Chemotherapy-induced peripheral neuropathy is a progressive, enduring, and often irreversible condition featuring pain, numbness, tingling and sensitivity to cold in the hands and feet that afflicts between 30% and 40% of patients undergoing chemotherapy.
Symptoms
Though the symptoms are mainly sensory – pain, tingling, numbness and temperature sensitivity – in some cases motor nerves are affected, and occasionally, also, the autonomic nervous system. CIPN often follows the first chemotherapy dose and increases in severity as treatment continues, but this progression usually levels off at completion of treatment. The platinum-based drugs are the exception; with these drugs, sensation may continue to deteriorate for several months after the end of treatment. Some CIPN appears to be irreversible. CIPN disrupts leisure, work, and family relations, and the pain of CIPN is often accompanied by sleep and mood disturbance, fatigue and functional difficulties. A 2007 American Cancer Society study found that most patients did not recall being told to expect CIPN, and doctors monitoring the condition rarely asked how it affects daily living but focused on practical effects such as dexterity and gait.
Causes
Chemotherapy drugs associated with CIPN include thalidomide, the epothilones such as ixabepilone, the vinca alkaloidsvincristine and vinblastine, the taxanes paclitaxel and docetaxel, the proteasome inhibitors such as bortezomib, and the platinum-based drugs cisplatin, oxaliplatin and carboplatin. Whether CIPN arises, and to what degree, is determined by the choice of drug, duration of use, the total amount received and whether the patient already has peripheral neuropathy. It is not known what causes the condition, but microtubule and mitochondrial damage, and leaky blood vessels near nerve cells are some of the possibilities being explored. One of the more promising theories is that chemotherapeutic drugs act by disrupting microtubules of the mitotic spindle during cell division, causing the disruption of microtubule based axonal transport of neurons. Also, the nervous system has programmed cell death pathways that are particularly sensitive to DNA damage induced by many chemotherapeutic agents. Pain can often be helped with drug or other treatment but the numbness is usually resistant to treatment.
was studied in two large double-blindplacebo-controlled trials and seemed to reduce neurotoxicity without interfering with the therapeutic effect, but shortcomings in the trial designs make confident interpretation of the results impossible. As of September 2013, patients are being recruited for a more definitive study.
Intravenous calcium and magnesium
In a study of patients receiving oxaliplatin treatment, only 4 percent of those also receiving intravenous calcium and magnesium before and after each oxaliplatin dose had to discontinue treatment due to neurotoxicity, compared to 33 percent who were receiving intravenous placebo; onset of neuropathy was also significantly delayed in the ca/mg patients, and only 22 percent of the ca/mg patients had long-term CIPN of grade 2 or worse compared with 41 percent of those on placebo. Overall, trials of ca/mg infusion suggest there are no serious harmful side effects and it may be an effective preventative therapy — the number of patients so far studied is small, however, and confident conclusions cannot be drawn.
