硫酸镁预防奥沙利铂神经毒性30例

2004年10月至2006年4月,我科用硫酸镁预防奥沙利铂（L—OHP）的神经毒性30例,效果良好,现小结如下。     

硫酸镁预防奥沙利铂神经毒性的临床观察

目的　观察硫酸镁对奥沙利铂引起的神经毒性的预防作用。方法　入选病例均须用包括奥沙利铂的化疗方案 ,随机分为 A、B两组。 A组 (试验组 )为硫酸镁 +化疗 ;B组 (对照组 )为单用化疗。 A组用奥沙利铂前加用2 5 %硫酸镁 4 m l加入 5 %葡萄糖液 5 0 0 ml中静脉滴注 ,每天 1次 ,连用 3天。完成 4个周期后评价疗效。结果　可评价疗效病例 4 5例 ,A组 2 2例 ,B组 2 3例。其中 A组发生 1级 2例 ,2级 1例 ,3、4级均 0例 ,总发生率 13.6 %。 B组发生 1级 9例 ,2级 3例 ,3级 1例 ,4级 0例 ,总发生率 5 6 .5 % ,两组差异有显著性 ( P<0 .0 5 )。结论　硫酸镁能降低奥沙利铂神经毒性的发生率 ,值得临床推广使用     

葡萄糖酸钙和硫酸镁预防奥沙利铂对晚期结直肠癌患者的神经毒性

[目的]观察静脉联合使用葡萄糖酸钙和硫酸镁预防晚期结直肠癌患者接受奥沙利铂治疗引起的神经毒性的疗效.[方法]入组120例结直肠腺癌患者,均接受含奥沙利铂的mFOLFOX6化疗方案.采用随机、对照的方法,将120例患者随机分为研究组和对照组,每组各60例.研究组自第1周期化疗起,在使用奥沙利铂治疗前后8h各使用1次10％葡萄糖酸钙针20ml,并加用25％硫酸镁针10ml.对照组单用化疗.分别于化疗后1～4个周期,评定神经毒性的发生率及严重程度,患者的体力状况按体力状况评分(KPS)标准来评估.[结果]在1～4个周期化疗结束后,研究组的神经毒性发生率明显低于对照组(P＜0.05);静脉使用钙镁制剂后,可降低奥沙利铂化疗过程中引起的神经毒性(P=0.043).但化疗前后两组患者的体力状况评分(KPS)、疗效均无统计学的差异.[结论]静脉使用葡萄糖酸钙和硫酸镁可预防奥沙利铂急性神经毒性,并可减少Ⅱ级或更高级慢性神经毒性的发生率.     

门冬氨酸钾镁与葡萄糖酸钙联用防治奥沙利铂神经毒性的临床观察

目的观察门冬氨酸钾镁联用葡萄糖酸钙防治奥沙利铂神经毒性的近期疗效。方法入选54例患者随机分为A、B两组,两组化疗方案均为含奥沙利铂130mg/m2的化疗方案,21天为1周期。A组(试验组)门冬氨酸钾镁 葡萄糖酸钙 化疗。B组(对照组)单用化疗。A组在用奥沙利铂之前加用5%葡萄糖溶液250ml 门冬氨酸钾镁20ml 10%葡萄糖酸钙20ml静点,第1~7天,所有患者完成4周期化疗后评价疗效。结果可评价病例54例,A组28例,发生神经毒性1级5例;2级2例;3级1例,总发生率28.5%。B组26例,发生神经毒性1级9例;2级4例;3级3例,总发生率61.5%。两组有显著性差异(P<0.01)。结论门冬氨酸钾镁与葡萄糖酸钙联用能降低奥沙利铂神经毒性的发生率,值得临床推广应用。     

