Neuropathy oxaliplatin-induced

Patients should be closely monitored for side effects that require aggressive intervention such as irinotecan-induced diarrhea and bevacizumab-induced GI perforation. Patients should be evaluated for other treatment-specific side effects such as oxaliplatin-induced neuropathy, cetuximab and panitumumab-induced skin rash, and bevacizumab-induced hypertension and proteinuria. 

In a pilot study in 15 patients, subcutaneous amifostine was given 20 minutes before oxaUplatin, in order to counteract oxaliplatin-induced peripheral neurosensory toxicity. In 10 patients, this regimen reduced the severity of cumulative neuropathy without compromising antitumor efficacy the amifostine was well tolerated (114). 

Carbamazepine is a potent sodium channel blocker and has therefore been studied in the prevention of oxaliplatin-induced neuropathy (116). The doses of carbamazepine were adjusted to produce serum concentrations in the range 30-60 pg/ml. None of the patients who took carbamazepine reported symptoms of peripheral neurotoxicity however, two patients (one who forgot to take carbamazepine and one who stopped taking it because he felt tired) developed grade-1 peripheral sensory neurotoxicity. These symptoms were abolished when carbamazepine was restarted. One can therefore speculate that the concomitant use of carbamazepine may allow the use of a higher cumulative dose of oxaliplatin without the occurrence of grade-4 neuropathy. However, a multicenter trial is warranted to confirm these encouraging preliminary results (117). 

Eckel F, Schmelz R, Adelsberger H, Erdmann J, Quasthoff S, Lersch C. Prophylaxe der OxaUplatin-indu-zierten Neuropathie mit Carbamazepin. Erne PUotstudie. [Prevention of oxaliplatin-induced neuropathy by carbamazepine. A pilot study.] Dtsch Med Wochenschr 2002 127(3) 78-82. 

Inada M, Sato M, Morita S et al (2010) Associations between oxaliplatin-induced peripheral neuropathy and polymorphisms of the ERCC1 and GSTP1 genes. Int J Clin Pharmacol Ther 48 729-734... 

Kanai M, Yoshioka A, Tanaka S et al (2010) Associations between glutathione S-transferase % Ilel05Val and glyoxylate aminotransferase ProllLeu and Ile340Met polymorphisms and early-onset oxaliplatin-induced neuropathy. Cancer Epidemiol 34 189-193... 

Won HH, Lee J, Park JO et al (2012) Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients. Cancer 118 2828-2836... 

Antonacopoulou AG, Argyriou AA, Scopa CD et al (2010) Integrin beta-3 L33P a new insight into the pathogenesis of chronic oxaliplatin-induced peripheral neuropathy Eur J Neurol 17 963-968... 

Oxaliplatin is a third generation diaminocyclohexane platinum analog. Its mechanism of action is identical to that of cisplatin and carboplatin. However, it is not cross-resistant to cancer cells that are resistant to cisplatin or carboplatin on the basis of mismatch repair defects. This agent was recently approved for use as second-line therapy in metastatic colorectal cancer following treatment with the combination of fluorouracil-leucovorin and irinotecan, and it is now widely used as first-line therapy of this disease as well. Neurotoxicity is dose-limiting and characterized by a peripheral sensory neuropathy, often triggered or worsened upon exposure to cold. While this neurotoxicity is cumulative, it tends to be reversible—in contrast to cisplatin-induced neurotoxicity. 

The further development of the third-generation platinum derivative tetraplatin (ormaplatin, trans-u, L-l,2-diaminocyclohexane tetrachloroplatinnm) has been abandoned, because drug-induced severe motor and sensory peripheral neuropathy occurred even at low cumulative doses. The high neurotoxic potential of tetraplatin may be associated with its pharmacokinetics it is rapidly metabolized to 1,2-DACH-platinnm dichloride, which was 3.8 times more nenro-toxic than oxaliplatin in a neurite ontgrowth assay (45). 

---