Clinical aspects and molecular basis of oxaliplatin neurotoxicity: Current management and development of preventive measures

Gamelin, Érick; Gamelin, Laurence; Bossi, Laura; Quasthoff, Stefan

doi:10.1053/sonc.2002.35525

Cited by 279 publications

(199 citation statements)

References 46 publications

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“…However, this oxaliplatin-related side effect was reported to be completely reversible after omission of oxaliplatin in more than 80% of the patients within 8 months (Gamelin et al, 2002).…”

Section: Discussionmentioning

confidence: 96%

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

et al. 2008

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This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m À2 , day 1) plus capecitabine (1000 mg m À2 b.i.d., days 1 -14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0 -15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3 -11.7; ECC: 16.8 months; 95% CI, 12.7 -20.5), and 5.2 months (95% CI, 0.6 -9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3 -4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.

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Section: Discussionmentioning

confidence: 96%

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

et al. 2008

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“…Acute neurotoxicity (paresthesias or dysesthesias), although frequently seen, is generally transient and mild (Gamelin et al, 2002). However, after several cycles of oxaliplatin therapy, a late-onset cumulative sensory neuropathy may occur.…”

Section: Oxaliplatin In the First-line Treatment Of Advanced Crcmentioning

confidence: 99%

Management of advanced colorectal cancer: state of the art

Saunders

Iveson

2006

Br J Cancer

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Colorectal cancer (CRC) caused over 500 000 deaths worldwide in 2002. Recent advances in the treatment of advanced disease include the incorporation of two new cytotoxic agents, irinotecan and oxaliplatin, into first-line regimens. The concept of planned sequential therapy involving three active agents during the course of a patient's treatment is evolving. Coupled with the integrated use of targeted monoclonal antibodies, we can now expect overall survival rates for advanced disease to exceed 20 months. This review considers current treatments and suggests where future progress may occur.

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“…A tangled panel of symptoms may be disabling for treated patients, adversely affecting activities of daily living and thereby quality of life, until suspension of the therapy. 12,17,42 Whereas neuropathy acutely developed is usually self-limiting, often resolving the symptoms within days, repeated oxaliplatin administration induces a chronic neuropathy that cannot be resolved between cycles. 3,9,14,17 Randomized trials demonstrating a prophylactic or therapeutic effect of antihyperalgesic drugs on oxaliplatin's cumulative neurotoxicity are still lacking or inconclusive.…”

mentioning

confidence: 99%

“…12,17,42 Whereas neuropathy acutely developed is usually self-limiting, often resolving the symptoms within days, repeated oxaliplatin administration induces a chronic neuropathy that cannot be resolved between cycles. 3,9,14,17 Randomized trials demonstrating a prophylactic or therapeutic effect of antihyperalgesic drugs on oxaliplatin's cumulative neurotoxicity are still lacking or inconclusive. 2,24 Among pharmacological treatments, antioxidant compounds have been tested as possible therapeutic approaches.…”

mentioning

confidence: 99%

Oxaliplatin-Induced Neuropathy: Oxidative Stress as Pathological Mechanism. Protective Effect of Silibinin

Mannelli

Zanardelli

Failli

et al. 2012

The Journal of Pain

161

120

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Oxaliplatin is the standard treatment for advanced colorectal cancer. Its dose-limiting toxicity is the development of a painful neuropathic syndrome sustained by unclear mechanisms. Although the oxidative hypothesis is a matter of debate, direct data about oxidative damage induced in vivo by anticancer agents are lacking and the efficacy of the available antioxidant compounds are unsatisfactory. In a rat model of painful oxaliplatin-induced neuropathy (2.4 mgkg À1 i.p., daily for 21 days), we described an important component of oxidative stress. In the plasma of oxaliplatin-treated rats, the increases in carbonylated protein and thiobarbituric acid reactive substances were the index of the resultant protein oxidation and lipoperoxidation, respectively. The same pattern of oxidation was revealed also in the sciatic nerve, and in the spinal cord where the damage reached the DNA level. The antioxidant compound silibinin (100 mgkg À1 per os), administered once a day, starting from the first day of oxaliplatin injection until the 20th, prevented oxidative damage as did a-tocopherol. Repetitive administration of silibinin, as well as a-tocopherol, reduced oxaliplatin-dependent pain induced by mechanical and thermal stimuli. Antioxidants were also able to improve motor coordination. The antineuropathic effect of both molecules improved by about 50% oxaliplatin-induced behavioral alterations.Perspective: This study characterizes oxidative stress parameters in a rat model of oxaliplatininduced neuropathy. A relationship between the improvement of oxidative alterations and pain relief is established in rats treated with natural antioxidant compounds like a-tocopherol and silibinin. Silibinin could be a valid therapeutic option for chemotherapy-induced neuropathy.

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Clinical aspects and molecular basis of oxaliplatin neurotoxicity: Current management and development of preventive measures

Cited by 279 publications

References 46 publications

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

Management of advanced colorectal cancer: state of the art

Oxaliplatin-Induced Neuropathy: Oxidative Stress as Pathological Mechanism. Protective Effect of Silibinin

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