延长奥沙利铂输注时间预防其外周神经毒性的临床研究

目的:在胃肠道肿瘤患者应用奥沙利铂+亚叶酸钙+氟尿嘧啶(FOLFOX方案)化疗后,观察延长奥沙利铂输注时间对其外周神经毒性的预防作用。方法:98例肿瘤患者随机分为三组,A组在使用奥沙利铂时将滴注时间延长至6小时;B组延长至4小时;C组奥沙利铂滴注时间为2小时。在化疗6周期及化疗12周期后分别比较三组神经毒性的总发生率及外周神经毒性级别。结果:6周期化疗后A组神经毒性的总发生率明显低于C组(P=0.0003);B组神经毒性的总发生率亦低于C组(P=0.034); A组神经毒性发生率低于B组(P=0.027),均具有统计学意义。12周期化疗后A组神经毒性的总发生率明显低于C组(P=0.002);B组神经毒性的总发生率亦低于C组(P=0.025);而A组和B组之间比较无统计学差异(P=0.371)。结论:使用奥沙利铂时将滴注时间延长至4-6小时可以有效减少神经毒性发生。     

谷胱甘肽预防奥沙利铂神经毒性的疗效观察

目的:评价谷胱甘肽对奥沙利铂神经毒性的防治疗效[1]。方法:87例奥沙利铂全身化疗的肿瘤患者随机分为2组,治疗组44例(男性36例,女性8例),年龄为22-75岁,平均年龄为48岁;对照组43例(男性35例,女性8例),年龄为19-70岁,平均年龄为45岁。治疗组奥沙利铂化疗前2天,使用谷胱甘肽1200mg加入5%GS 250ml,静滴,每日一次,至化疗结束后3-5天;对照组予以保肝对症治疗,不使用谷胱甘肽。结果:治疗组奥沙利铂神经毒性发生率11.36%(5/44),对照组为51.16%(22/43),治疗组与对照组比较,差异有统计学意义(P<0.05)。结论:谷胱甘肽对预防奥沙利铂的神经毒性有较好效果,值得临床推行。     

钙镁制剂和谷胱甘肽预防奥沙利铂所致神经毒性的效果观察

目的 评价钙镁制剂和谷胱甘肽(GSH)对奥沙利铂(OXL)引起的神经毒性的预防作用.方法 采用随机、双盲、安慰剂对照的方法,将接受FOLFOX4方案化疗的93例肿瘤患者随机分为3组,在化疗的同时分别给予钙镁制剂(29例)、GSH(33例)和生理盐水(3l例),观察每组神经毒性的发生率、严重程度以及患者的体力状况.结果 钙镁制剂组、GSH组和单纯化疗组急性神经毒性的发生率分别为82.8%、90.9%和93.5%,差异无统计学意义(均P>0.05).慢性神经毒性方面,化疗3个周期时,钙镁制剂组、GSH组和单纯化疗组1～2度神经毒性的发生率分别为37.9%、48.5%和42.0%,无3度神经毒性发生;化疗6个周期时,1～2度神经毒性的发生率分别为68.2%、88.9%和85.2%,5例患者出现3度神经毒性;化疗9个周期时,1～2度神经毒性的发生率分别为81.3%、90.0%和92.9%,又有2例出现3度神经毒性.3组1～2度神经毒性的发生率差异均无统计学意义(均P>0.05).化疗后,3组患者的美国东部肿瘤协作组(ECOG)评分变化相似,差异无统计学意义(P>0.05).结论 钙镁制剂和GSH对奥沙利铂引起的神经毒性无明显预防作用.     

奥沙利铂神经毒性防治研究进展

奥沙利铂（oxaliplatin,OXA）是继顺铂（cisplatin,DDP）和卡铂（carboplatin,CBP）后第3代铂类药物,具有抗癌活性高、抗瘤谱广等特点,目前广泛应用于胃肠道肿瘤、头颈部肿瘤、卵巢癌、淋巴瘤等常见肿瘤的治疗中,应用前景较好。但其周围神经毒性呈剂量限制性和依赖性,常导致可逆的蓄积性外周感觉神经病变。     

