Acupuncture for Chemotherapy-Induced Peripheral Neuropathy (Cipn): A Pilot Study Using Neurography The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients. Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Exercise training can modify the natural history of diabetic peripheral neuropathy. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial. Clinical Study on the Prevention of Oxaliplatin-Induced Neurotoxicity with Guilongtongluofang: Results of a Randomized, Double-Blind, Placebo-Controlled Trial A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of goshajinkigan to prevent oxaliplatin-induced neuropathy Effect of acupuncture administered in a group setting on pain and subjective peripheral neuropathy in persons with human immunodeficiency virus disease. Chemotherapy-induced peripheral neuropathy, physical activity and health-related quality of life among colorectal cancer survivors from the PROFILES registry The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study A Trial of Scrambler Therapy in the Treatment of Cancer Pain Syndromes and Chronic Chemotherapy-Induced Peripheral Neuropathy Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. Clinical study of Jiawei Huangqi Guizhi Wuwu Decoction in preventing and treating peripheral neuro-sensory toxicity caused by oxaliplatin. Glutamine supplementation in cancer patients. Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. A Highly Successful and Novel Model for Treatment of Chronic Painful Diabetic Peripheral Neuropathy Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Clinical effects of acupuncture for diabetic peripheral neuropathy. Evidence-based Complementary and Alternative Medicine. Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity
Objectives Chemotherapy-induced peripheral neuropathy ( CIPN ) can produce severe neurological deficits and neuropathic pain and is a potential reason for terminating or suspending chemotherapy treatments . Specific and effective curative treatments are lacking . Methods A pilot study was conducted to evaluate the therapeutic effect of acupuncture  on CIPN as measured by changes in nerve conduction studies ( NCS ) in six patients treated with acupuncture for 10 weeks in addition to best medical care and five control patients who received the best medical care but no specific treatment for CIPN .  Results In five of the six patients treated with acupuncture , NCS improved after treatment . In the control group , three of five patients did not show any difference in NCS , one patient improved and one showed impaired NCS . Conclusion The data suggest that acupuncture has a positive effect on CIPN . The encouraging results of this pilot study justify a r and omised controlled trial of acupuncture in CIPN on the basis of NCS BACKGROUND Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment . Calcium and magnesium ( Ca/Mg ) infusions are frequently used to prevent this toxicity . However , concerns about a negative impact of Ca/Mg infusions on outcome have been raised . We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer ( ACC ) patients treated in the phase III CAIRO2 study . MATERIAL S AND METHODS Seven hundred and fifty five previously untreated ACC patients were r and omised between treatment with  capecitabine , oxaliplatin and bevacizumab or the same combination with the addition of cetuximab . Patients were retrospectively divided into two groups : patients in the Ca/Mg(+ ) group received Ca/Mg at least during their first treatment cycle , and patients in the Ca/Mg(- ) group did not . RESULTS Seven hundred and thirty two patients were evaluable for this analysis . The Ca/Mg(+ ) group consisted of 551 patients , the Ca/Mg(- ) group consisted of 181 patients . The incidence of all grade neurotoxicity in the Ca/Mg(+ ) group and the Ca/Mg(- ) group was 85 % and 92 % , respectively ( p = 0.02 ) , and the incidence of grade ≥ 2 neurotoxicity was 40 % and 45 % , respectively ( p = 0.22 ) . The median PFS in the Ca/Mg(+ ) versus Ca/Mg(- ) group was 10.1 versus 10.7 months ( p = 0.92 ) , the median OS was 19.8 versus 20.7 months ( p = 0.10 ) , and the response rate was 43.1 % versus 50 % ( p = 0.11 ) , respectively . CONCLUSIONS In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity . Ca/Mg infusions did not affect the clinical efficacy of treatment Oxaliplatin is effective in the treatment of metastatic colorectal cancer ( MCRC ) patients ; however , severe neurotoxicity develops frequently . To assess the efficacy of oral glutamine for preventing neuropathy induced by oxaliplatin , a pilot study was performed . A total of 86 patients with MCRC treated at Taipei Veterans General Hospital were enrolled .  