Adjuvant chemotherapy for colon cancer: the difference between Japanese and western strategies

Introduction: Colorectal cancer (CRC) is the third most common cancer in the western world and also in Japan. The key factors in curing CRC are early detection, surgery and adequate adjuvant chemotherapy if needed.

Areas covered: Based on the results of following pivotal adjuvant trials, FOLFOX or XELOX are considered standard adjuvant chemotherapy for patients with stage III colon cancer in the western countries. On the other hand, 5-FU based monotherapies showed favorable results as adjuvant chemotherapy in Japan providing comparable results to doublet strategies in the western countries. There are two key factors that could provide better outcome: D3 lymph node dissection (LND) and thorough pathological examinations.

Expert opinion: I believe that oxaliplatin based adjuvant chemotherapy may not be suitable for at least substage IIIA patients who underwent D3 surgery and were diagnosed by thorough pathological examinations for the following two reasons: toxicities and strongly stage-dependent added benefit of oxaliplatin in overall survival. We are awaiting the final results of three Japanese ongoing trials focusing on oxaliplatin based adjuvant chemotherapy. These results will hopefully help us create and implement global guidelines for truly standardizing the management of colon cancer prevalent all over the world, and help physicians recommend the treatment strategy available to each patient.     

Oxaliplatin: a review of its use in combination therapy for advanced metastatic colorectal cancer

Oxaliplatin (Eloxatin) is the only platinum compound to show clinical activity in colorectal cancer. The efficacy of a combination of oxaliplatin with various schedules of fluorouracil (5-FU)/folinic acid (FA) as first- or second-line treatment for advanced metastatic colorectal cancer has been investigated in large phase III trials. FOLFOX4 (an oxaliplatin/5-FU/FA regimen) as first-line therapy (n = 795) was superior to irinotecan/5-FU/FA (IFL). Response rates were 45% vs 31%, and median progression-free survival duration was 8.7 vs 6.9 months. The survival advantage shown by FOLFOX4 over the irinotecan combination (median survival duration 19.5 vs 14.8 months) may be confounded by differences in post-study treatment but equivalent efficacy is supported by another phase III trial of oxaliplatin and irinotecan combinations. As first-line therapy, oxaliplatin added to various 5-FU/FA regimens more than doubled the response rates from 16-22.6% to 48.3-53% and the median duration of progression-free survival was significantly longer with oxaliplatin/5-FU/FA than 5-FU/FA alone (7.9-9 versus 5.3-6.2 months, respectively).In disease resistant to irinotecan-based therapies, the oxaliplatin (FOLFOX4) regimen had superior efficacy to 5-FU/FA alone in a pivotal phase III trial (n = 816). Response rates and median durations of progression-free survival were 9.6% vs 0.7% and 5.6 vs 2.6 months, respectively. An oxaliplatin-induced cumulative peripheral sensory neuropathy (evident when total dose reaches approximate, equals 800 mg/m(2)) is dose limiting. The most frequently occurring grade 3 or 4 toxicities in oxaliplatin/5-FU/FA-recipients were neutropenia (up to 48%) and neurological toxicities (up to 18%). Gastrointestinal effects (diarrhoea [ approximate, equals 12%], nausea, vomiting, or mucositis/stomatitis [up to 6%]) are manageable. Withdrawals from oxaliplatin treatment were due to neuropathy (up to 10%), diarrhoea and/or vomiting (1%) or cutaneous toxicity (1%). Conclusion: As first-line therapy for metastatic colorectal cancer, oxaliplatin with 5-FU/FA consistently improves response rates and progression-free survival compared with various regimens of 5-FU/FA alone. The significant survival advantage shown by oxaliplatin/5-FU/FA (FOLFOX4) compared with first-line therapy with irinotecan/5-FU/FA (IFL) is encouraging but may require further confirmation. Oxaliplatin/5-FU/FA produces a significantly higher response rate and longer progression-free survival than 5-FU/FA in patients failing irinotecan-based therapies, and as such is also a useful second-line treatment. Although cumulative neurotoxicity is dose limiting, oxaliplatin has a manageable tolerability profile. Oxaliplatin as first- or second-line therapy is a valuable addition to the limited, but expanding, armamentarium of cytotoxic agents useful in advanced metastatic colorectal cancer.     

