![]() 18 Although most of the presented results were obtained in cisplatin models, it is likely that the pathophysiology of chronic CIPN induced by carboplatin and oxaliplatin is similar. The dorsal root ganglia (DRG) are the main target of platinum drug–induced CIPN. An example is brentuximab vedotin (Adcetris) which can be associated with mild, mostly non–clinically relevant sensory neuropathy. The use of biological agents has also been occasionally associated with CIPN. Several risk factors include pre-existing neuropathy, age, and comorbidities. 15 Bortezomib-induced CIPN occurs in about half of the patients receiving treatment with this drug, 16 and the cumulative dose of bortezomib has been associated with an increased severity. Sometimes bortezomib is used in combination chemotherapy with thalidomide, with a possible cumulative effect of CIPN. Bortezomib, a proteasome inhibitor, is used in multiple myeloma treatment. 14 The thalidomide analogs lenalidomide and pomalidomide are less neurotoxic. The thalidomide dose and incidence of CIPN have been reported, with studies evidencing a cumulative dose relationship. In these studies, the incidence of clinically relevant sensory neuropathy was variable, from 6% to 71%. The number of subjects treated with epothilones is relatively small, and most of them were exposed to ixabepilone. The use of an albumin-bound paclitaxel formulation (abraxane) seems to be less neurotoxic. 11 The risk of developing severe taxane-induced CIPN is related to treatment interval. 10 The neurotoxic threshold is around 1000 mg/m 2 for paclitaxel and 400 mg/m 2 for docetaxel. Among taxanes, paclitaxel is slightly more neurotoxic than is docetaxel. Taxanes and epothilones act on the cytoskeleton by enhancing tubulin polymeration. 9 Vinblastine, vinflunine, and vinorelbine are less neurotoxic. Sensory signs are the earliest with doses >6–8 mg/m, 2 distal motor weakness is not uncommon, 7 as well as neuropathic pain 8 and autonomic dysfunction. The severity of vincristine-induced CIPN is dose-related, ensuing in most patients after the administration of 4 mg/m 2 of the drug. The toxicity profile of the different antitubulins is different in clinical presentation, incidence, severity, and outcome. 5 Predictors for severe chronic oxaliplatin-induced CIPN have been suggested. CIPN is frequently persistent and dose-dependent, with a threshold dose of 500–600 mg/m 2. Acute, transient, cold-related paresthesias jaw spasms and cramps occur in virtually all the patients but are reversible. Oxaliplatin presents 2 different clinical features. The presence of other known risk factors for CIPN (e.g., alcohol consumption, diabetes, high serum creatinine levels, or age) has not been demonstrated to remarkably influence the incidence and severity of cisplatin-induced CIPN. 3 Cisplatin liposomal formulation (lipoplatin) and carboplatin seem to be less neurotoxic. Literature data suggest that a threshold for the earliest signs of cisplatin-induced CIPN is 250–350 mg/m 2, 2 with increasing incidence and severity with higher doses. Platinum drugs are frequently associated with CIPN. 1 Several confounding factors and also improper assessment play a role, and data obtained from oncology clinical trials must be carefully evaluated. The epidemiology of anticancer drug–induced peripheral neurotoxicity (CIPN) is still unclear. As the number of long-term cancer survivors increases and a new focus on long-term effects of chemotherapy-induced neuropathies emerge, concepts of rehabilitation need to be implemented to improve the patients’ functions and quality of life. The role of synergistic neurotoxicity caused by previously given chemotherapies and concomitant chemotherapies and the role pre-existent neuropathy on the development of a CIPN is not clear. The most frequent substances causing CIPN are platin compounds, vinka alkaloids, taxanes, and bortezomib and thalidomide. Usually, the appearance of CIPN is dose dependent, although in at least 2 drugs (oxaliplatin and taxanes), immediate toxic effects occur. CIPN are predominately sensory, length-dependent neuropathies that develop after a typical cumulative dose. Several drug-dependent pathogenetic mechanisms exist. ![]() Neurotoxic drugs are becoming a major dose-limiting factor. Contrary to hematologic adverse effects, which can be treated with hematopoetic growth factors, neither prophylaxis nor specific treatment is available, and only symptomatic treatment can be offered. Peripheral neuropathies induced by chemotherapy (CIPN) are an increasingly frequent problem.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |