 35.9% where malnourished before commencing the chemotherapy cycle. The results reported drastic reduction in all the vitamins and albumin after the completion of chemotherapy regimen. Vitamin B12 (355.0(IQR 115.0) to 219.0(IQR 177.0) pg/mL, P< 0.001), HoloTC (2.90(2.85) to1.30(IQR3.15) ng/mL, P < 0.001), vitamin B6 (83.40(IQR 27.65) to 70.70(IQR 38.45) ng/mL, P < 0.001), folate (6.60(IQR 3.00) to 5.30(IQR 2.75) ng/mL, P < 0.001); albumin (4.10(IQR 0.70) to 3.20(IQR 0.85) g/dL, P < 0.001).
Vitamin B12- related metabolites MMA and Hcy increased substantially indicating a functional B12 deficiency within the cells. MMA increased significantly from (3.90(IQR 3.00) to 49.70(IQR 32.00) ng/ml, P< 0.001) and Hcy also reported significant increase (3.90(IQR 0.85) to 12.60(IQR 7.05) ng/ml, P < 0.001) which is consider as independent risk factor for cardiovascular diseases. Dietary intake in terms of macronutrients and micronutrients changed significantly after the completion of chemotherapy regimen.
Conclusion: Cancer patients who received chemotherapy were at risk of malnutrition hence it is a wise practice to conduct thoroughly and deep nutritional assessment for each patient at the baseline, during treatment and after the completion of chemotherapy regimen. This research has clearly indicated the possibilities of functional vitamin B12 deficiency and other deficiencies among cancer patients who were treated with chemotherapy.
... Our ndings of a signi cant difference in serum HoloTC, vitamin B6 and folate concentrations between at the baseline and after the completion of chemotherapy regimen is in agreement with a clinical study of a single breast cancer patient [54], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [54]. ...
... Our ndings of a signi cant difference in serum HoloTC, vitamin B6 and folate concentrations between at the baseline and after the completion of chemotherapy regimen is in agreement with a clinical study of a single breast cancer patient [54], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [54]. ...
Background and aim: Cancer treatment itself and particularly chemotherapy unavoidably affects host cells, often producing a variety of side effects e.g., nausea, vomiting, oral pain, diarrhea, fever and chills, and further decrease in appetite, physical activity, and body weight. These effects, together with biochemical and histological injuries to major organ systems, may leave the patient with a profound nutritional insufficiency.
Early nutritional assessment can identify problems to help patients increase or maintain weight, improve their response to treatment, and reduce complications. This study aimed to determine the nutritional status of patients receiving chemotherapy.
Methods: A prospective study was conducted among 64 adults newly diagnosed cancer patients of various sites, admitted to the oncology department at European Gaza Hospital (EGH) and scheduled for first cycle of chemotherapy. Nutritional status of each patient was assessed using Subjective global assessment (SGA) and anthropometry before the initiation of chemotherapy and after the completion of chemotherapy regimen. Forty-five patients out of a total of 64 patients were evaluated at baseline and after the completion of chemotherapy regimen for vitamin B12, holotranscobalamin (HoloTC), vitamin B6, Folate, methylmalonic acid (MMA), homocysteine (Hcy), albumin, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Dietary intake was assessed using 24-hour dietary recall (24HR).
Results: In this study, mean age of patients was 48.58 years. Males comprised 27(42.2%) of patients whereas female accounted for 37(57.8%). It has been found that 80.3% of subjects suffered from malnutrition (moderate and sever) after the completion of chemotherapy regimen based on SGA in comparison to 35.9% where malnourished before commencing the chemotherapy cycle. The results reported drastic reduction in all the vitamins and albumin after the completion of chemotherapy regimen. Vitamin B12 (355.0(115.0) to 219.0(177.0) pg/ml, p< 0.001), holoTC (2.90(2.85) to1.30(3.15) ng/ml, p < 0.001), vitamin B6 (83.40(27.65) to 70.70(38.45) ng/ml, p < 0.001), folate (6.60(3.00) to 5.30(2.75) ng/ml, p < 0.001); albumin (4.10(0.70) to 3.20(0.85) mg/dl, p < 0.001).