Severe disabling sensory-motor polyneuropathy during oxaliplatin-based chemotherapy

Oxaliplatin-based combination chemotherapy is an option for first-line therapy of metastatic colorectal cancer. It is associated with acute hyperexcitability of motor and sensory nerves, and a cumulative sensory axonal neuropathy. We describe a 56-year-old male with metastatic colorectal cancer treated with oxaliplatin and capecitabine who developed a rapidly ascending motor and sensory neuropathy, which rendered him wheelchair-bound. Heightened clinical suspicion for possible oxaliplatin-induced motor neuropathies may be warranted.     

神经节苷脂预防奥沙利铂致末梢神经毒性30例临床研究

目的观察神经节苷脂预防奥沙利铂致末梢神经毒性的疗效。方法将接受FOLFOX6方案的患者随机分为3组,即神经节苷脂组、钙镁合剂组及单纯化疗组。利用奥沙利铂专用神经毒性分级标准观察其神经毒性发生率及严重程度。结果神经节苷脂组、钙镁合剂组及单纯化疗组急性神经毒性发生率分别为64.28%,66.67%,92.59%,差异有统计学意义（P〈0.05）。化疗4周期和8周期时3组慢性神经毒性发生率差异有统计学意义（P〈0.05）;神经节苷脂组和钙镁合剂组Ⅰ-Ⅲ度神经毒性均低于单纯化疗组（P〉0.05）,神经节苷脂组和钙镁合剂组差异无统计学意义（P〉0.05）。结论应用神经节苷脂可有效预防或减少奥沙利铂神经毒性的发生率及损害程度。     

Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management

Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy. Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the risk of neurotoxicity. Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. In this article we describe the neurological adverse effects of the most commonly used chemotherapeutic agents.The vinca-alkaloids, cisplatin and the taxanes are amongst the most important drugs inducing peripheral neurotoxicity. These drugs are widely used for various malignancies such as ovarian and breast cancer, and haematological cancers. Chemotherapy-induced neuropathy is clearly related to cumulative dose or dose-intensities. Patients who already have neuropathic symptoms due to diabetes mellitus, hereditary neuropathies or earlier treatment with neurotoxic chemotherapy are thought to be more vulnerable for the development of chemotherapy-induced peripheral neuropathy. Methotrexate, cytarabine (cytosine arabinoside) and ifosfamide are primarily known for their central neurotoxic side effects. Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising cognitive deficits, hemiparesis, aphasia and progressive dementia. Risk factors are high doses, frequent administration and radiotherapy preceding methotrexate chemotherapy, which appears to be more neurotoxic than methotrexate as single modality. Data on management and neuroprotective agents are discussed. Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients who are at higher risk to develop neurotoxic side effects. None of the neuroprotective agents described in this article can be recommended for standard use in daily practise at this moment, and further studies are needed to confirm some of the beneficial effects described.     

卡培他滨联合奥沙利铂治疗晚期及复发性结肠癌的临床分析

目的观察卡培他滨联合奥沙利铂治疗晚期及复发性结肠癌的临床疗效及副作用。方法选择经病理证实的Ⅲ期和Ⅳ期晚期及复发性结肠癌患者36例,d1静脉滴注奥沙利铂130mg/m2;d1～14口服卡培他滨化疗2000mg/m2,分两次服用,早、晚饭后半小时各1次,1个治疗周期为3周,每位患者至少接受3个周期的化疗。结果经化疗达到CR的有7例,达到PR的有18例,达到SD的有9例,达到PD的有2例,总有效率为69.44%,中位缓解期为9.1个月,中位生存期为14.2个月,患者的毒副反应均较轻。结论卡培他滨联合奥沙利铂治疗晚期结肠癌疗效确切,不良反应小,值得推广应用。     

The pathophysiology of oxaliplatin-induced neurotoxicity

Nerve dysfunction is a common accompaniment of chemotherapy, typically occurring in a dose-dependent manner, so that the higher the dose and the longer the time of exposure, the more likely neuropathy is to occur. With the majority of chemotherapies, the mechanisms of neurotoxicity have not been clearly established. Cessation of therapy may prevent progression to a more severe syndrome and is often necessary even if there has been tumour response. Alternatively dose reduction may slow or halt progression. The clinical investigation of patients with suspected nerve dysfunction related to chemotherapy remains problematic. While routine nerve conduction studies can document the presence of a neuropathy, they do not provide further insight into pathophysiology. In contrast, measurements of nerve excitability by threshold tracking provide complementary information to conventional nerve conduction studies and may be used to infer the activity of a variety of ion channels, energy-dependent pumps and ion exchange processes activated during the process of impulse conduction. The present review will focus on recent developments in clinical rating scales and novel neurophysiological methods for the clinical investigation of chemotherapy-induced neurotoxicity, and will highlight how such methods may prove useful to study the neurological effects of chemotherapy. Specific emphasis will be placed on oxaliplatin, a platinum-based chemotherapy effective for colorectal cancer that exhibits dose-limiting neurotoxicity.     