钙镁合剂预防奥沙利铂所致神经毒性的系统评价和Meta分析

  目的  评价静脉钙镁合剂对奥沙利铂所致的神经毒性的预防作用。   方法   查找使用奥沙利铂为基础的化疗方案, 并对比钙镁合剂和安慰剂预防神经毒性的随机对照研究。采用随机或者固定效应模型对资料进行Meta分析。   结果  共纳入16个临床研究, 981例患者。Meta分析显示钙镁合剂较安慰剂在预防奥沙利铂所致神经毒性上差异有统计学意义, 包括神经毒性的发生(P < 0.000 01)和 > I度的神经毒性(P < 0.000 01)。亚组分析表明: 钙镁至少均 > 1 g的合剂对预防奥沙利铂所致神经毒性有效。钙镁合剂与谷胱甘肽联合使用与安慰剂相比差异有统计学意义。   结论   钙镁合剂能有效预防奥沙利铂所致神经毒性, 与谷胱甘肽联合可能增加疗效。      

当归四逆汤加味联合钙镁合剂预防奥沙利铂神经毒性的临床观察

目的观察当归四逆汤加味联合钙镁合剂预防奥沙利铂外周神经毒性的疗效。方法49例接受奥沙利铂、5-氟脲嘧啶、亚叶酸钙治疗的胃肠道肿瘤患者，治疗组接受当归四逆汤加味联合钙镁合剂，对照组单纯接受钙镁合剂预防治疗。结果4周期后，治疗组出现临床神经毒性5例，而对照组11例，差异有统计学意义（P〈0．05）。结论预防性应用当归四逆汤加味联合钙镁合剂能降低奥沙利铂神经毒性的发生率。     

Reduction of oxaliplatin-related neurotoxicity by calcium and magnesium infusions

PURPOSE: Oxaliplatin in combination with infusional 5-fluorouracil/leucovorin (FOLFOX) have emerged as the standard of care in the therapy of advanced-stage colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. We decided to use Ca and Mg for prevention of oxaliplatin-related neurotoxicity with reference to the report of Gamelin et al. METHODS: The subjects were 14 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m(2)) was given intravenously as FOLFOX regimen. All 14 patients received infusions of Ca gluconate and Mg sulfate before and after oxaliplatin. RESULTS: Only 1 patient had grade 3 toxicity (nausea and vomiting). Sensory neuropathy occurred in 8 patients (57.1%). There was no neurotoxicity with functional impairment in this study. Sensory neuropathy hardly occurred before 4 cycles. CONCLUSIONS: Ca/Mg infusions seem to prevent acute oxaliplatin-induced neurotoxic.     

草酸铂神经毒性的防治

目的评价卡马西平、葡萄糖酸钙防治草酸铂神经毒性的疗效.方法草酸铂130 mg/m2,静滴,第1天;醛氢叶酸(CF)200 mg/m2,静滴,第1～5天;5-Fu 300 mg/m2,静滴,第1～5天.21 d为1周期.60例大肠癌患者随机分成3组,每组20例.分别观察卡马西平组(A组)、葡萄糖酸钙防治组(B组)、对照组(C组)的草酸铂神经毒性.结果 A组、B组、C组的草酸铂神经毒性发生率分别为45.0%、50.0%和85.0%.A组神经毒性Ⅰ级9例,B组神经毒性Ⅰ级9例、Ⅱ级1例,C组神经毒性1级14例、Ⅱ级2例、Ⅲ级1例,其中C组3例累积剂量神经毒性用卡马西平治疗缓解,平均累积剂量A、 B、 C组分别为720 mg/m2、650 mg/m2和480 mg/m2,A、B组与C组的神经毒性发生率比较差异有显著性(P＜0.05).结论卡马西平、葡萄糖酸钙可以减少草酸铂的神经毒性发生,缓解神经毒性症状,增加累积剂量,值得进一步研究.     