Vitamin B12- related metabolites MMA and Hcy increased substantially indicating a functional B12 deficiency within the cells. MMA increased significantly from (3.90(3.00) to 49.70(32.00) ng/ml, p < 0.001) and Hcy also reported significant increase (3.90(0.85) to 12.60(7.05) ng/ml, p < 0.001) which is consider as independent risk factor for cardiovascular diseases. Dietary intake in terms of macronutrients and micronutrients changed significantly after the completion of chemotherapy regimen.
Conclusion: Cancer patients who received chemotherapy were at risk of malnutrition hence it is a wise practice to conduct thoroughly and deep nutritional assessment for each patient at the baseline, during treatment and after the completion of chemotherapy regimen. This research has clearly indicated the possibilities of functional vitamin B12 deficiency and other deficiencies among cancer patients who were treated with chemotherapy.
... The incidence of CIPN depends on the chemotherapy agent administered but it is estimated to occur in one third of all patients undergoing chemotherapy [8,9]. The prevalence of CIPN has been estimated to be 68.1% at the rst month after chemotherapy, 60.0% at 3 months [10]. ...
... By far diabetic neuropathy is the most prevalent chronic complication of diabetes with prevalence rates ranging from 10-26% in newly diagnosed adults with diabetes [42]. concentrations reduced signi cantly after the completion of chemotherapy regimen) is in agreement with a clinical study of a single breast cancer patient [9], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [9]. ...
... concentrations reduced signi cantly after the completion of chemotherapy regimen) is in agreement with a clinical study of a single breast cancer patient [9], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [9]. In our regression model, another noteworthy nding, a signi cant association between CIPN indicator (PNQ) score and serum folate levels as well as serum vitamin B6 levels. ...
Background and aim
Chemotherapy- induced peripheral neuropathy (CIPN) is a common, significant, debilitating symptom of anticancer treatment, continues to plague patients and the medical fraternity. CIPN interferes with optimal treatment of active disease resulting in the need for dose reduction, treatment delay and even premature cessation of chemotherapy and can severely affects the quality of life (QoL). Functional vitamin B12 deficiency, defined by elevated levels of vitamin B12- dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal serum B12 values, may cause neuropathy and neuropathic pain. This study aimed to determine the role of functional vitamin B12 deficiency in the development of CIPN among cancer patients undergoing chemotherapy.
Methods
A prospective study design (short cohort study) was conducted to achieve the study objectives, utilizing non-probability purposive sampling technique. A consecutive case series of 64 adult (≥ 18 years) newly diagnosed cancer patients of various sites, registered and scheduled to receive the first cycle of chemotherapy were recruited from the Oncology Department of European Gaza Hospital (EGH). At two different points of time, at the baseline before the initiation of the first cycle of chemotherapy (pre) and after the completion of chemotherapy regimen (post), vitamin B12 status was evaluated using serum vitamin B12 and it is related metabolites methylmalonic acid (MMA) and homocysteine (Hcy), and CIPN was evaluated using patient neurotoxicity questionnaire (PNQ). The direction of association between CIPN and the indicator factors of functional vitamin B12 deficiency as well as other predicted variables was evaluated using stepwise multiple linear regression (MLR) analysis.
Results
Mean age of patients was 48.58 years. Males comprised 27(42.2%) of patients whereas female accounted for 37(57.8%). The results reported the presence of a functional vitamin B12 deficiency, such that there is a drastic reduction in serum vitamin B12 level (355.0(115.0) to 219.0(177.0) pg/ml, p < 0.001), accompanied by a significant increase in it is related metabolites MMA (3.9(3.0) to 49.7(32.0) ng/ml, p < 0.001) and Hcy (3.90(0.85) to 12.60(7.05) ng/ml, p < 0.001) after the completion of chemotherapy regimen.