还原型谷胱甘肽预防奥沙利铂慢性神经毒性的临床研究

目的评价还原型谷胱甘肽对奥沙利铂(OXA)引起的慢性神经毒性的预防作用。方法采用随机、对照的方法,将接受FOLFOX4方案辅助化疗的105例肿瘤患者随机分为治疗组和对照组,在化疗的同时分别给予还原型谷胱甘肽(54例)和生理盐水(51例),观察两组慢性神经毒性的发生率及严重程度。结果化疗2个周期时,两组的慢性神经毒性发生率分别是37.1%和41.1%,差异无统计学意义(P>0.05);化疗4个周期时,两组的慢性神经毒性发生率分别是58.5%和66.7%,差异无统计学意义(P>0.05);化疗6个周期时,两组的慢性神经毒性发生率分别是74.0%和89.7%,差异具有显著性统计学意义(P<0.05)。结论还原型谷胱甘肽是一种有效的预防奥沙利铂引起的慢性神经毒性的治疗措施,值得临床进一步推广应用。     

替吉奥联合奥沙利铂治疗晚期胃癌的临床疗效分析

目的观察替吉奥胶囊联合奥沙利铂治疗晚期胃癌的临床疗效。方法回顾分析44例晚期胃癌患者化疗资料,采用以下方案化疗:奥沙利铂130mg/m2,静脉滴注2h,d1;替吉奥胶囊口服30mg/m2,每日2次,dl~d14;21d为一个周期,完成2个周期。结果 44例患者完成化疗周期,其中PR 23例,sD 12例,PD 7例,RR 54.2%,DCR 81.7%。中位疾病进展时间为7.9个月,中位生存期为11.4个月。不良反应主要是胃肠道反应、骨髓抑制、外周神经毒性。结论替吉奥联合奥沙利铂治疗老年晚期胃癌患者耐受性好,有效率高,毒副反应低,值得临床推广。     

参麦注射液防治含奥沙利铂化疗方案所致神经毒性效果的临床观察

目的:观察参麦注射液防治含奥沙利铂化疗方案所致神经毒性的效果。方法:将96例应用含奥沙利铂化疗方案化疗的胃癌或大肠癌患者随机分为2组,试验组46例,对照组50例。试验组化疗前一天开始将参麦注射液50 mL加入5%葡萄糖注射液200 mL中静脉滴注,qd,连用14 d为1个周期。对照组不加用参麦注射液,单纯化疗。4个化疗周期(每个化疗周期21 d)后评价疗效,观察神经毒性反应的变化,并测定周围神经功能。结果:试验组神经毒性发生率32.6%(15/46),对照组为72.0%(36/50),2组比较差异有统计学意义(P<0.05)。周围神经功能测定,试验组和对照组腓神经感觉神经传导速度(SCV)分别为(40.5±3.2)m.s-1和(34.3±3.1)m.s-1,感觉神经动作电位波幅分别为(9.0±3.8)μV和(7.2±3.3)μV,2组比较差异有显著性(P<0.05)。结论:参麦注射液对含奥沙利铂化疗方案所致的神经毒性具有明显的防治作用。     