Oxaliplatin ( 85 mg/m(2 ) , days 1 and 15 ) plus weekly bolus 5-fluorouracil ( 5-FU ; 500 mg/m(2 ) ) and folinic acid ( FA ; 20 mg/m(2 ) ) on days 1 , 8 , and 15 were given every 28 days as first-line treatment . Patients were r and omized to receive ( glutamine group ; n = 42 ) or not receive ( control group ; n = 44 ) glutamine ( 15 g twice a day for seven consecutive days every 2 weeks starting on the day of oxaliplatin infusion ) . Efficacy of chemotherapy , neurological toxicity , and electrophysiological alterations were assessed . A lower percentage of grade 1 - 2 peripheral neuropathy was observed in the glutamine group ( 16.7 % versus 38.6 % ) after two cycles of treatment , and a significantly lower incidence of grade 3 - 4 neuropathy was noted in the glutamine group after four cycles ( 4.8 % versus 18.2 % ) and six cycles ( 11.9 % versus 31.8 % ) . By adding glutamine , interference with activities of daily living was lower ( 16.7 % versus 40.9 % ) , and need for oxaliplatin dose reduction was lower ( 7.1 % versus 27.3 % ) . There were no significant between-group differences in response to chemotherapy ( 52.4 % versus 47.8 % ) , electrophysiological abnormalities , grade 3 - 4 non-neurological toxicities ( 26.2 % versus 22.8 % ) , or survival . These data indi-cate that oral glutamine significantly reduces the incidence and severity of peripheral neuropathy of MCRC patients receiving oxaliplatin without affecting response to chemotherapy and survival BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a  control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) .  Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001 , for both ) . The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P<.05 , and 29.8 % vs. 6.45 % , P<.05 , respectively ) . In addition , the percentage of diabetic patients who developed increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P<.05 ) . Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05 ) ; no significant change in Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN Acetyl-L-carnitine ( ALC ) improves  non-oncological neuropathies .  We tested oral ALC ( 1 g tid ) for 8 weeks in 25 patients with neuropathy grade 3 ( common toxicity criteria --CTC ) during paclitaxel or cisplatin therapy , or grade 2 persisting for at least three months after discontinuing the drugs . An independent neurologist assessed patients before and after ALC . All patients except one reported symptomatic relief , and only two described grade 1 nausea . The sensory neuropathy grade improved in 15 of 25 ( 60 % ) , and motor neuropathy in 11 of 14 patients ( 79 % ) . Total neuropathy score ( TNS ) that included neurophysiological measures improved in 23 ( 92 % ) . Amelioration of sensory amplitude and conduction velocity ( sural and peroneal nerves ) was measured in 22 and 21 patients , respectively . Symptomatic improvement persisted in 12 of 13 evaluable patients at median 13 months after ALC . In view of its effect in improving established paclitaxel- and cisplatin-neuropathy , we recommend ALC testing in preventing progression or revert symptoms during neurotoxic chemotherapy CONTEXT AND OBJECTIVE Oxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer . One of the main limitations to its use is induction of peripheral neuropathy . Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50 % . This study aim ed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy . DESIGN AND SETTING Prospect i ve , phase II , r and omized pilot study developed at a university hospital in the Greater ABC region . METHODS Patients were r and omized five days before starting oxaliplatin treatment , to receive either vitamin E or placebo until the end of the chemotherapy regimen . The outcome was evaluated using the Common Terminology Criteria for Adverse Events ( CTCAE ) , version 3 , and specific gradation scales for oxaliplatin-induced peripheral neuropathy .  Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included . Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions . RESULTS Eighteen patients were r and omized to the vitamin E group and 16 to the placebo group .  Cumulative incidence of 83 % with peripheral neuropathy grade s 1/2 was observed in the vitamin E group , versus 68 % in the placebo group ( P = 0.45 ) . A trend towards more diarrhea was observed among patients who received vitamin E ( 55.6 % vs. 18.8 % ; P = 0.06 ) . There were no other significant differences in toxicity between the groups . CONCLUSIONS No significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use Objective . Oxaliplatin-induced peripheral neurotoxicity continues to be a kind of frequent dose-limiting toxicity for many cancer patients . This study evaluated the preventive effects of Guilongtongluofang on peripheral neurotoxicity induced by oxaliplatin in patients with colorectal tumor . Patients and Methods . From May 2007 to May 2011 , we conducted a r and omized , double-blind , placebo-controlled trial . 