Long-term administration and efficacy of oxaliplatin with no neurotoxicity in a patient with rectal cancer: Association between neurotoxicity and the GSTP1 polymorphism

Abstract

Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients’ quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m2 without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.

The Role of Neutrophil-to-lymphocyte Ratio on the Effect of CRT for Patients With Rectal Cancer

“…Based on the results of this study, a high post-CRT NLR might be utilized as a predictor for more advanced disease features. Accordingly, patients with high NLR might be considered for adjuvant treatment (34,35). In conclusion, the findings of this study suggest that the NLR could be an important predictive factor of the response to CRT and the prognosis for patients with lower RC after surgery.…”

Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer

“…Based on our results, elevated NLR may be used as a predictor for advanced disease features. Accordingly, patients with elevated pretreatment NLR may be considered for more aggressive preoperative or adjuvant treatment [ 32 , 33 ].…”

Single nucleotide polymorphism of GSTP1 and pathological complete response in locally advanced rectal cancer patients treated with neoadjuvant concomitant radiochemotherapy

“…The demonstration of differential effects of the two alleles is therefore translated in a differential outcome for heterozygous gene (GA), as compared to the homozygous. The correlation between GSTP1 (A313G) and a higher predisposition to develop rectal cancer has been reported [ 24 , 25 ], as well as a correlation with an intensified radiochemotherapy and toxicity [ 13 , 26 ]. The results regarding a possible correlation between GSTP1 (A313G) and the outcome after radiotherapy or radiochemotherapy in many tumours are controversial [ 27 - 30 ].…”

“…On the other hand, our series underwent homogeneous treatment and the results were analyzed after long-term follow-up. Furthermore, our patients were not treated with oxaliplatin, used in some trials in combination with fluoropyrimidine, a possible confounding factor due to the known metabolic correlation with GST -genes family [ 26 , 35 ].…”