Oxaliplatin. A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies

Oxaliplatin is a platinum compound that inhibits DNA synthesis, primarily by causing intrastrand cross-links in DNA. Oxaliplatin has a broad spectrum of antineoplastic activity and has demonstrated a lack of cross-resistance with other platinum compounds. In patients with metastatic colorectal cancer, intravenous oxaliplatin has been trialled as a monotherapy and in combination with other agents. The highest response rates were achieved when oxaliplatin was used in combination with fluorouracil/folinic acid (leucovorin; calcium folinate), typically > or = 50% in the first-line setting and 13 to 45% as a second-line therapy. First-line triple therapy with oxaliplatin and fuorouracil/folinic acid achieved significantly higher response rates and longer median progression-free survival than fluorouracil/folinic acid therapy alone. However, no significant difference in the median duration of overall survival was found. This may be a consequence of the subsequent use of oxaliplatin and/or surgery after disease progression in patients who relapsed after fluorouracil/folinic acid therapy alone. Neoadjuvant therapy with oxaliplatin/fluorouracil/folinic acid has proven beneficial in enabling surgical removal of previously unresectable liver metastases. In 2 studies, surgery with curative intent was performed in 16 and 51% of patients with initially unresectable liver metastases following oxaliplatin/fluorouracil/folinic acid therapy; the 5-year survival rates were 40 and 50%, respectively. In patients with advanced ovarian cancer, first-line therapy with oxaliplatin/cyclophosphamide achieved an objective response rate which did not differ significantly from that of cisplatin/cyclophosphamide (33 vs 42%). In addition, oxaliplatin has shown efficacy in patients with platinum-pretreated ovarian cancer and achieved objective response rates similar to paclitaxel in this setting (16 vs 17%). Promising results have also been found with oxaliplatin in patients with non-Hodgkin's lymphoma, breast cancer, mesothelioma and non-small cell lung cancer. Reversible, cumulative, peripheral sensory neuropathy is the principle dose-limiting factor of oxaliplatin therapy. Haematological and gastrointestinal toxicities occur frequently but are generally mild to moderate in intensity. CONCLUSION: Oxaliplatin in combination with fluorouracil/folinic acid is an effective treatment option for patients with metastatic colorectal cancer, both as a first-line therapy and in patients refractory to previous chemotherapy. Although preliminary results failed to show any overall survival advantage of this regimen over fluorouracil/folinic acid alone, this may be a consequence of trial design and requires further examination. Additional clinical investigation of oxaliplatin in patients with other cancers is warranted given the promising results achieved in early trials, most notably in patients with platinum-pretreated ovarian cancer.     

Oxaliplatin-induced hepatocellular injury and ototoxicity: a review of the literature and report of unusual side effects of a commonly used chemotherapeutic agent

After extensive literature review utilizing PubMed and Medline searches, we present a rare case of oxaliplatin-induced grade 3/4 hepatocellular injury and ototoxicity. The patient is a 46-year-old female diagnosed with stage IIIC (pT3N2bM0) adenocarcinoma of the sigmoid colon. PET/CT prior to surgery and chemotherapy was negative for distant metastatic disease and baseline liver-associated enzymes were within normal limits. Following sigmoidectomy, patient began adjuvant chemotherapy with 5-florouracil, leucovorin, and oxaliplatin (mFOLFOX-6). Cycle 1 was complicated only by refractory nausea. However, cycle 2 was complicated by vertigo with refractory nausea, tinnitus, and marked elevation in liver enzymes in a hepatocellular pattern. Extensive workup was negative and the etiology of her symptoms and grade 3/4 hepatocellular injury was hypothesized to be the result of oxaliplatin. Aspartate aminotransferase and alanine aminotransferase decreased after two additional weeks off therapy and during cycle 3 in which oxaliplatin was held. She had no evidence of 5-florouracil toxicity. On cycle 4, oxaliplatin was restarted at 50% dose; symptoms and liver-associated enzymes remained stable. However, oxaliplatin was increased up to 75% full dose for cycle 5 with reported vertigo, tinnitus, nausea, and return of elevation in liver-associated enzymes. Oxaliplatin is a chemotherapy agent widely used in the treatment of many malignancies including colon cancer. Side effects include peripheral neuropathy, gastrointestinal toxicity, neutropenia, grade 1/2 hepatocellular injury, and hepatic vascular lesions. However, grade 3/4 hepatocellular injury and ototoxicity are extremely rare with the administration of oxaliplatin. Therefore, we present the unusual chemotherapy side effects.     

Oxaliplatin: a review of its use in the management of metastatic colorectal cancer.