120 patients of colorectal cancer treated with adjuvant oxaliplatin-based chemotherapy  were r and omly enrolled into the trial group and the control group . The trial group received Guilongtongluofang ( at a dose of 200 mL once a day ) from 3 days prior to chemotherapy . The control group received a placebo from 3 days prior to chemotherapy . Every 2-week cycle , neurotoxicity was evaluated using numeric rating scale for pain intensity and experienced relief . The primary endpoint was efficacy measurement which included oxaliplatin-induced neurotoxicity and tumor response . The differences of side effects between the two groups were also analyzed . Results . The percentage of grade s 1 - 2 neurotoxicity was significantly lower in the trial group than that in the control group ( 13.3 % versus 20.0 % ; P < 0.05 ) after two cycles of treatment . The difference of the percentage of neurotoxicity between the two groups was significant after six cycles ( 51.7 % versus 70.0 % ; P < 0.05 ) . Significant difference for the mean time to the development of grade 1 + neurotoxicity was found between the two groups ( 9.4 w in the trial group versus 6.5 w in the control group , P < 0.05 ) . The cumulative incidence of grade 1 or more sensory neurotoxicity was significantly lower in the trial group than that in the control group ( P < 0.05 ) . No significant differences of tumor response rate were found between the two groups the trial group and the control group . No significant difference was found between the trial group and the control group ( all P > 0.05 ) . Conclusion . This study provides evidence that Guilongtongluofang is a promising drug for the prevention of oxaliplatin-induced neurotoxicity in patients with colorectal cancer , and it does not reduce the efficacy of oxaliplatin Aim A r and omized , open label with blind assessment , controlled trial was performed to assess efficacy and adverse-event profile of vitamin E , given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy ( CIPN ) . Patients and methods A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were r and omly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study . Patients assigned to group I ( n=14 ) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II ( n=16 ) , who received no vitamin E supplementation and served as controls . The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy ( PNP ) score . Results The incidence of neurotoxicity differed significantly between groups , occurring in 3/14 ( 21.4 % ) of patients assigned to the vitamin E supplementation group and in 11/16 ( 68.5 % ) of controls ( p=0.026 ) . The relative risk ( RR ) of developing neurotoxicity was significantly higher in case of controls , RR=2.51 , 95 % C.I.=1.16–5.47 . Mean PNP scores were 4.99±1.33 for patients of group I and 10.47±10.62 for controls , ( p=0.023 ) . None of the adverse events or deaths occurred , were judged as likely to be related to the vitamin E supplementation . Conclusion Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity Objectives Chemotherapy-induced peripheral neuropathy is frequently a dose-limiting factor in cancer treatment and may cause pain and irreversible function loss in cancer survivors . We tested whether alpha-lipoic acid ( ALA ) could decrease the severity of peripheral neuropathy symptoms in patients undergoing platinum-based chemotherapy . Methods Cancer patients 18 years or older were r and omly selected to receive either 600 mg ALA or a placebo three times a day orally for 24 weeks while receiving chemotherapy regimens including cisplatin or oxaliplatin .  Neuropathy was measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity ( FACT/GOG-Ntx ) scale and the NCI Common Toxicity Criteria for Adverse Events neurotoxicity grade s. Results from timed functional tests and the Brief Pain Inventory ( BPI ) were secondary endpoints . Results Seventy of 243 ( 29 % ) patients completed the study ( 24 weeks ) . Both the ALA and the placebo arms had a comparable drop-out rate . No statistically significant differences were found between the ALA and the placebo groups for FACT/GOG-Ntx scores , BPI scores , and patients ' functional outcomes . Conclusion This strategy of oral ALA administration was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin . High attrition rates due to poor patient compliance and manner of dosage administration in this trial demonstrated a lack of feasibility for this intervention . Future studies to explore ALA as a neuroprotective agent should take heed of the barriers confronted in this study Purpose Oxaliplatin-induced peripheral neurotoxicity ( OPN ) is frequent and potentially severe , but successful treatment of this condition is still an unmet clinical need . We aim ed to determine whether treatment with goshajinkigan ( TJ-107 ) , a traditional Japanese medicine , is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with st and ard FOLFOX regimens . Methods In this phase 2 , r and omized , double-blind , placebo-controlled study , patients undergoing oxaliplatin-based chemotherapy were r and omized to receive either oral TJ-107 ( 7.5 g ) or matching placebo daily . The severity of OPN  was assessed according to the  Common Toxicity Criteria for Adverse Events at baseline , every 2 weeks until the 8th cycle , and every 4 weeks thereafter until the 26th week . The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy . Results Analyses were done by intention to treat . Eighty-nine patients were r and omly assigned to receive either TJ-107  ( n = 44 ) or placebo  ( n = 45 ) between May 2009 and March 2010 . The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups , respectively ( relative risk ( RR ) , 0.76 ; 95 % CI , 0.47–1.21 ) . The incidence of grade 3 OPN was 7 % ( TJ-107 ) vs. 13 % ( placebo ) ( 0.51 , 0.14–1.92 ) . No concerns regarding toxicity emerged with TJ-107 treatment . Conclusions TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy OBJECTIVES The present study was performed to determine the effect of 5 weeks of acupuncture treatment in a group setting on pain and symptoms of peripheral neuropathy in human immunodeficiency virus (HIV)infected individuals . DESIGN Twenty-one ( 21 ) subjects completed the study that consisted of a pretreatment and post-treatment case series design . The subjects completed the Pain Rating Scale and the Subjective Peripheral Neuropathy Screen ( SPNS ) before and after 5 weeks of acupuncture . The acupuncture treatments occurred two evenings per week . Each of the 10 sessions consisted of participants receiving 10 - 15 needle insertions in acupoints that addressed the individual 's changing pattern of pain , sleep problems , or other health issues . The treatment utilized only main or common points located below the elbows and knees , and on the head , neck , and ears . Only reactive points were used in the acupuncture treatments . Needles were left in situ for 30 - 45 minutes . RESULTS Comparison of the pretreatment and post-treatment Pain Rating Scale results indicated a significant reduction in present pain ( p = 0.0002 ) , least and most pain in the last 24 hours ( p < 0.0001 and p = 0.0004 , respectively ) and the total pain summary score ( p < 0.0001 ) . Symptoms reported in the SPNS were reduced during the 5 weeks of acupuncture . Scores for pain/aching/burning , pins and needles , and numbness in the h and s and feet were reduced ( all significant at less than p = 0.0065 ) , as well as the total summary score ( p = 0.0001 ) . CONCLUSION The results of this study indicate that subjective pain and symptoms of peripheral neuropathy were reduced during the period of individual acupuncture therapy delivered in a group setting . While the study design did not allow for control of nonspecific placebo factors , the data support the hypothesis that acupuncture in a group setting can reduce pain and neuropathic symptoms in HIV-infected individuals Purpose To gain insight into the association of physical activity ( PA ) , chemotherapy-induced peripheral neuropathy ( CIPN ) and health-related quality of life among colorectal cancer survivors , up to 11 years after diagnosis . Methods Data of the second data wave of a Dutch prospect i ve population -based survey among colorectal cancer survivors diagnosed between 2000 and 2009 as registered by the Eindhoven Cancer Registry was used . Eighty-three percent ( n = 1648 ) of patients filled out the  EORTC QLQ-C30  and the EORTC QLQ-CIPN20  of which 506 patients ( 31 % ) were treated with chemotherapy .  Results Treatment with chemotherapy was associated with a higher percentage of patients reporting CIPN symptoms regardless of PA . Furthermore , not meeting the Dutch PA guideline of 150 min of moderate to vigorous PA a week was associated with more CIPN among patients treated with chemotherapy . Also patients not treated with chemotherapy reported CIPN-like symptoms , especially when not meeting the PA guideline . Statistically significant and clinical ly relevant worse scores on almost all EORTC QLQ-C30 subscales were reported by those not meeting the PA guideline compared to those who did meet the guideline , regardless of CIPN symptoms . However , these differences were more pronounced in the group with many CIPN symptoms ( e.g. upper 30 % ) . Implication s for Cancer SurvivorsAlertness among health care professionals and patients for the importance of PA is warranted , as meeting the PA guideline was associated with less CIPN-like symptoms and a higher health-related quality of life regardless of treatment with chemotherapy Background Chemotherapy-induced peripheral neuropathy ( CIPN ) continues to be a substantial problem for many cancer patients . Pursuant to promising appearing pilot data , the current study evaluated the use of vitamin E for the prevention of CIPN . Methods A phase III , r and omized , double-blind , placebo-controlled study was conducted in patients undergoing therapy with neurotoxic chemotherapy , utilizing twice daily dosing of vitamin E ( 400 mg)/placebo . The primary endpoint was the incidence of grade 2 + sensory neuropathy ( SN ) toxicity ( CTCAE v 3.0 ) in each treatment arm , analyzed by chi-square testing . Planned sample size was 100 patients per arm to provide 80 % power to detect a difference in incidence of grade 2 + SN toxicity from 25 % in the placebo group to 10 % in the vitamin E group . Results Two-hundred seven patients were enrolled between December 1 , 2006 and December 14 , 2007 , producing 189 evaluable cases for analysis . Cytotoxic agents included taxanes ( 109 ) , cisplatin ( 8) , carboplatin ( 2 ) , oxaliplatin ( 50 ) , or combination ( 20 ) . There was no difference in the incidence of grade 2 + SN between the two arms ( 34%—vitamin E , 29%—placebo ; P = 0.43 ) . There were no significant differences between treatment arms for time to onset of neuropathy ( P = 0.58 ) , for chemotherapy dose reductions due to neuropathy ( P = 0.21 ) , or for secondary endpoints derived from patient-reported neuropathy symptom assessment s. The treatment was well tolerated overall . Conclusions Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival , grade 3–4 sensory neuropathy also increases . To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy , we did a pilot study . Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis ( N2 disease ) receiving adjuvant biweekly oxaliplatin ( 85 mg/m2 ) plus weekly fluorouracil boluses and low-dose leucovorin  were r and omized to oral N-acetylcysteine ( 1,200 mg ) ( arm A ) or placebo ( arm B ) . Clinical neurological and electrophysiological evaluations were performed at baseline and after 4 , 8 , and 12 treatment cycles . Treatment-related toxicity was evaluated based on National Cancer Institute ( NCI ) Criteria . After four cycles of chemotherapy , seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy . After eight cycles , five experienced sensory neuropathy ( grade 2–4 toxicity ) in arm B ; none in arm A ( p<0.05 ) . After 12 cycles , grade 2–4 sensory neuropathy was observed in eight patients in arm B , one in arm A ( p<0.05 ) . There were no significant electrophysiological changes in arm A after 4 , 8 , or 12 cycles of chemotherapy . We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy Background Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy . Calcium and magnesium ( Ca/Mg ) infusions are frequently used as preventatives , but a recent phase III trial failed to show that they prevent neurotoxicity . We therefore conducted a multicenter r and omized phase III trial to compare fluorouracil , leucovorin , and oxaliplatin ( mFOLFOX6 ) with and without Goshajinkigan ( GJG ) , a traditional Japanese herbal medicine ( Kampo ) , to determine GJG ’s potential for reducing peripheral neuropathy in patients with colorectal cancer . Methods Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6  were r and omly assigned to GJG ( 7.5 mg three times daily ) or placebo in a double-blind manner . The primary endpoint was the time to grade 2 or greater neuropathy , which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events ( NCI CTCAE ) . Findings An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued . One hundred eighty-two patients were evaluable for response . They included 89 patients in the GJG group and 93 patients in the placebo group . The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group . A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy ( hazard ratio , 1.908 ; p = 0.007 ) . Conclusion Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial . The clinical study was therefore terminated ABSTRACT Neuropathic pain is common among cancer patients and often difficult to treat . This study used Scrambler therapy , a patient-specific electrocutaneous nerve stimulation device , to treat cancer patients with pain . Patients received Scrambler therapy for 10 sessions ( one daily ) over a two-week period . The primary outcome was changed in pain numerical rating scale ( NRS ) at one month ; secondary outcomes were changes in the Brief Pain Inventory and European Organization for Treatment and Cancer QLC-CIPN-20(EORTC CIPN-20 ) , over time . Thirty-nine patients , mean age 56.5 yr , 16 men and 23 women , were treated over an 18-month period for an average of 9.3 days each . The “ now ” pain scores reduced from 6.6 before treatment to 4.5 at 14 days , 4.6 , 4.8 , and 4.6 at 1 , 2 , and 3 months , respectively ( p < 0.001 ) . Clinical ly important and statistically significant improvements were seen in average , least , and worst pain ; BPI interference with life scores , and motor and sensory scales on the EORTC CIPN-20 . No adverse effects were observed . In this single arm trial , Scrambler therapy appeared to relieve  cancer-associated chronic neuropathic pain both acutely and chronically , and provided sustained improvements in many indicators of quality of life PURPOSE We performed a r and omized , double-blind , placebo-controlled trial to assess the efficacy of glutathione ( GSH ) in the prevention of oxaliplatin-induced neurotoxicity . PATIENTS AND METHODS Fifty-two patients treated with a bimonthly oxaliplatin-based regimen  were r and omized to receive GSH ( 1,500 mg/m(2 ) over a 15-minute infusion period before oxaliplatin ) or normal saline solution .  Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four ( oxaliplatin dose , 400 mg/m(2 ) ) , eight ( oxaliplatin dose , 800 mg/m(2 ) ) , and 12 ( oxaliplatin dose , 1,200 mg/m(2 ) ) cycles of treatment . RESULTS At the fourth cycle , seven patients showed clinical ly evident neuropathy in the GSH arm , whereas 11 patients in the placebo arm did . After the eighth cycle , nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm . With regard to grade 2 to 4 National Cancer Institute common toxicity criteria , 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm ( P = .003 ) . After 12 cycles , grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm ( P = .004 ) . The neurophysiologic investigations ( sural sensory nerve conduction ) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm . The response rate was 26.9 % in the GSH arm and 23.1 % in the placebo arm , showing no reduction in activity of oxaliplatin . CONCLUSION This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy , and that it does not reduce the clinical activity of oxaliplatin OBJECTIVE To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction ( JHGWD ) in treating  neuro-sensory toxicity induced by oxaliplatin . METHODS A r and omized controlled self-crossover trial was performed . Thirty-one patients were r and omly divided into AB and BA groups . Patients in A cycle belonged to the treated group , who were treated with chemotherapy combined with oxaliplatin plus JHGWD . Patients in B cycle belonged to the control group and were treated with chemotherapy alone . The peripheral neuro-sensory toxicity was observed and analyzed . RESULTS The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin , which included hyperaesthesia , chill , anaesthesia in the extremities , electrified sensation , formication , foreign body sensation and pain that might be exacerbated by exposure to cold . Twenty patients ( 64.5 % ) suffered from neuro-sensory toxicity in the treated group and 27 cases ( 87.1 % ) in the control group . Symptoms were more serious and lasted longer in the control group than those in the treated group ( P < 0.01 ) . CONCLUSION JHGWD could prevent and reduce the occurrence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin OBJECTIVES Three series of studies investigated whether 1 ) glutamine deficiency occurs in tumor-bearing rats , 2 ) glutamine supplementation improves protein metabolism during chemotherapy in tumor-bearing rats , and 3 ) oral glutamine supplement improves systemic immune and gut-barrier function in patients with esophageal cancer receiving radiochemotherapy . METHODS In the animal studies , AH109A hepatoma cells or Yoshida sarcoma cells were inoculated into male Donryu rats to induce tumors . Glutamine production was measured by U-14C-glutamine infusion and the conversion of arginine to glutamine was measured by infusion of U-14C-arginine . The effect of glutamine on protein metabolism was investigated by 1 - 14C-leucine infusion . In the clinical study , 13 patients with esophageal cancer were r and omized into two groups , control and glutamine supplemented ( 30 g/d ) , for 4 wk . RESULTS Glutamine levels in plasma and skeletal muscle were decreased in tumor-bearing rats , although glutamine production and the conversion of arginine to glutamine were increased . Glutamine-supplemented total parenteral nutrition reduced whole-body protein breakdown rate during chemotherapy in tumor-bearing rats . Oral supplementation of glutamine to the patients with esophageal cancer enhanced lymphocyte mitogenic function and reduced permeability of the gut during radiochemotherapy . CONCLUSIONS Glutamine depletion in host tissues occurs in tumor-bearing rats . Glutamine supplementation can attenuate loss of protein in the muscle in tumor-bearing animals and protect immune and gut-barrier function during radiochemotherapy in patients with advanced cancer PURPOSE Cumulative sensory neurotoxicity ( sNT ) is the dose-limiting toxicity of oxaliplatin , which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant setting s. In a nonr and omized , retrospective study , intravenous ( IV ) calcium/magnesium ( Ca/Mg ) was associated with reduced oxaliplatin-induced sNT . METHODS Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil , leucovorin , and oxaliplatin ( FOLFOX )  were r and omly assigned to Ca/Mg ( 1 g calcium gluconate plus 1 g magnesium sulfate pre- and post-oxaliplatin ) or placebo , in a double-blinded manner . The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events ( NCI CTCAE ; version 3 ) criteria . An oxaliplatin-specific sNT scale and patient question naires were also used to assess sNT . After 104 of 300 planned patients were enrolled , the study was closed . This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy ; these data were subsequently found to be incorrect . RESULTS Overall , 102 patients were available for analysis . Ca/Mg decreased the incidence of chronic , cumulative , grade 2 or greater sNT , as measured by NCI CTCAE ( P = .038 ) and also by the oxaliplatin-specific sNT scale ( P = .018 ) . In addition , acute muscle spasms associated with oxaliplatin were significantly reduced ( P = .01 ) No effect on acute , cold-induced sNT was found . No substantial differences in adverse effects were noted between Ca/Mg and placebo . CONCLUSION Despite early termination and decreased statistical power , this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin ( FOLFOX ) or irinotecan plus 5-fluorouracil/leucovorin ( FOLFIRI ) has become a st and ard regimen for advanced or recurrent colorectal cancer . Numerous studies have reported that long-term use of FOLFOX or FOLFIRI leads to better survival for these patients . Thus , control of the toxicity of these drugs may be crucial to prolonging survival . Fucoidan is one of the major sulfated polysaccharides of brown seaweeds and exhibits a wide range of biological activities . In the present study , we analyzed the effect of fucoidan on suppressing the toxicity of anti-cancer drugs . A total of 20 patients with unresectable advanced or recurrent colorectal cancer scheduled to undergo treatment with FOLFOX or FOLFIRI  were r and omly allocated into a fucoidan treatment group ( n=10 ) and a control group without fucoidan treatment ( n=10 ) . Results showed that fucoidan regulated the occurrence of fatigue during chemotherapy . Chemotherapy with fucoidan was continued for a longer period than chemotherapy without fucoidan . Additionally , the survival of patients with fucoidan treatment was longer than that of patients without fucoidan , although the difference was not significant . Thus , fucoidan may enable the continuous administration of chemotherapeutic drugs for patients with unresectable advanced or recurrent colorectal cancer , and as a result , the prognosis of such patients is prolonged Forty-six diabetic patients with chronic painful peripheral neuropathy were treated with acupuncture analgesia to determine its efficacy and long-term effectiveness . Twenty-nine ( 63 % ) patients were already on st and ard medical treatment for painful neuropathy . Patients initially received up to six courses of classical acupuncture analgesia over a period of 10 weeks , using traditional Chinese Medicine acupuncture points .  Forty-four patients completed the study with 34 ( 77 % ) showing significant improvement in their primary and /or secondary symptoms ( P < 0.01 ) . These patients were followed up for a period of 18 - 52 weeks with 67 % were able to stop or reduce their medications significantly . During the follow-up period only eight ( 24 % ) patients required further acupuncture treatment . Although 34 ( 77 % ) patients noted significant improvement in their symptoms , only seven ( 21 % ) noted that their symptoms cleared completely . All the patients but one finished the full course of acupuncture treatment without reported or observed side effects . There were no significant changes either in the peripheral neurological examination scores , VPT or in HbA1c during the course of treatment . These data suggest that acupuncture is a safe and effective therapy for the long-term management of painful diabetic neuropathy , although its mechanism of action remains speculative OBJECTIVE To investigate why , in spite of a vast variety of treatment agents , the alleviation of pain in patients with diabetic neuropathy is difficult . Previous studies have not used a treatment algorithm based on anatomic site and neuropathophysiological source of the neuropathic pain . RESEARCH DESIGN AND METHODS A model that categorizes the types of pain into three groups ( superficial , deep , and muscular ) was applied in 75 diabetic patients with chronic ( > 12 mo ) painful distal symmetrical polyneuropathy in a controlled case series . Twenty-two patients were untreated and 53 patients were treated with imipramine ± mexiletine for deep pain , capsaicin for superficial pain , and stretching exercises and metaxalone ± piroxican for muscular pain . Each type of pain was scored separately on a scale of 0 ( none ) to 19 ( worst ) , and the total of all three types was used as an index of overall pain . Ability to sleep through the night was scored by a scale of 1 ( never ) to 5 ( always ) . RESULTS No significant differences were observed in initial pain scores , sleep scores , demographics , biochemistries , or physical findings between the two groups . After 3 mo a significant improvement in scores was noted in the treated but not the untreated patients . In addition , a significant difference was found in the change of scores between the treated and untreated patients : total pain ( −18 ± 2 vs. 0 ± 2 ) , deep pain ( −7 ± 1 vs. 0 ± 1 ) , superficial pain ( −5 ± 1 vs. 0 ± 1 ) , muscular pain ( −6 ± 1 vs. 0 ± 1 ) , and sleep ( 1.2 ± 0.2 vs. 0.2 ± 0.2 ) , all P < 0.0001 . In treated patients 21 % became pain-free ( total pain < 2 ) , 66 % had improvement ( decrease in total pain > 5 , but not total elimination of painful symptoms ) , and 13 % were considered treatment failures ( a decrease in total pain of < or = 5 ) . This compares with 0 ( P < 0.02 ) , 10 ( P < 0.0001 ) , and 90 % ( P < 0.0001 ) , respectively , in the untreated patients . CONCLUSIONS This study presents a new rationale and hypothesis for the successful treatment of chronic painful diabetic peripheral neuropathy . It uniquely bases the treatment algorithm on the types and sources of the pain PURPOSE The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy .  METHODS Between April 1999 and October 2000 , forty-seven patients were r and omly assigned to either group one , which received vitamin E supplementation during cisplatin chemotherapy , or to group two , which received cisplatin chemotherapy alone . Alpha-tocopherol ( vitamin E ; 300 mg/d ) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment . For pre clinical studies , nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E. RESULTS Twenty-seven patients completed six cycles of cisplatin chemotherapy : 13 patients in group one and 14 patients in group two . The incidence of neurotoxicity was significantly lower in group one ( 30.7 % ) than it was in group two ( 85.7 % ; P < .01 ) . The severity of neurotoxicity , measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters , was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E ( 2 v 4.7 , P < .01 ) . The results of the pre clinical studies showed that when cisplatin was combined with vitamin E , no differences were observed in tumor weight inhibition , tumor growth delay , or life span as compared with treatment with cisplatin alone . CONCLUSION Supplementation of patients receiving cisplatin chemotherapy  with vitamin E decreases the incidence and severity of peripheral neurotoxicity OBJECTIVE To observe the clinical effects of acupuncture for diabetic peripheral neuropathy . METHODS Totally 65 patients were r and omly divided into a treatment group of 32 cases and a control group of 33 cases . On the basis of conventional treatment of diabetes , acupuncture was used in the treatment group , and inositol was orally administered in the control group . During a 3-month treatment , changes in the symptoms were observed . RESULTS In the treatment group , 16 cases were markedly relieved , 12 cases improved , and 4 cases failed , with a total effective rate of 87.5 % . In the control group , 7 cases were markedly relieved , 14 cases improved and 12 cases failed , with a total effective rate of 63.6 % . There was a significant difference in the total effective rate between the 2 groups ( P < 0.05 ) . CONCLUSION Acupuncture may show good effects for diabetic peripheral neuropathy We introduce the current research on complementary and alternative medicine ( CAM ) in the West , which we refer to as Evidence -based CAM ( EBCAM ) , and discuss its characteristics , problems , and perspectives . Compared with the common attitude of CAM research ers in Japan , that of EBCAM research ers is more objective and often self-critical . EBCAM research is still developing because r and omized controlled trials on CAM have many method ological flaws . Caution should be employed in interpreting provisional conclusions of relevant systematic review s. CAM research ers in Japan should view the case report method from a perspective other than efficacy . Also , they will have to prepare evidence in response to dem and s from CAM consumers . Priority of research subjects from various kinds of CAM should be decided according to their popularity . Therefore , a large-scale survey on CAM use in Japan is essential Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin ( FOLFOX ) regimen has become the st and ard adjuvant treatment for colorectal cancer . However , the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy . Many strategies have been proposed in order to manage the neurotoxicity , but their effect on antitumoral efficacy is still unclear . In this study , we investigated the effect of reduced glutathione administration on neurotoxicity , oxaliplatin pharmacokinetics , and platinum-DNA ( Pt-DNA ) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen . Twenty-seven patients were r and omized to receive GSH 1500 mg/m2 or saline solution before oxaliplatin infusion . Evaluation of neurotoxicity , pharmacokinetics of plasmatic total and ultrafiltered Pt , and determination of Pt-DNA adduct formation on white blood cells was performed during the 5th , 9th , and 12th cycles . At the end of all cycles of therapy , the patients in the GSH arm showed a statistically significant reduction of neurotoxicity ( P=0.0037 ) compared with the placebo arm . There were no significant differences in the main pharmacokinetic parameters between the two arms except a lower area under the plasma concentration – time curve and a smaller apparent steady-state volume of distribution ( Vss ) when GSH was coadministered . This difference can be explained by the natural function of GSH in the detoxification of oxaliplatin and by its ability to remove the Pt bound to plasma proteins . The determination of Pt-DNA adduct formation shows no statistically significant differences between the two arms . In conclusion , this study indicates that coadministration of GSH is an effective strategy to reduce the oxaliplatin-induced neurotoxicity without impairing neither the pharmacokinetics of oxaliplatin , nor the Pt-DNA adduct formation
Background .
Chemotherapy-induced peripheral neuropathy ( CIPN ) is a common adverse effect of chemotherapy treatment in colorectal cancer ( CRC ) , negatively affecting the daily functioning and quality of life of CRC patients .
Currently , there are no established treatments to prevent or reduce CIPN .
The purpose of this systematic review was to identify lifestyle-related factors that can aid in preventing or reducing CIPN , as such factors may promote self-management options for CRC patients suffering from CIPN .