The MLR model ensures a significant relationship between an MMA “the best sensitive indicator of functional vitamin B12 deficiency” and CIPN indicator, PNQ score significantly increased with increasing serum MMA level (b = 0.02, R² = 0.30, p = 0.001). An increase of MMA by one significantly increases the CIPN indicator score by 0.02 as b = 0.02. Furthermore, a one-point increase in the Subjective Global Assessment (SGA) increased the PNQ score by 0.31 (b = 0.31, R² = 0.54, p = 0.004). Compared with non-diabetic patients, being a diabetic will increase the score of CIPN indicator by 0.38 (b = 0.38, R2 = 0.61, p = 0.032). A platinum compounds increase the CIPN indicator by 0.51 (b= 0.51, R² = 0.79, p = 0.001). An increase in the patient age increased his/her PNQ score by 0.02 (b = 0.02, R2 = 0.83, p = 0.001). Moreover, the final model asserts that there is a significant association between the criterion variable (CIPN) and the two predictor variables (folate) and (vitamin B6), which were p = 0.012 and p = 0.039, respectively. A higher difference in folate (b = 0.15, 95% CI, 0.02,0.27) and vitamin B6 (b = 0.01, 95% CI, 0.0, 0.02) will be associated with an increase in the CIPN indicator score. Finally, the MLR results indicated that a consumption of three meals daily will lead to a decrease in CIPN indicator score by 1.07 (b = -1.07, R²= 0.74, p < 0.001).
Conclusion
Functional vitamin B12 deficiency is a distinct risk factor in the development of CIPN in cancer patients undergoing chemotherapy. This is clinically important, as early detection and treatment of functional vitamin B12 deficiency may prevent and/or alleviate CIPN symptoms. Further studies are required to evaluate the impact of vitamin B12 therapy in the management and/or prevention of CIPN.
... The incidence of CIPN depends on the chemotherapy agent administered but it is estimated to occur in one third of all patients undergoing chemotherapy [8,9]. The prevalence of CIPN has been estimated to be 68.1% at the rst month after chemotherapy, 60.0% at 3 months [10]. ...
... By far diabetic neuropathy is the most prevalent chronic complication of diabetes with prevalence rates ranging from 10-26% in newly diagnosed adults with diabetes [42]. concentrations reduced signi cantly after the completion of chemotherapy regimen) is in agreement with a clinical study of a single breast cancer patient [9], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [9]. ...
... concentrations reduced signi cantly after the completion of chemotherapy regimen) is in agreement with a clinical study of a single breast cancer patient [9], which found a pronounced HoloTC de ciency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague's, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [9]. In our regression model, another noteworthy nding, a signi cant association between CIPN indicator (PNQ) score and serum folate levels as well as serum vitamin B6 levels. ...
Background and aim: Chemotherapy- induced peripheral neuropathy (CIPN) is a common, significant, debilitating symptom of anticancer treatment, continues to plague patients and the medical fraternity. CIPN interferes with optimal treatment of active disease resulting in the need for dose reduction, treatment delay and even premature cessation of chemotherapy and can severely affects the quality of life (QoL). Functional vitamin B12 deficiency, defined by elevated levels of vitamin B12- dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal serum B12 values, may cause neuropathy and neuropathic pain. This study aimed to determine the role of functional vitamin B12 deficiency in the development of CIPN among cancer patients undergoing chemotherapy. Methods A prospective study design (short cohort study) was conducted to achieve the study objectives, utilizing non-probability purposive sampling technique. A consecutive case series of 64 adult (≥ 18 years) newly diagnosed cancer patients of various sites, registered and scheduled to receive the first cycle of chemotherapy were recruited from the Oncology Department of European Gaza Hospital (EGH). At two different points of time, at the baseline before the initiation of the first cycle of chemotherapy (pre) and after the completion of chemotherapy regimen (post), vitamin B12 status was evaluated using serum vitamin B12 and it is related metabolites methylmalonic acid (MMA) and homocysteine (Hcy), and CIPN was evaluated using patient neurotoxicity questionnaire (PNQ). The direction of association between CIPN and the indicator factors of functional vitamin B12 deficiency as well as other predicted variables was evaluated using stepwise multiple linear regression (MLR) analysis. Results Mean age of patients was 48.58 years. Males comprised 27(42.2%) of patients whereas female accounted for 37(57.8%). The results reported the presence of a functional vitamin B12 deficiency, such that there is a drastic reduction in serum vitamin B12 level (355.0(115.0) to 219.0(177.0) pg/ml, p < 0.001), accompanied by a significant increase in it is