Oxaliplatin is a cytotoxic agent which, like other platinum compounds, acts primarily by causing inter- and intra-strand cross-links in DNA, thereby inhibiting DNA synthesis. Oxaliplatin has a bulky carrier ligand which is thought to enhance cytotoxicity and abolish cross-resistance between oxaliplatin and other platinum compounds. Phase II and III clinical trials have found oxaliplatin combined with fluorouracil/calcium folinate (leucovorin/folinic acid) to be an effective first- and second-line treatment for patients with metastatic colorectal cancer. First-line triple therapy with oxaliplatin and fluorouracil/calcium folinate achieved significantly higher response rates than fluorouracil/calcium folinate alone in 2 phase III studies (objective response rates 59 vs 23% and 50.7 vs 22.3%). In addition, median progression-free survival was longer with triple therapy in both studies (8.9 vs 5.2 and 8.75 vs 6.0 months). However, there was no significant difference in median duration of survival between treatment groups, although this may be a consequence of the subsequent use of oxaliplatin and/or surgery in patients who relapsed during therapy with fluorouracil/calcium folinate alone. About 30 to 45% of patients (whose disease progressed during or after fluorouracil-based therapy) responded to second-line combination therapy with oxaliplatin and fluorouracil/calcium folinate. Median progression-free survival ranged from 7 to 10 months and the median duration of survival from 10 to 17 months. Objective responses were achieved in 20 and 24% of patients in 2 small trials of first-line oxaliplatin monotherapy and in about 10% of patients given the drug as a second-line option. Peripheral sensory neuropathy is the dose-limiting toxicity associated with oxaliplatin. Severe neurotoxicity has been estimated to occur in 10% of patients after 6 treatment cycles and in 50% after 9 cycles of an oxaliplatin dosage of 130 mg/m2 once every 3 weeks. It is cumulative, but reversible on discontinuation of therapy. Nausea, vomiting and diarrhoea are common, but are usually mild to moderate. Myelosuppression is also observed, but is usually mild. Conclusion: oxaliplatin is a promising treatment option for patients with metastatic colorectal cancer. It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with fluorouracil/calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over fluorouracil/calcium folinate alone. Promising results have been found in studies of the drug as monotherapy, and oxaliplatin may also prove useful in the neoadjuvant setting in patients with unresectable liver metastases; however, data are limited at present.     

Guillain-Barré syndrome in a patient with metastatic colon cancer receiving oxaliplatin-based chemotherapy

We report Guillain-Barre syndrome (GBS), developed in a patient with metastatic colon cancer, receiving oxaliplatin-based chemotherapy. The 53-year-old patient was treated with first-line chemotherapy consisting of oxaliplatin 45 mg/m2, 5-fluorouracil 450 mg/m2 and folinic acid 200 mg/m2, all given on the same day in a weekly schedule. After 13 weeks of treatment and a cumulative oxaliplatin dose of 585 mg/m2, the patient developed unsteadiness of gait, dysphagia, and weakness of both the upper and lower limbs, as well as impairment of all sensory modalities. Clinical examination, computed tomography and magnetic resonance imaging scans of the brain, blood tests, nerve conduction studies, and cerebrospinal fluid analysis confirmed the diagnosis of GBS. Intravenous immunoglobulin G was administered for 5 days and the patient recovered fully. Oxaliplatin can cause acute and delayed neurotoxicity, but this is the first report of GBS in a patient receiving oxaliplatin-based chemotherapy. Elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, induced by oxaliplatin, may represent the relevant causal links involved in the cascade of events which have led to the immune-mediated demyelination in the peripheral nervous system in this patient.     

左卡尼汀对预防奥沙利铂周围神经毒性作用的临床观察

目的观察左卡尼汀对奥沙利铂引起的周围神经毒性反应的预防性治疗作用。方法 70例接受奥沙利铂化疗的肿瘤患者随机分为两组,预防性治疗组患者在应用奥沙利铂化疗同时给予左卡尼汀治疗,对照组化疗方案与前组相同但未接受左卡尼汀预防性治疗。分别比较两组患者的神经毒性总发生率、外周感觉神经毒性级别、出现外周神经毒性时间及肿瘤相关性疲劳分级和体力状况评分。结果预防性治疗组神经毒性发生率、外周感觉神经毒性级别均低于对照组,且差异有统计学意义(P<0.05)。结论应用奥沙利铂联合化疗中预防性给予左卡尼汀,可减少化疗相关的神经毒性,值得进一步研究。     

