***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: 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 Objective . This clinical trial was design ed to investigate whether goshajinkigan reduces the onset of diabetic complications or not . Material s and Methods . A total of 332 type 2 diabetic mellitus patients were registered from 9 clinical centers from March 2000 to August 2007 . Patients were r and omly assigned to take goshajinkigan extract powder , 2.5 grams for 3 times a day or no kampo therapy , additionally to the regular treatment . The primary endpoints were the onset of macrovascular diseases or progression of nephropathy or retinopathy . Statistical analysis was performed by the intention-to-treat method . Results . After 5 years of observation , 116 patients were su bmi tted to analysis . Among them , no macrovascular events were observed in both groups . Although 43 participants had upstaging of retinopathy or nephropathy in total , there was no significant difference between goshajinkigan group and control group . Deterioration of ankle reflex was suppressed in goshajinkigan group . Also glycated hemoglobin , and fasting plasma glucose were decreased in the goshajinkigan group . Conclusion . Although the power of analysis was too low to demonstrate any effects of goshajinkigan on the progression of macrovascular diseases , retinopathy or nephropathy , goshajinkigan may be beneficial for diabetic neuropathy and glycemic control Oxaliplatin , a widely used chemotherapeutic agent , induces peripheral neuropathy that manifests itself as two distinct phases : acute cold hyperesthesia and chronic peripheral hypoesthesia/dysesthesia . The latter is a serious dose-limiting side effect that can often lead to withdrawal of treatment . We have developed a rat model expressing both phases and used the model to investigate the action of goshajinkigan ( GJG ) , a traditional Japanese herbal medicine , which was reported to ameliorate oxaliplatin-induced neuropathy in a placebo-controlled double-blind r and omized phase II study . In this study , neuropathy was induced by injection of oxaliplatin twice weekly for 8 wks . The maximum level of cold hyperesthesia was observed at 4 wks with heat hypoesthesia developing later . Microscopy studies revealed atrophy of axons of myelinated sciatic nerve fibers in oxaliplatin-treated rats at 8 wks . Co-administration of GJG  ameliorated both abnormal sensations as well as histological damage to the sciatic nerve . A pharmacokinetic study revealed numerous neuroprotective components of GJG that are rapidly absorbed into the blood . GJG and some of its components attenuated the generation of oxaliplatin-induced reactive oxygen species , which is a possible mechanism of oxaliplatin-induced neurotoxicity . The present study provides a useful animal model for oxaliplatin-induced neurotoxicity as well as a promising prophylactic agent 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 CONTEXT Most medical interventions have modest effects , but occasionally some clinical trials may find very large effects for benefits or harms . OBJECTIVE To evaluate the frequency and features of very large effects in medicine . DATA SOURCES Cochrane Data base of Systematic Review s ( CDSR , 2010 , issue 7 ) . STUDY SELECTION We separated all binary- outcome CDSR forest plots with comparisons of interventions according to whether the first published trial , a subsequent trial ( not the first ) , or no trial had a nominally statistically significant ( P < .05 ) very large effect ( odds ratio [ OR ] , ≥5 ) . We also sample d r and omly 250 topics from each group for further in-depth evaluation . DATA EXTRACTION We assessed the types of treatments and outcomes in trials with very large effects , examined how often large-effect trials were followed up by other trials on the same topic , and how these effects compared against the effects of the respective meta-analyses . RESULTS Among 85,002 forest plots ( from 3082 review s ) , 8239 ( 9.7 % ) had a significant very large effect in the first published trial , 5158 ( 6.1 % ) only after the first published trial , and 71,605 ( 84.2 % ) had no trials with significant very large effects . Nominally significant very large effects typically appeared in small trials with median number of events : 18 in first trials and 15 in subsequent trials . Topics with very large effects were less likely than other topics to address mortality ( 3.6 % in first trials , 3.2 % in subsequent trials , and 11.6 % in no trials with significant very large effects ) and were more likely to address laboratory-defined efficacy ( 10 % in first trials,10.8 % in subsequent , and 3.2 % in no trials with significant very large effects ) . First trials with very large effects were as likely as trials with no very large effects to have subsequent published trials . Ninety percent and 98 % of the very large effects observed in first and subsequently published trials , respectively , became smaller in meta-analyses that included other trials ; the median odds ratio decreased from 11.88 to 4.20 for first trials , and from 10.02 to 2.60 for subsequent trials . For 46 of the 500 selected topics ( 9.2 % ; first and subsequent trials ) with a very large-effect trial , the meta- analysis maintained very large effects with P < .001 when additional trials were included , but none pertained to mortality-related outcomes . Across the whole CDSR , there was only 1 intervention with large beneficial effects on mortality , P < .001 , and no major concerns about the quality of the evidence ( for a trial on extracorporeal oxygenation for severe respiratory failure in newborns ) . CONCLUSIONS Most large treatment effects emerge from small studies , and when additional trials are performed , the effect sizes become typically much smaller . Well-vali date d large effects are uncommon and pertain to nonfatal outcomes Goshajinkigan , a herbal medicine , has long been used in Japan to alleviate the subjective symptoms of diabetic neuropathy ; however , its effects have not been confirmed objective ly . We evaluated its effects on subjective symptoms and on vibration sensation in patients with diabetic neuropathy . The oral administration of 7.5 g/day of Goshajinkigan for 3 months ( treatment period ) relieved subjective symptoms of numbness in 9 of 13 patients . When the drug was discontinued for 2 months as a washout period , the subjective symptom worsened in 7 of 13 patients . Chi-square analysis revealed significant effects of Goshajiniagan on subjective symptoms ( P < 0.001 for numbness and P < 0.05 for cold sensation ) . Vibration sensation was evaluated by measuring vibratory threshold using an SMV-5 vibrometer . There were significant changes in vibratory thresholds by paired t-test ( P < 0.05 ) both in the upper and the lower extremities during the treatment and washout periods . Chi-square analysis also revealed a significant effect of Goshajinkigan on vibratory threshold ( P < 0.01 ) . There was no significant change in glycosylated hemoglobin as a whole during the study . These observations confirm that Goshajinkigan relieves subjective symptoms and demonstrate that it improves vibration sensation in patients with diabetic neuropathy BACKGROUND Goshajinkigan ( GJG ) is used for the treatment of several neurological symptoms . We investigated the efficacy of GJG and mecobalamin ( B12 ) against neurotoxicity associated with docetaxel ( DOC ) in breast cancer patients . MATERIAL S AND METHODS Sixty breast cancer patients were treated with DOC . Thirty-three patients ( GJG group ) received oral administration of 7.5 g/day GJG and 27 patients ( B12 group ) received oral administration of 1500 μg/day B12 .  Neuropathy was evaluated according to DEB-NTC ( Neurotoxicity Criteria of Debiopharm ) , Common Terminology Criteria for Adverse Events ( NCI-CTC ) ver . 3.0 , and a visual analogue scale ( VAS ) . This study employed a r and omized open design . RESULTS The incidence of neuropathy was 39.3 % in the GJG group , and 88.9 % in the B12 group ( p<0.01 ) . In the GJG group , grade 1 DEB-NTC was observed in 2 cases , grade 2 in 5 cases and grade 3 in 5 cases . Grade 1 NCI-CTC was observed in 7 cases , grade 2 in 6 cases , and VAS was 2.7 ± 2.2 . In the B12 group , grade s 1 , 2 and 3 DEB-NTC were observed in one case , 12 cases and 12 cases , respectively ; and grade s 1 , 2 and 3 NCI-CTC were observed in 11 cases , 12 cases and one case , and VAS was 4.9 ± 2.4 . CONCLUSIONS Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen Paclitaxel/carboplatin chemotherapy for cancer ( TC therapy ) exhibits neurotoxicity and causes peripheral neuropathy at a high frequency , which is difficult to cope with . In this study , we investigated the efficacy of Goshajinkigan , a traditional Japanese herbal medicine , for TC therapy-induced peripheral neuropathy . The subjects included in our study were patients with ovarian or endometrial cancer who underwent TC therapy and developed peripheral neuropathy . The patients were r and omly divided into Group A , comprising of 14 patients ( vitamin B12 treatment )  , and Group B , comprising of 15 patients ( vitamin B12 + Goshajinkigan treatment ) . The observation period was  
    Output:
    
Conclusions Goshajinkigan is unlikely to prevent CIPN in patients undergoing neurotoxic chemotherapy .