related metabolites MMA (3.9(3.0) to 49.7(32.0) ng/ml, p < 0.001) and Hcy (3.90(0.85) to 12.60(7.05) ng/ml, p < 0.001) after the completion of chemotherapy regimen. The MLR model ensures a significant relationship between an MMA “the best sensitive indicator of functional vitamin B12 deficiency” and CIPN indicator, PNQ score significantly increased with increasing serum MMA level (b = 0.02, R2 = 0.30, p = 0.001). An increase of MMA by one significantly increases the CIPN indicator score by 0.02 as b = 0.02. Furthermore, a one-point increase in the Subjective Global Assessment (SGA) increased the PNQ score by 0.31 (b = 0.31, R2 = 0.54, p = 0.004). Compared with non-diabetic patients, being a diabetic will increase the score of CIPN indicator by 0.38 (b = 0.38, R2 = 0.61, p = 0.032). A platinum compounds increase the CIPN indicator by 0.51 (b= 0.51, R2 = 0.79, p = 0.001). An increase in the patient age increased his/her PNQ score by 0.02 (b = 0.02, R2 = 0.83, p = 0.001). Moreover, the final model asserts that there is a significant association between the criterion variable (CIPN) and the two predictor variables (folate) and (vitamin B6), which were p = 0.012 and p = 0.039, respectively. A higher difference in folate (b = 0.15, 95% CI, 0.02,0.27) and vitamin B6 (b = 0.01, 95% CI, 0.0, 0.02) will be associated with an increase in the CIPN indicator score. Finally, the MLR results indicated that a consumption of three meals daily will lead to a decrease in CIPN indicator score by 1.07 (b = -1.07, R2= 0.74, p < 0.001). Conclusion Functional vitamin B12 deficiency is a distinct risk factor in the development of CIPN in cancer patients undergoing chemotherapy. This is clinically important, as early detection and treatment of functional vitamin B12 deficiency may prevent and/or alleviate CIPN symptoms. Further studies are required to evaluate the impact of vitamin B12 therapy in the management and/or prevention of CIPN.
... The moderate usefulness of duloxetine for treatment of CIPN in cancer patients treated with various cytotoxic chemotherapeutics including paclitaxel has also been supported by clinical trials in Japan [19,20]. Nonetheless, apart from opioids and non-steroidal anti-inflammatory drugs (NSAIDs) that are often used to treat cancer pain, vitamin B12, pregabalin and Goshajinkigan, a Chinese polyherbal medicine, in addition to duloxetine, are commonly prescribed for treatment of CIPN in Japan [21], although there is poor evidence for their effectiveness against CIPN [17,[22][23][24]. ...
... As described in the previous report from survey of the management of CIPN in Japan [21], the present study ascertained that many of female cancer patients with PIPN were prescribed with pregabalin, mecobalamin or Goshajinkigan (see Table 3) in spite of poor evidence for their effectiveness against CIPN [17,[22][23][24], while relatively few patients with PIPN received duloxetine, the only medicine that has moderate evidence for the use to treat the established CIPN [17] (see Table 3 and Fig 2). Goshajinkigan, a polyherbal medicine that legally requires a prescription to be dispensed in Japan, contains fixed proportions of 10 crude herbal extracts, i.e. achyranthes root, rehmannia root, dioscorea, rhizome, cornus fruit, alisma rhizome, plantago seed moutan bark, pariah sclerotium, aconite root and cinnamon bark [35]. ...
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse reaction in cancer patients treated with several cytotoxic anticancer agents including paclitaxel. Duloxetine, an antidepressant known as a serotonin-noradrenalin reuptake inhibitor, is the only agent that has moderate evidence for the use to treat painful CIPN. The present retrospective cohort study aimed to analyze risk factors for paclitaxel-induced peripheral neuropathy (PIPN), and investigate ongoing prescription drug use for PIPN in Japan. Female breast and gynecologic cancer patients who underwent paclitaxel-based chemotherapy at a single center in Japan between January 2016 and December 2019 were enrolled in this study. Patients’ information obtained from electronic medical records were statistically analyzed to test possible risk factors on PIPN diagnosis. Patients’ age, total paclitaxel dose, the history of female hormone-related diseases, hypertension and body mass index (BMI), but not additional platinum agents, were significantly associated with increased PIPN diagnosis. Drugs prescribed for PIPN included duloxetine, pregabalin, mecobalamin and Goshajinkigan, a polyherbal medicine, regardless of poor evidence for their effectiveness against CIPN, and were greatly different between breast and gynecologic cancer patients diagnosed with PIPN at the departments of Surgery and Gynecology, respectively. Thus, older age, greater total paclitaxel dose, the history of estrogen-related diseases, hypertension and BMI are considered risk factors for PIPN in paclitaxel-based chemotherapy of female cancer patients. It appears an urgent need to establish a guideline of evidence-based pharmacotherapy for PIPN.