钙镁合剂联合护理干预缓解草酸铂所致神经毒性的观察

目的探讨护理干预联合应用钙镁合剂对减轻草酸铂神经毒性反应的效果。方法进行草酸铂化疗的60例患者第1周期化疗采取常规护理方法,第2周期化疗采用护理干预联合应用钙镁合剂的方法,比较神经毒性反应发生情况与程度。结果使用常规方法发生神经毒性60例,2级以上的有30例;采用护理干预方法后发生神经毒性反应60例,2级以上的有10例。干预后神经毒性反应减轻,有显著性差异(χ2=17.692,P<0.01)。结论护理干预联合应用钙镁合剂可以降低草酸铂神经毒性反应的发生率,能减轻神经毒性反应的程度。     

早期系统化健康教育对预防奥沙利铂神经毒性、提高患者满意度的效果观察

目的探讨早期系统化健康教育对预防奥沙利铂(L.OHP)引起的神经毒性及提高患者满意度的效果观察。方法将四川省人民医院2010年4月至2011年4月56例接受奥沙利铂治疗的癌症患者,其中男30例,女26例,年龄40～68岁,直肠癌42例、胃癌14例随机分为两组:实验组28例(A组);对照组28例(B组)。干预组在化疗前进行系统化的健康指导,并将健康指导贯穿于患者住院整过程,对照组按常规在化疗时进行健康指导,并将健康指导贯穿于住院过程。观察两组患者神经毒性发生情况及患者住院期间满意度。结果 A、B两组神经毒性的发生率分别为7%和16%,干预组患者满意度远远高于对照组。干预组的疗效优于常规处理对照组(P<0.01)。结论化疗前进行系统化护理干预能有效预防奥沙利铂所致神经毒性、提高住院患者满意度。     

奥沙利铂化疗致外周神经毒性的护理体会

奥沙利铂是一种新的铂类抗癌药,具有广谱的体外细胞毒性及体内抗肿瘤活性作用,对顺铂耐药的肿瘤模型仍然有效,常用于转移性结、直肠癌或辅助治疗原发性肿瘤完全切除后三期结肠癌,也适用于经5-氟尿嘧啶治疗失败的结、直肠癌转移患者。但其突出的不良反应是外周感觉神经毒性,主要表现为感觉迟钝和(或)感觉异常,遇冷加重,这种毒性作用与其剂量有关,可表现为急性神经毒性和迟发型感觉神经障碍,影响其疗效和患者的生活质量。研究表明,治疗前后给予肿瘤患者正确有效的护理措施对于提高化疗的疗效和改善患者的预后具有十分重要的临床意义。因此,本文对健康指导、预防、对症护理及心理护理四个方面的护理体会进行了归纳,以期为奥沙利铂毒副反应的有效护理提供更多的参考依据。     

Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review

Peripheral neurotoxicity is a major complication associated with the use of chemotherapeutic agents such as platinum compounds, taxanes and vinca alkaloids. The neurotoxicity of chemotherapy depends not only on the anticancer agent(s) used, the cumulative dose and the delivery method, but also on the capacity of the nerve to cope with the nerve-damaging process. The sensory and motor symptoms and signs of neurotoxicity are disabling, and have a significant impact on the quality of life of cancer patients. Moreover, the risk of cumulative toxicity may limit the use of highly effective chemotherapeutic agents. Therefore, prophylaxis and treatment of peripheral neurotoxicity secondary to chemotherapy are major clinical issues. Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, plays an essential role in intermediary metabolism. Some of the properties exhibited by ALC include neuroprotective and neurotrophic actions, antioxidant activity, positive actions on mitochondrial metabolism, and stabilisation of intracellular membranes. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various aetiologies, including chemotherapy-induced peripheral neuropathy (CIPN). In several experimental settings, the prophylactic administration of ALC prevented the occurrence of peripheral neurotoxicity commonly induced by chemotherapeutic agents. In animal models of CIPN, ALC administration promoted the recovery of nerve conduction velocity, restored the mechanical nociceptive threshold, and induced analgesia by up-regulating the expression of type-2 metabotropic glutamate receptors in dorsal root ganglia. These results, plus the favourable safety profile of ALC in neuropathies of other aetiologies, have led to the effects of ALC on CIPN being investigated in cancer patients. Preliminary results have confirmed the reasonably good tolerability profile and the efficacy of ALC on CIPN. The present studies support the use of ALC in cancer patients with persisting neurotoxicity induced by paclitaxel or cisplatin treatment.