Antoinetta J. M. Beijers

Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide and newer agents such as bortezomib. The incidence and degree of neuropathy depends on the type of cytotoxic drug, the duration of administration, cumulative dose and pre-existing peripheral neuropathy. Because of increasing survival rates of patients treated with neurotoxic agents, CIPN is accompanied by a significant decrease in the patient's quality of life among cancer survivors. Therefore, several neuroprotective strategies, including calcium/magnesium infusion, amifostine, gluthatione, glutamine, acetyl-L-carnitine and erythropoietin as most promising, have been investigated to decrease the neurotoxicity without compromising anti-tumour efficacy. However, clinical evidence for the efficacy of these drugs is sparse. In this review we will give an outline of the neurotoxic effects of chemotherapeutic agents, their clinical manifestations and potential neuroprotective strategies.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of cytostatics. With improved survival among cancer patients, CIPN may have a major impact on quality of life (QoL) of cancer survivors. OBJECTIVE: To determine the occurrence of CIPN induced by oxaliplatin and taxanes and its impact on QoL median 6 months after chemotherapy. METHODS: All patients who received their last treatment with oxaliplatin or taxanes in 2 consecutive years in the Máxima Medical Centre, the Netherlands, were eligible for the study. Neurotoxicity and its effect on QoL was assessed with the recently developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) median 6 months after cessation of therapy. RESULTS: Of the 58 eligible patients, 43 (74.1%) completed the questionnaire. After a median follow-up of 6.5 months after cessation of therapy, most of the patients experienced neurotoxicity in the upper and lower extremities (78.8% and 89.7%, respectively). Overall, the most-reported complaints included numbness and tingling in hands as well as feet, suffering from cold feet, and trouble distinguishing objects in the hands. Housekeeping difficulties were reported in 12.8% of patients, and 20.5% of patients became more dependent on others because of the neurotoxicity. Overall, QoL was negatively affected by the impact of CIPN in 48.6% of patients. LIMITATIONS: Due to the small sample size selection bias cannot be ruled out and no data about CIPN during treatment were available. Conclusions After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL. CONCLUSIONS: After a median follow-up of 6.5 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL. More research is needed to assess the impact of neurotoxicity on QoL.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of oxaliplatin which can negatively influence quality of life. We aimed to study the influence of cumulative dose, dose schedule and dose reductions of adjuvant oxaliplatin on long-term severity and prevalence of CIPN among colorectal cancer (CRC) survivors. MATERIAL AND METHODS: In total 207 patients, diagnosed with CRC between 2000 and 2009 who underwent adjuvant treatment with oxaliplatin, were included. They completed the EORTC QLQ-CIPN20 2-11 years after diagnosis. Data on oxaliplatin administration and acute neuropathy during treatment were extracted from the medical files. Subscales were analyzed with analysis of covariance and neuropathy symptoms with logistic regression analysis. RESULTS: Patients who received cumulative oxaliplatin dose of ≥ 842 mg/m(2) had a significantly worse EORTC QLQ-CIPN20 sensory score compared to those who received a low cumulative dose of < 421 mg/m(2) (mean 19 vs. 8; p = 0.02). They more often reported tingling toes/feet (13% vs. 2%, respectively; p = 0.01). Dose intensity and time delay did not influence the occurrence of CIPN. Patients receiving a dose reduction because of neuropathy (N = 50) reported a significantly worse sensory score at very similar cumulative doses, than those who did not receive a dose reduction because of neuropathy (N = 96) (mean 21 vs. 15; p = 0.01). CONCLUSION: Cumulative dose of oxaliplatin is associated with long-term CIPN. The risk of developing long-term CIPN could only be reduced by decreasing the cumulative dose, whereas delay probably is not beneficial. Patients receiving a dose reduction because of acute neuropathy are still at risk of developing long-term CIPN. Future studies should focus on identifying patients who are at risk of developing CIPN.