奥沙利铂过敏的临床特征分析

目的探索奥沙利铂过敏的发生率和临床特征。方法收集2008年3月至2012年12月期间曾接受至少1次奥沙利铂治疗的194例患者的临床资料,分析奥沙利铂过敏的临床特征。结果 194例患者中,21例(10.8%)发生过敏反应,其中3⁴度过敏发生率为4.6%。过敏最常发生于第74度过敏发生率为4.6%。过敏最常发生于第7⁸个周期,发生率为7.3%。延迟性发热是最常见的过敏症状;以呼吸和循环系统症状为主要过敏表现者,症状发生最快、程度最严重。结论中国患者奥沙利铂过敏发生率与西方人群或其他亚洲人群类似。第78个周期,发生率为7.3%。延迟性发热是最常见的过敏症状;以呼吸和循环系统症状为主要过敏表现者,症状发生最快、程度最严重。结论中国患者奥沙利铂过敏发生率与西方人群或其他亚洲人群类似。第7⁸个周期过敏发生率最高,严重过敏多发生在输注开始前10 min,提醒临床医生在此期间密切关注。     

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

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.

Materials and methods

Seven hundred and fifty five previously untreated ACC patients were randomised 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.     

Infusion of calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in colorectal cancer: a systematic review and meta-analysis

BackgroundIt is hypothesised that infusion of calcium and magnesium (Ca/Mg) can reduce the occurrence of oxaliplatin-related sensory neurotoxicity. However, more recent data have drawn a controversial picture concerning this topic.MethodsA comprehensive literature search was performed using Medline, Embase, Cochrane Library and Google Scholar database up to 1st August 2011. Keywords for the search were: calcium, magnesium and oxaliplatin. The odd ratio (OR) for neurotoxicity and relative risk (RR) for tumour response rate were calculated.ResultsSeven studies (four randomised controlled trials (RCTs) and three cohorts) including a total of 1238 participants met our criteria. Meta-analysis of three RCT studies that reported in National Cancer Institute-Common Toxicity Criteria (NCE-CTC) showed that OR for neurotoxicity of Grade ⩾2 was not significant (OR 0.47; 95% confidence interval (CI) 0.22–1.00, P homogeneity = .729). The OR was also not significant in All Grades (OR 3.15, 0.32–31.35, P homogeneity = .952) and Grade 3 subgroup (OR 1.64, 0.30–9.00, P homogeneity = .656). No statistically significant difference was observed in RR for tumour response rate. (RR = 0.91, 0.78–1.06, P homogeneity = .33)ConclusionsThis meta-analysis does not support the hypothesis that infusion of Ca/Mg reduces the occurrence of neurotoxicity in oxaliplatin-treated patients with colorectal cancer measuring with NCE-CTC criteria. On the other hand, our results support the hypothesis that administrations of Ca/Mg do not impair the efficacy of oxaliplatin-based chemotherapy. However, large-scale randomised, controlled clinical trials will be required to confirm these hypotheses.     

Use of calcium and magnesium infusions in prevention of oxaliplatin induced sensory neuropathy

Aim: Oxaliplatin‐related neurotoxicity is frequently dose‐limiting. Following retrospective studies suggesting neuroprotective effects of calcium and magnesium (Ca and Mg), we conducted a prospective study using nerve conduction studies (NCS) to evaluate the effectiveness of such infusions in oxaliplatin‐related neuropathy. Methods: Colorectal cancer patients receiving FOLFOX‐4 or capecitabine plus oxaliplatin were randomized to (Arm A) calcium gluconate 1g +15% magnesium sulphate 1g diluted in 100 mL of dextrose 5% or (Arm B) placebo. Neuropathy was assessed using the National Cancer Center common toxicity criteria, oxaliplatin‐specific scale and NCS. Results: This study was terminated prematurely based on the initial negative results of the CONcePT trial. Median follow up was 8.7 months. Overall 22 out of 27 patients experienced neuropathy. The subjective neuropathy rate was 77% in Arm A and 86% in Arm B, (P = 0.6). At the end of treatment, three patients in Arm A and 0 in Arm B had grade 3 numbness (P = 0.09). There was no significant difference in neuropathy between arms, whether during or at the end of treatment. Median objective neuropathy score was 6 in Arm A and 0 in Arm B, (P = 0.02). Conclusion: Premature closure of this study limits the interpretation of results. While there was a trend towards reduced subjective acute sensory neuropathy with Ca and Mg, this was not significant. Ca and Mg failed to reduce the rate of cumulative sensory neuropathy and instead increased the rate of abnormal NCS, suggesting a significant difference in perceived sensory and objective neuropathy.     