... Despite the known link across etiologies, the role of these deficiencies as risk factors for chemotherapy-induced PN has not been well defined [20]. Deficiency of B vitamins and vitamin D have been associated with increased chemotherapy-induced PN and past case reports indicate supplementation may be an effective treatment option in deficient patients [21][22][23][24]. Nutritional deficiencies present an attractive option as a predictive biomarker because they are easily detected by commonly conducted clinical labs and are often modifiable through nutritional supplementation or dietary modification. ...
PurposeApproximately 25% of patients receiving weekly paclitaxel for breast cancer require treatment disruptions to avoid severe, irreversible peripheral neuropathy (PN). Vitamin insufficiencies are PN risk factors in many diseases, but their relevance to chemotherapy-induced PN is unknown.Methods
We investigated whether baseline insufficiency of vitamin D, vitamin B12, folate, or homocysteine increased PN in patients with breast cancer receiving weekly paclitaxel in a retrospective analysis of a prospective observational study. Patient-reported PN was collected at baseline and during treatment on the Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (CIPN20). The primary analysis tested associations between vitamin deficiency and the maximum increase from baseline in the CIPN20 sensory subscale (ΔCIPN8). Secondary analyses tested for association with PN-induced treatment disruptions and adjusted associations for treatment and clinical variables.Results25-hydroxy-vitamin D was the only nutrient with sufficient deficiency (< 20 ng/mL) for analysis (15/37 = 41%). Vitamin D-deficient patients had a greater mean PN increase than non-deficient patients (ΔCIPN8 ± SD, 36 ± 23 vs. 16 ± 16, p = 0.003) and a non-significant, approximately threefold increase in risk of treatment disruption (OR 2.98, 95% CI [0.72, 12.34], p = 0.16). In multivariable models adjusted for clinical and treatment variables, baseline vitamin D level was inversely associated with PN (β = − 0.04, p = 0.02).Conclusion
Pre-treatment vitamin D deficiency was associated with PN in women receiving weekly paclitaxel for breast cancer. Vitamin D deficiency may be an easily detected PN risk factor that could be resolved prior to treatment to prevent PN, avoid treatment disruptions, and improve treatment outcomes.
... Vitamin B12 deficiency, which elevates the risk of chemotherapy-induced peripheral neuropathy, is increased especially when using the taxol-containing chemotherapeutic agents, leading to neurotoxic effects (41). ...
Nutritional disorders include malnutrition and inadequate nutrition, overweight and obesity, micronutrient disorders and refeeding syndrome. According to the European Society for Clinical Nutrition and Metabolism, sarcopenia and fragility are nutrition-related conditions with complex and multiple pathogenic infrastructure. Inadequate nutrition is also considered as protein-energy malnutrition and is often accompanied by micronutrient as well as macronutrient deficiencies. Macronutrients such as carbohydrates, proteins, and fats are essential nutrients that provide energy to the body and aid in growth. Micronutrients such as vitamins, minerals, and trace elements are necessary for many special functions in the body. Meanwhile, drug intake can lead to increased morbidity and mortality and decreased quality of life by causing malnutrition through various mechanisms. The pharmacological and pharmaceutical properties of drugs can affect the intake, digestion, absorption, storage, metabolism, and elimination of nutrients, causing imbalance in the amount of nutrients required in the body. Polypharmacy makes this situation even more risky. Many of the patients’ symptoms or complaints received by physicians in their daily practice are associated with drug-induced nutritional disorders. When evaluating symptoms, physicians should also assess whether the symptoms are related to the disease, drug side effects, or drug-induced nutritional disorders. Instead of thinking that the resulting symptoms are simply “part of the disease” or “old age” and starting to take additional medication to resolve them, physicians should focus thoroughly on the event and examine what problems that the drugs used may cause in patients and the underlying reasons for deciding what they can do to eliminate them. This intervention should be investigated. Hence, this review aimed to explore the importance of the subject by mentioning the mechanisms of the negative effects of drugs on nutrition and providing examples of commonly used drugs.
