ABSTRACT
The peripheral nervous system, in general, is vulnerable to chemotherapeutic agent toxicity, and chemotherapy-induced peripheral neuropathy (CIPN) underlies chemotherapy-induced neuropathic pain (CINP) during or following treatment with certain cancer chemotherapeutic drugs. The pain can persist long after cessation of drug administration, and is dif•cult to treat using currently available approaches. CIPN is characterized by distally predominant neuropathy, with lower limbs
5.1 Introduction .................................................................................................. 113 5.2 Peripheral Nervous System Vulnerability .................................................... 115 5.3 Chemotherapeutic Drugs: Classes and Agents ............................................. 116
5.3.1 Platinum-Based Chemotherapeutic Agents ...................................... 116 5.3.1.1 Cisplatin ............................................................................. 116 5.3.1.2 Carboplatin ........................................................................ 120 5.3.1.3 Oxaliplatin ......................................................................... 120
5.3.2 Taxanes ............................................................................................. 122 5.3.2.1 Paclitaxel ............................................................................124 5.3.2.2 Docetaxel ........................................................................... 125
5.3.3 Vinca Alkaloids ................................................................................ 125 5.3.4 Suramin ............................................................................................ 126 5.3.5 Thalidomide ...................................................................................... 126
5.4 Some Major Unanswered Questions ............................................................. 127 5.5 Conclusion .................................................................................................... 128 Declarations and Acknowledgment ....................................................................... 128 References .............................................................................................................. 128
typically evidencing signs and symptoms before upper limbs. This chapter reviews CIPN; peripheral neuropathy associated with chemotherapeutic agents is well documented and there are putative mechanisms. Platinum-based drugs, taxanes, vinca alkaloids, suramin, and thalidomide, in particular, are associated with relatively high rates of CIPN. Platinum drugs are also known for coasting, a phenomenon in which symptoms persist or even worsen after the drug is discontinued. Taxanes are associated with rapid-onset cold-induced neuropathy, and thalidomide-induced CIPN is often irreversible. Different patterns of symptoms presumably re®ect different mechanisms of toxicity, which include formation of DNA adducts, disruption of axonal transport, interference with ion channel function, and induction of apoptosis, among others. Greater understanding of the mechanisms involved in CIPN could better inform clinical practice regarding the optimal use of existing cancer chemotherapeutic drugs, individually or in combinations; stimulate the development of new antineoplastic agents with superior adverse effect pro•les; and provide more optimal pain management in chemotherapy patients.