钙镁输液预防奥沙利铂神经毒性的作用:一个Ⅲ期试验(英文)

Objective:This study is a prospective randomized, double-blind, placebo-controlled study to evaluate the effect of calcium and magnesium (Ca/Mg) infusion on amelioration of oxaliplatin neuropathy, the dose-limiting toxicity. Methods:Sixty patients with resected colorectal carcinoma (CRC) planned to receive adjuvant oxaliplatin-containing regimen were randomly assigned to two arms; Arm A:patients received Ca/Mg were given as 1 gm Ca gluconate and 1 gm MgSO 4 in 250 mL of intravenous (IV) solution over 30 min pre and post oxaliplatin infusion, and Arm B:patients received 250 mL of IV solution without Ca/Mg over 30 min pre and post oxaliplatin infusion. Primary outcome was to assess percentage of patients with oxaliplatin-induced neurotoxicity. Neurotoxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0. Results:Sixty patients in both arms were assessed, 30 with Ca/Mg infusion and 30 without. Patients developed neurotoxicity in arm A were significantly lower than that in arm B after the end of treatment; 7 (23.3%) and 14 (46.6%) respectively (P < 0.05), and significantly lower duration of neuropathy in months (8 ± 2.5 vs 18 ± 3) respectively (P < 0.001). Conclusion:Use of IV Ca/Mg showed a statistically significant reduction of peripheral neuropathy (PN) in patients with CRC receiving oxaliplatin in the adjuvant settings.     

国产奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的临床观察

目的评价奥沙利铂(L-OHP)联合氟尿嘧啶(5-Fu)、亚叶酸钙(CF)方案治疗晚期结直肠癌的疗效与毒副反应.方法奥沙利铂130 mg/m2,静滴4 h,第1天;亚叶酸钙200 mg静脉滴注2 h,5-Fu 300 mg/m2,持续静滴6～8 h,第1～5天(亚叶酸钙滴完后用);21 d为1周期,行2周期治疗后评价疗效.结果全组完全缓解(CR)1例,部分缓解(PR)12例,总有效率(CR PR)为43.3%.毒性反应以骨髓抑制、感觉性神经毒性为主,多为Ⅰ～Ⅱ度,其中白细胞减少发生率为46.7%,感觉性神经毒性发生率为77.7%,无化疗相关死亡.结论奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期结直肠癌疗效肯定,毒副反应能耐受.     

地塞米松联合硫酸镁预防长春瑞滨所致静脉炎

目的　长春瑞滨是目前最常用的化疗药物之一,它是缓和的发疱剂,能引起静脉炎。本研究旨在探讨地塞米松联合硫酸镁预防长春瑞滨所致静脉炎的效果。方法　前瞻性观察我科３００例初治晚期非小细胞肺癌患者,化疗方案包含长春瑞滨,每周期评估静脉炎的程度。全组分为试验组和对照组各１５０例,试验组使用长春瑞滨前后用地塞米松２.５ｍｇ静脉注射,５０％硫酸镁湿敷静脉穿刺点以上皮肤,从静脉用药前１０ｍｉｎ至结束后４～６ｈ;对照组仅用药前后给予地塞米松２.５ｍｇ静脉注射,未用硫酸镁湿敷。结果　试验组静脉注射长春瑞滨７９１次,其中３９次（４.９３％）发生静脉炎;对照组予８０７次静脉注射长春瑞滨,９８次（１２.１４％）发生静脉炎,两组差异有统计学意义（Ｐ＜０.０５）。试验组有８例发生静脉炎（５.３３％）,对照组１９例发生静脉炎（１２.６７％）,两组差异有统计学意义（Ｐ＜０.０５）。结论　地塞米松联合硫酸镁能预防长春瑞滨治疗非小细胞肺癌患者所致静脉炎的发生,增加患者对化疗的依从性。