Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin

Petrioli, Roberto; Pascucci, Alessandra; Francini, Edoardo; Marsili, Stefania; Sciandivasci, Angela; Tassi, Rossana; Civitelli, Serenella; Tanzini, G.; Lorenzi, Marco; Francini, Guido

doi:10.1007/s00280-007-0454-3

Cited by 50 publications

(41 citation statements)

References 24 publications

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“…A further 3 cases have been reported with cumulative doses of 680–860 mg/m 2 [15], and a final case in a patient after receiving cisplatin and oxaliplatin therapy [14]. The 5 patients in the present series received cumulative oxaliplatin doses in the range of 574–1,100 mg/m 2 , within the typical dose range which induces severe neurotoxicity in 10–25% of patients [7,11,12,13,27]. …”

Section: Discussionmentioning

confidence: 96%

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Oxaliplatin-Induced Lhermitte’s Phenomenon as a Manifestation of Severe Generalized Neurotoxicity

Park

Lin²,

Krishnan³

et al. 2009

Oncology

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Objectives: Lhermitte’s phenomenon, characterized by ‘electric-shock’ sensations precipitated by neck flexion, may develop during oxaliplatin treatment. Limited cases have been described previously and the pathophysiology underlying Lhermitte’s phenomenon in oxaliplatin-treated patients has not been established. Methods: Patients who developed Lhermitte’s phenomenon during oxaliplatin therapy were investigated by neurological examination, neurotoxicity grading and conventional nerve conduction studies (NCS). Structural (magnetic resonance imaging) and functional (somatosensory evoked potentials) spinal assessment was also undertaken. Sensory nerve excitability recordings were performed longitudinally across treatment to investigate ion channel function. Results: Five oxaliplatin-treated patients reported Lhermitte’s phenomenon, with a mean cumulative dose of 861 ± 84 mg/m² oxaliplatin (range 574–1,100 mg/m²). NCS revealed severe sensory neuropathy in all patients. There was no evidence of structural or functional spinal cord damage. Nerve excitability studies revealed progressive alterations in sensory excitability throughout treatment, consistent with oxaliplatin-induced nerve dysfunction. In patients with Lhermitte’s phenomenon, refractoriness was reduced to –14.4% (confidence interval, CI: –20.5 to –8.4%) by late treatment, a significantly greater reduction than in oxaliplatin-treated patients who did not develop Lhermitte’s phenomenon (–2.7%; CI: –7.6 to 2.2; p = 0.013). Conclusions: Lhermitte’s phenomenon represents a severe presentation of oxaliplatin-induced neurotoxicity, associated with generalized nerve dysfunction in the absence of structural spinal abnormalities.

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Section: Discussionmentioning

confidence: 96%

“…Neurotoxicity represents the major dose-limiting toxicity with severe symptoms occurring in up to 20% of patients at a cumulative dose of 750–850 mg/m 2 [7,11,12]. While Lhermitte’s phenomenon was reported in the early treatment trials [7,9,13], only a handful of case reports have been described in the literature to date [14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Oxaliplatin-Induced Lhermitte’s Phenomenon as a Manifestation of Severe Generalized Neurotoxicity

Park

Lin²,

Krishnan³

et al. 2009

Oncology

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“…In their neurotoxicity study, Petroli et al included patients who had terminated therapy from 1 to 12 months previously. After a month, manifestations of neurotoxicity had a severity grade ≥ 2 in 25% of the patients, while after 12 months only 3% of the patients still had symptoms with severity grade 2 [15]. In a study by Tournigand et al the incidence of neuropathy reached 88%; however, the patients were treated with the FOLFOX-6 regimen, in which the dose of oxaliplatin was increased to 100 mg/m 2 p.c.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Toxicity of Anticancer Chemotherapy in Patients with Colon Cancer

et al. 2015

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Background. Modern anticancer chemotherapy can cause numerous adverse effects in the organism, whose functioning has already been disrupted by the neoplastic process itself. Objectives. The aim of the study was to evaluate and compare the frequency and severity of the toxicity of FOLFOX-4 and CLF-1 anticancer therapy in patients with colon cancer, and to analyze certain factors that might have increased the toxicity of the chemotherapy. Material and Methods. The study involved 64 patients suffering from generalized colon cancer, including 48 patients treated according to the FOLFOX-4 regimen and 16 patients treated according to the CLF-1 regimen. The toxicity of each regimen was analyzed on the basis of a confidential questionnaire formulated by the authors and laboratory research according to the extended WHO toxicity criteria. Results. The analysis of the symptoms of toxicity symptoms associated with the use of the FOLFOX-4 and CLF-1 therapeutic regimens revealed that the most common side effects included nausea and vomiting, despite ondansetron premedication, and neurotoxicity. Disruption of the functioning of the nervous system under the FOLFOX-4 regimen statistically significant exacerbation that increased with the number of chemotherapy cycles administered; this was more common and more severe in women. Paresthesia was also revealed to be a neurotoxic effect of the FOLFOX-4 regimen after termination of therapy. A statistically significant relationship was observed between the use of vitamin supplements and the incidence and severity of the toxicity of the FOLFOX-4 regimen. Conclusions. The findings of the current study regarding the toxicity of the FOLFOX-4 and CLF-1 therapy regimens should be taken into consideration when monitoring chemotherapy safety in colon cancer. The patients' tolerance of the administered medication and the side effects reported by patients should be constantly evaluated, which will help prevent these side effects, apply appropriate therapy and contribute to the improvement of the patients' quality of life. The functioning of the central nervous system should be carefully evaluated when planning the anticancer therapy, especially if repeated administration of neurotoxic drugs is necessary in cases of a recurrence of the disease. Chemotherapy should be thoroughly monitored for safety, especially in women over 65 years of age suffering from coexisting diseases. Colon cancer patients and their families should be informed of the risks of nutritional supplements before the start of the anticancer chemotherapy, and may need to dispense with their use (Adv Clin Exp Med 2015, 24, 1, 103-111).

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“…Até que ponto a neurotoxicidade influencia na qualidade de vida ainda não está claro, em virtude das conclusões inconsistentes de alguns estudos 2,6,9 . Porém, pacientes que evoluem com incapacidade funcional relatam dificuldade na realização de atividades de vida diária relacionadas à coordenação motora fina, como abotoar camisas, escrever ou segurar objetos 17,18,31,32 . Embora menos citado nos artigos selecionados, talvez pela não aplicação de exames neurológicos específi-cos, a diminuição ou ausência de percepção vibratória foi um dos resultados encontrados no presente estudo.…”

Section: Discussionunclassified

Neuropatia Periférica em Pacientes com Câncer Colorretal em Tratamento com Oxaliplatina

Mathias

Machado

Rodrigues

2013

RNC

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Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin

Abstract: This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.

Cited by 50 publications

References 24 publications

Oxaliplatin-Induced Lhermitte’s Phenomenon as a Manifestation of Severe Generalized Neurotoxicity

Oxaliplatin-Induced Lhermitte’s Phenomenon as a Manifestation of Severe Generalized Neurotoxicity

Evaluation of the Toxicity of Anticancer Chemotherapy in Patients with Colon Cancer

Neuropatia Periférica em Pacientes com Câncer Colorretal em Tratamento com Oxaliplatina

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